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Picazo RA, Rojo C, Rodriguez-Quiros J, González-Gil A. Current Advances in Mesenchymal Stem Cell Therapies Applied to Wounds and Skin, Eye, and Neuromuscular Diseases in Companion Animals. Animals (Basel) 2024; 14:1363. [PMID: 38731367 PMCID: PMC11083242 DOI: 10.3390/ani14091363] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2024] [Revised: 04/27/2024] [Accepted: 04/30/2024] [Indexed: 05/13/2024] Open
Abstract
Mesenchymal stem cells (MSCs) are considered a very promising alternative tool in cell therapies and regenerative medicine due to their ease of obtaining from various tissues and their ability to differentiate into different cell types. This manuscript provides a review of current knowledge on the use of MSC-based therapies as an alternative for certain common pathologies in dogs and cats where conventional treatments are ineffective. The aim of this review is to assist clinical veterinarians in making decisions about the suitability of each protocol from a clinical perspective, rather than focusing solely on research. MSC-based therapies have shown promising results in certain pathologies, such as spinal cord injuries, wounds, and skin and eye diseases. However, the effectiveness of these cell therapies can be influenced by a wide array of factors, leading to varying outcomes. Future research will focus on designing protocols and methodologies that allow more precise and effective MSC treatments for each case.
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Affiliation(s)
- Rosa Ana Picazo
- Department of Physiology, School of Veterinary Medicine, Complutense University of Madrid, 28040 Madrid, Spain;
| | - Concepción Rojo
- Department of Anatomy and Embryology, School of Veterinary Medicine, University Complutense of Madrid, 28040 Madrid, Spain;
| | - Jesus Rodriguez-Quiros
- Department of Animal Medicine and Surgery, School of Veterinary Medicine, Complutense University of Madrid, 28040 Madrid, Spain;
| | - Alfredo González-Gil
- Department of Physiology, School of Veterinary Medicine, Complutense University of Madrid, 28040 Madrid, Spain;
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Ferreira-Baptista C, Ferreira R, Fernandes MH, Gomes PS, Colaço B. Influence of the Anatomical Site on Adipose Tissue-Derived Stromal Cells' Biological Profile and Osteogenic Potential in Companion Animals. Vet Sci 2023; 10:673. [PMID: 38133224 PMCID: PMC10747344 DOI: 10.3390/vetsci10120673] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Revised: 11/13/2023] [Accepted: 11/20/2023] [Indexed: 12/23/2023] Open
Abstract
Adipose tissue-derived stromal cells (ADSCs) have generated considerable interest in the field of veterinary medicine, particularly for their potential in therapeutic strategies focused on bone regeneration. These cells possess unique biological characteristics, including their regenerative capacity and their ability to produce bioactive molecules. However, it is crucial to recognize that the characteristics of ADSCs can vary depending on the animal species and the site from which they are derived, such as the subcutaneous and visceral regions (SCAT and VAT, respectively). Thus, the present work aimed to comprehensively review the different traits of ADSCs isolated from diverse anatomical sites in companion animals, i.e., dogs, cats, and horses, in terms of immunophenotype, morphology, proliferation, and osteogenic differentiation potential. The findings indicate that the immunophenotype, proliferation, and osteogenic potential of ADSCs differ according to tissue origin and species. Generally, the proliferation rate is higher in VAT-derived ADSCs in dogs and horses, whereas in cats, the proliferation rate appears to be similar in both cells isolated from SCAT and VAT regions. In terms of osteogenic differentiation potential, VAT-derived ADSCs demonstrate the highest capability in cats, whereas SCAT-derived ADSCs exhibit superior potential in horses. Interestingly, in dogs, VAT-derived cells appear to have greater potential than those isolated from SCAT. Within the VAT, ADSCs derived from the falciform ligament and omentum show increased osteogenic potential, compared to cells isolated from other anatomical locations. Consequently, considering these disparities, optimizing isolation protocols becomes pivotal, tailoring them to the specific target species and therapeutic aims, and judiciously selecting the anatomical site for ADSC isolation. This approach holds promise to enhance the efficacy of ADSCs-based bone regenerative therapies.
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Affiliation(s)
- Carla Ferreira-Baptista
- Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of Trás-os-Montes e Alto Douro (UTAD), 5000-801 Vila Real, Portugal;
- BoneLab—Laboratory for Bone Metabolism and Regeneration, Faculty of Dental Medicine, University of Porto, 4200-393 Porto, Portugal; (M.H.F.); (P.S.G.)
- REQUIMTE/LAQV, University of Porto, 4100-007 Porto, Portugal
- REQUIMTE/LAQV, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal;
| | - Rita Ferreira
- REQUIMTE/LAQV, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal;
| | - Maria Helena Fernandes
- BoneLab—Laboratory for Bone Metabolism and Regeneration, Faculty of Dental Medicine, University of Porto, 4200-393 Porto, Portugal; (M.H.F.); (P.S.G.)
- REQUIMTE/LAQV, University of Porto, 4100-007 Porto, Portugal
| | - Pedro Sousa Gomes
- BoneLab—Laboratory for Bone Metabolism and Regeneration, Faculty of Dental Medicine, University of Porto, 4200-393 Porto, Portugal; (M.H.F.); (P.S.G.)
- REQUIMTE/LAQV, University of Porto, 4100-007 Porto, Portugal
| | - Bruno Colaço
- Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of Trás-os-Montes e Alto Douro (UTAD), 5000-801 Vila Real, Portugal;
- REQUIMTE/LAQV, University of Porto, 4100-007 Porto, Portugal
- CECAV—Animal and Veterinary Research Centre UTAD, University of Trás-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal
- Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), 5000-801 Vila Real, Portugal
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Baouche M, Ochota M, Locatelli Y, Mermillod P, Niżański W. Mesenchymal Stem Cells: Generalities and Clinical Significance in Feline and Canine Medicine. Animals (Basel) 2023; 13:1903. [PMID: 37370414 DOI: 10.3390/ani13121903] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2023] [Revised: 05/29/2023] [Accepted: 06/02/2023] [Indexed: 06/29/2023] Open
Abstract
Mesenchymal stem cells (MSCs) are multipotent cells: they can proliferate like undifferentiated cells and have the ability to differentiate into different types of cells. A considerable amount of research focuses on the potential therapeutic benefits of MSCs, such as cell therapy or tissue regeneration, and MSCs are considered powerful tools in veterinary regenerative medicine. They are the leading type of adult stem cells in clinical trials owing to their immunosuppressive, immunomodulatory, and anti-inflammatory properties, as well as their low teratogenic risk compared with pluripotent stem cells. The present review details the current understanding of the fundamental biology of MSCs. We focus on MSCs' properties and their characteristics with the goal of providing an overview of therapeutic innovations based on MSCs in canines and felines.
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Affiliation(s)
- Meriem Baouche
- Department of Reproduction and Clinic of Farm Animals, Wrocław University of Environmental and Life Sciences, 50-366 Wrocław, Poland
| | - Małgorzata Ochota
- Department of Reproduction and Clinic of Farm Animals, Wrocław University of Environmental and Life Sciences, 50-366 Wrocław, Poland
| | - Yann Locatelli
- Physiology of Reproduction and Behaviors (PRC), UMR085, INRAE, CNRS, University of Tours, 37380 Nouzilly, France
- Museum National d'Histoire Naturelle, Réserve Zoologique de la Haute Touche, 36290 Obterre, France
| | - Pascal Mermillod
- Physiology of Reproduction and Behaviors (PRC), UMR085, INRAE, CNRS, University of Tours, 37380 Nouzilly, France
| | - Wojciech Niżański
- Department of Reproduction and Clinic of Farm Animals, Wrocław University of Environmental and Life Sciences, 50-366 Wrocław, Poland
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Herrera D, Lodoso-Torrecilla I, Ginebra MP, Rappe K, Franch J. Osteogenic differentiation of adipose-derived canine mesenchymal stem cells seeded in porous calcium-phosphate scaffolds. Front Vet Sci 2023; 10:1149413. [PMID: 37332740 PMCID: PMC10272761 DOI: 10.3389/fvets.2023.1149413] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2023] [Accepted: 04/27/2023] [Indexed: 06/20/2023] Open
Abstract
Introduction Engineered bone graft substitutes are a promising alternative and supplement to autologous bone grafts as treatments for bone healing impairment. Advances in human medicine extend an invitation to pursue these biomimetic strategies in animal patients, substantiated by the theory that specialized scaffolds, multipotent cells, and biological cues may be combined into a bioactive implant intended for the enhancement of tissue regeneration. Methods This proof-of-concept study was designed to evaluate and validate the feasibility of beta-tricalcium phosphate foam scaffolds seeded with canine mesenchymal stem cells derived from adipose tissue. Cell-inoculated samples and sham controls were cultured statically for 72 hours in complete growth medium to evaluate seeding capacity, while a subset of loaded scaffolds was further induced with osteogenic culture medium for 21 days. Produced implants were characterized and validated with a combination of immunofluorescence and reflection confocal microscopy, scanning electron microscopy, and polymerase chain reaction to confirm osteogenic differentiation in tridimensional-induced samples. Results After 72 hours of culture, all inoculated scaffolds presented widespread yet heterogeneous surface seeding, distinctively congregating stem cells around pore openings. Furthermore, at 21 days of osteogenic culture conditions, robust osteoblastic differentiation of the seeded cells was confirmed by the change of cell morphology and evident deposition of extra-cellular matrix, accompanied by mineralization and scaffold remodeling; furthermore, all induced cell-loaded implants lost specific stemness immunophenotype expression and simultaneously upregulated genomic expression of osteogenic genes Osterix and Ostecalcin. Conclusions β-TCP bio-ceramic foam scaffolds proved to be suitable carriers and hosts of canine adipose-derived MSCs, promoting not only surface attachment and proliferation, but also demonstrating strong in-vitro osteogenic potential. Although this research provides satisfactory in-vitro validation for the conceptualization and feasibility of a canine bio-active bone implant, further testing such as patient safety, large-scale reproducibility, and quality assessment are needed for regulatory compliance in future commercial clinical applications.
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Affiliation(s)
- David Herrera
- Bone Regeneration Research Group, Department of Animal Medicine and Surgery, Veterinary Faculty, Autonomous University of Barcelona, Cerdanyola del Vallès, Spain
| | - Irene Lodoso-Torrecilla
- Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Engineering, Universitat Politècnica de Catalunya, Barcelona, Spain
| | - Maria-Pau Ginebra
- Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Engineering, Universitat Politècnica de Catalunya, Barcelona, Spain
| | - Katrin Rappe
- Bone Regeneration Research Group, Department of Animal Medicine and Surgery, Veterinary Faculty, Autonomous University of Barcelona, Cerdanyola del Vallès, Spain
| | - Jordi Franch
- Bone Regeneration Research Group, Department of Animal Medicine and Surgery, Veterinary Faculty, Autonomous University of Barcelona, Cerdanyola del Vallès, Spain
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Thoene M, Bejer-Olenska E, Wojtkiewicz J. The Current State of Osteoarthritis Treatment Options Using Stem Cells for Regenerative Therapy: A Review. Int J Mol Sci 2023; 24:ijms24108925. [PMID: 37240271 DOI: 10.3390/ijms24108925] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Revised: 04/27/2023] [Accepted: 05/16/2023] [Indexed: 05/28/2023] Open
Abstract
Articular cartilage has very low metabolic activity. While minor injuries may be spontaneously repaired within the joint by chondrocytes, there is very little chance of a severely impaired joint regenerating itself when damaged. Therefore, any significant joint injury has little chance of spontaneously healing without some type of therapy. This article is a review that will examine the causes of osteoarthritis, both acute and chronic, and how it may be treated using traditional methods as well as with the latest stem cell technology. The latest regenerative therapy is discussed, including the use and potential risks of mesenchymal stem cells for tissue regeneration and implantation. Applications are then discussed for the treatment of OA in humans after using canine animal models. Since the most successful research models of OA were dogs, the first applications for treatment were veterinary. However, the treatment options have now advanced to the point where patients suffering from osteoarthritis may be treated with this technology. A survey of the literature was performed in order to determine the current state of stem cell technology being used in the treatment of osteoarthritis. Then, the stem cell technology was compared with traditional treatment options.
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Affiliation(s)
- Michael Thoene
- Department of Medical Biology, School of Public Health, University of Warmia and Mazury in Olsztyn, 10-561 Olsztyn, Poland
| | - Ewa Bejer-Olenska
- Department of Pathophysiology, School of Medicine, University of Warmia and Mazury in Olsztyn, 10-082 Olsztyn, Poland
| | - Joanna Wojtkiewicz
- Department of Pathophysiology, School of Medicine, University of Warmia and Mazury in Olsztyn, 10-082 Olsztyn, Poland
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Stage HJ, Trappe S, Söllig K, Trachsel DS, Kirsch K, Zieger C, Merle R, Aschenbach JR, Gehlen H. Multilineage Differentiation Potential of Equine Adipose-Derived Stromal/Stem Cells from Different Sources. Animals (Basel) 2023; 13:ani13081352. [PMID: 37106915 PMCID: PMC10135324 DOI: 10.3390/ani13081352] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2023] [Revised: 04/06/2023] [Accepted: 04/13/2023] [Indexed: 04/29/2023] Open
Abstract
The investigation of multipotent stem/stromal cells (MSCs) in vitro represents an important basis for translational studies in large animal models. The study's aim was to examine and compare clinically relevant in vitro properties of equine MSCs, which were isolated from abdominal (abd), retrobulbar (rb) and subcutaneous (sc) adipose tissue by collagenase digestion (ASCs-SVF) and an explant technique (ASCs-EXP). Firstly, we examined proliferation and trilineage differentiation and, secondly, the cardiomyogenic differentiation potential using activin A, bone morphogenetic protein-4 and Dickkopf-1. Fibroblast-like, plastic-adherent ASCs-SVF and ASCs-EXP were obtained from all sources. The proliferation and chondrogenic differentiation potential did not differ significantly between the isolation methods and localizations. However, abd-ASCs-EXP showed the highest adipogenic differentiation potential compared to rb- and sc-ASCs-EXP on day 7 and abd-ASCs-SVF a higher adipogenic potential compared to abd-ASCs-EXP on day 14. Osteogenic differentiation potential was comparable at day 14, but by day 21, abd-ASCs-EXP demonstrated a higher osteogenic potential compared to abd-ASCs-SVF and rb-ASCs-EXP. Cardiomyogenic differentiation could not be achieved. This study provides insight into the proliferation and multilineage differentiation potential of equine ASCs and is expected to provide a basis for future preclinical and clinical studies in horses.
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Affiliation(s)
- Hannah J Stage
- Equine Clinic, Surgery and Radiology, Department of Veterinary Medicine, Freie Universität Berlin, Oertzenweg 19b, 14163 Berlin, Germany
| | - Susanne Trappe
- Institute of Veterinary Physiology, Freie Universität Berlin, Oertzenweg 19b, 14163 Berlin, Germany
| | - Katharina Söllig
- Institute of Veterinary Physiology, Freie Universität Berlin, Oertzenweg 19b, 14163 Berlin, Germany
| | - Dagmar S Trachsel
- Clinical Unit of Equine Internal Medicine, Department for Companion Animals and Horses, University of Veterinary Medicine Vienna, Veterinärplatz 1, 1210 Vienna, Austria
| | - Katharina Kirsch
- Institute of Veterinary Physiology, Freie Universität Berlin, Oertzenweg 19b, 14163 Berlin, Germany
| | - Cornelia Zieger
- Institute of Veterinary Pathology Department of Veterinary Medicine, Freie Universität Berlin, Robert-von-Ostertag-Straße 15, 14163 Berlin, Germany
| | - Roswitha Merle
- Institute for Veterinary Epidemiology and Biostatistics, Department of Veterinary Medicine, Freie Universität Berlin, Königsweg 67, 14163 Berlin, Germany
| | - Jörg R Aschenbach
- Institute of Veterinary Physiology, Freie Universität Berlin, Oertzenweg 19b, 14163 Berlin, Germany
| | - Heidrun Gehlen
- Equine Clinic, Surgery and Radiology, Department of Veterinary Medicine, Freie Universität Berlin, Oertzenweg 19b, 14163 Berlin, Germany
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Kumar S, Lahiri C, Chaaudhary S, Paul P, Verma YK. Design, development and characterisation of an optimised scaffold to enhance cell proliferation for tissue repair. J Microencapsul 2023; 40:82-97. [PMID: 36719352 DOI: 10.1080/02652048.2023.2175922] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
Scaffolds are implanted to spur the regeneration of damaged tissues. The inappropriate construction of scaffolds laden with cells is not efficient. The optimisation of the scaffolds' constituents is essential for tissue repair. In this study, a scaffold embedded with Raloxifene drug was optimised via Response Surface Methodology (RSM), targeting controlled cell proliferation. The independent variables for RSM (fibronectin, collagen I, glutaraldehyde, and Raloxifene) were screened in Swiss target prediction software (probability ≥99%) to optimise dependent variables (porosity, cell viability, degradation, and swelling) by ANOVA and characterised with FTIR, SEM and contact angle measurement. The scaffold was tested for antimicrobial property, and proliferation and attachment of mouse mesenchymal stem cells. The ANOVA analysis with p value ≤ 0.0001 suggested the optimal concentration of biomaterials and drugs. The optimised scaffold displayed 80% porosity with pore size 33 ± 3 µm. We also observed significant cell attachment and proliferation (p value ≤ 0.05) in optimised scaffold. The scaffold may be further evaluated for its potential for tissue repair.
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Affiliation(s)
- Subodh Kumar
- Stem Cell and Tissue Engineering Research Group, Institute of Nuclear Medicine & Allied Sciences (INMAS), Defence Research and Development Organisation (DRDO), Lucknow Road, Timarpur, Delhi 110054, India
| | - Chanakya Lahiri
- Stem Cell and Tissue Engineering Research Group, Institute of Nuclear Medicine & Allied Sciences (INMAS), Defence Research and Development Organisation (DRDO), Lucknow Road, Timarpur, Delhi 110054, India
| | - Somya Chaaudhary
- Stem Cell and Tissue Engineering Research Group, Institute of Nuclear Medicine & Allied Sciences (INMAS), Defence Research and Development Organisation (DRDO), Lucknow Road, Timarpur, Delhi 110054, India
| | - Prateek Paul
- Stem Cell and Tissue Engineering Research Group, Institute of Nuclear Medicine & Allied Sciences (INMAS), Defence Research and Development Organisation (DRDO), Lucknow Road, Timarpur, Delhi 110054, India
| | - Yogesh Kumar Verma
- Stem Cell and Tissue Engineering Research Group, Institute of Nuclear Medicine & Allied Sciences (INMAS), Defence Research and Development Organisation (DRDO), Lucknow Road, Timarpur, Delhi 110054, India
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The Osteogenic Potential of Falciform Ligament-Derived Stromal Cells-A Comparative Analysis between Two Osteogenic Induction Programs. BIOENGINEERING (BASEL, SWITZERLAND) 2022; 9:bioengineering9120810. [PMID: 36551016 PMCID: PMC9774535 DOI: 10.3390/bioengineering9120810] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/05/2022] [Revised: 11/28/2022] [Accepted: 12/13/2022] [Indexed: 12/23/2022]
Abstract
Mesenchymal stromal cells (MSCs) have gained special relevance in bone tissue regenerative applications. MSCs have been isolated from different depots, with adipose tissue being acknowledged as one of the most convenient sources, given the wide availability, high cellular yield, and obtainability. Recently, the falciform ligament (FL) has been regarded as a potential depot for adipose tissue-derived stromal cells (FL-ADSCs) isolation. Nonetheless, the osteogenic capability of FL-ADSCs has not been previously characterized. Thus, the present study aimed the detailed characterization of FL-ADSCs' functionality upon osteogenic induction through a classic (dexamethasone-based-DEX) or an innovative strategy with retinoic acid (RA) in a comparative approach with ADSCs from a control visceral region. Cultures were characterized for cell proliferation, metabolic activity, cellular morphology, fluorescent cytoskeletal and mitochondrial organization, and osteogenic activity-gene expression analysis and cytochemical staining. FL-derived populations expressed significantly higher levels of osteogenic genes and cytochemical markers, particularly with DEX induction, as compared to control ADSCs that were more responsive to RA. FL-ADSCs were identified as a potential source for bone regenerative applications, given the heightened osteogenic functionality. Furthermore, data highlighted the importance of the selection of the most adequate osteogenic-inducing program concerning the specificities of the basal cell population.
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Wang DH, Chen JS, Hou R, Li Y, An JH, He P, Cai ZG, Liang XH, Liu YL. Comparison of transcriptome profiles of mesenchymal stem cells derived from umbilical cord and bone marrow of giant panda (Ailuropoda melanoleuca). Gene X 2022; 845:146854. [DOI: 10.1016/j.gene.2022.146854] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2022] [Revised: 08/15/2022] [Accepted: 08/26/2022] [Indexed: 11/28/2022] Open
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Huang Y, Zhu M, Liu Z, Hu R, Li F, Song Y, Geng Y, Ma W, Song K, Zhang M. Bone marrow mesenchymal stem cells in premature ovarian failure: Mechanisms and prospects. Front Immunol 2022; 13:997808. [PMID: 36389844 PMCID: PMC9646528 DOI: 10.3389/fimmu.2022.997808] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Accepted: 10/17/2022] [Indexed: 12/31/2022] Open
Abstract
Premature ovarian failure (POF) is a common female reproductive disorder and characterized by menopause, increased gonadotropin levels and estrogen deficiency before the age of 40 years old. The etiologies and pathogenesis of POF are not fully clear. At present, hormone replacement therapy (HRT) is the main treatment options for POF. It helps to ameliorate perimenopausal symptoms and related health risks, but can't restore ovarian function and fertility fundamentally. With the development of regenerative medicine, bone marrow mesenchymal stem cells (BMSCs) have shown great potential for the recovery of ovarian function and fertility based on the advantages of abundant sources, high capacity for self-renewal and differentiation, low immunogenicity and less ethical considerations. This systematic review aims to summarize the possible therapeutic mechanisms of BMSCs for POF. A detailed search strategy of preclinical studies and clinical trials on BMSCs and POF was performed on PubMed, MEDLINE, Web of Science and Embase database. A total of 21 studies were included in this review. Although the standardization of BMSCs need more explorations, there is no doubt that BMSCs transplantation may represent a prospective therapy for POF. It is hope to provide a theoretical basis for further research and treatment for POF.
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Affiliation(s)
- Yanjing Huang
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Mengdi Zhu
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Zhuo Liu
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Runan Hu
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Fan Li
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Yufan Song
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Yuli Geng
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Wenwen Ma
- Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Kunkun Song
- Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China,*Correspondence: Mingmin Zhang, ; Kunkun Song,
| | - Mingmin Zhang
- Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China,*Correspondence: Mingmin Zhang, ; Kunkun Song,
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Lee SK, Jung SH, Song SJ, Lee IG, Choi JY, Zadeh H, Lee DW, Pi SH, You HK. miRNA-Based Early Healing Mechanism of Extraction Sockets: miR-190a-5p, a Potential Enhancer of Bone Healing. BIOMED RESEARCH INTERNATIONAL 2022; 2022:7194640. [PMID: 36317115 PMCID: PMC9617701 DOI: 10.1155/2022/7194640] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/04/2022] [Revised: 09/13/2022] [Accepted: 10/08/2022] [Indexed: 09/07/2024]
Abstract
Objective Tooth extraction causes a wound with hard and soft tissue defects in the alveolar ridge. Few studies have reported the function of microRNAs (miRNAs) in the healing of extraction sockets. This study used bioinformatics analysis to reveal the possible relevance and role of miRNAs during the early stages following tooth extraction. Materials and Methods Socket tissues from beagle dogs (Canis familiaris; two males and two females) were collected 1 and 12 hours after extraction of premolars on both sides of the mandible. miRNA expression was profiled through miRNA sequencing, and hub miRNAs showing characteristic expression patterns were selected and subjected to target enrichment analysis. Alkaline phosphatase (ALP) activity analysis and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were performed to verify the effect of hub miRNA on osteoblast differentiation and bone regeneration in vivo. Results Five miRNAs were identified to have consistently high expression levels, with cfa-miR-451 showing the highest expression. Additionally, 20 hub miRNAs were selected as candidates expected to play an important role in the healing process. Pathways, such as the MAPK, axon guidance, TGF-β, and Wnt signaling, were significantly enriched. Among hub miRNAs, miR-190a-5p increased ALP activity and mRNA expression of osteogenic markers and increased new bone formation in vivo. Conclusions Our findings suggest that miRNAs may be involved in the earliest stages of socket healing after tooth extraction and can play an important role in moderating the entire socket healing mechanism in the extraction socket.
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Affiliation(s)
- Shin-Kyu Lee
- Department of Periodontology, School of Dentistry, Wonkwang University, Iksan, Jeonbuk, Republic of Korea
- Clinical Lab for Innovative Periodontology, Department of Periodontology, School of Dentistry, Wonkwang University, Iksan, Jeonbuk, Republic of Korea
| | - Su-Hyeon Jung
- Department of Periodontology, School of Dentistry, Wonkwang University, Iksan, Jeonbuk, Republic of Korea
- Clinical Lab for Innovative Periodontology, Department of Periodontology, School of Dentistry, Wonkwang University, Iksan, Jeonbuk, Republic of Korea
| | - Sang-Jin Song
- Department of Periodontology, School of Dentistry, Wonkwang University, Iksan, Jeonbuk, Republic of Korea
| | - In-Gyu Lee
- Department of Periodontology, School of Dentistry, Wonkwang University, Iksan, Jeonbuk, Republic of Korea
| | - Jae-Yoon Choi
- Department of Periodontology, School of Dentistry, Wonkwang University, Iksan, Jeonbuk, Republic of Korea
- Clinical Lab for Innovative Periodontology, Department of Periodontology, School of Dentistry, Wonkwang University, Iksan, Jeonbuk, Republic of Korea
| | - Homayoun Zadeh
- VISTA Institute for Therapeutic Innovations, Woodland Hills, CA, USA
| | - Dong-Woon Lee
- Department of Periodontology, School of Dentistry, Wonkwang University, Iksan, Jeonbuk, Republic of Korea
| | - Sung-Hee Pi
- Department of Periodontology, School of Dentistry, Wonkwang University, Iksan, Jeonbuk, Republic of Korea
| | - Hyung-Keun You
- Department of Periodontology, School of Dentistry, Wonkwang University, Iksan, Jeonbuk, Republic of Korea
- Clinical Lab for Innovative Periodontology, Department of Periodontology, School of Dentistry, Wonkwang University, Iksan, Jeonbuk, Republic of Korea
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Humenik F, Maloveska M, Hudakova N, Petrouskova P, Hornakova L, Domaniza M, Mudronova D, Bodnarova S, Cizkova D. A Comparative Study of Canine Mesenchymal Stem Cells Isolated from Different Sources. Animals (Basel) 2022; 12:1502. [PMID: 35739839 PMCID: PMC9219547 DOI: 10.3390/ani12121502] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Revised: 05/26/2022] [Accepted: 06/04/2022] [Indexed: 01/06/2023] Open
Abstract
In this study, we provide comprehensive analyses of mesenchymal stem cells (MSCs) isolated from three types of canine tissues: bone marrow (BM-MSCs), adipose tissue (AT-MSCs) and amniotic tissue (AM-MSCs). We compare their morphology, phenotype, multilineage potential and proliferation activity. The BM-MSCs and AM-MSCs showed fibroblast-like shapes against the spindle shape of the AT-MSCs. All populations showed strong osteogenic and chondrogenic potential. However, we observed phenotypic differences. The BM-MSCs and AT-MSCs revealed high expression of CD29, CD44, CD90 and CD105 positivity compared to the AM-MSCs, which showed reduced expression of all the analysed CD markers. Similarly, the isolation yield and proliferation varied depending on the source. The highest isolation yield and proliferation were detected in the population of AT-MSCs, while the AM-MSCs showed a high yield of cells, but the lowest proliferation activity, in contrast to the BM-MSCs which had the lowest isolation yield. Thus, the present data provide assumptions for obtaining a homogeneous MSC derived from all three canine tissues for possible applications in veterinary regenerative medicine, while the origin of isolated MSCs must always be taken into account.
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Affiliation(s)
- Filip Humenik
- Centre of Experimental and Clinical Regenerative Medicine, The University of Veterinary Medicine and Pharmacy in Kosice, 041 81 Kosice, Slovakia; (F.H.); (M.M.); (N.H.); (P.P.)
| | - Marcela Maloveska
- Centre of Experimental and Clinical Regenerative Medicine, The University of Veterinary Medicine and Pharmacy in Kosice, 041 81 Kosice, Slovakia; (F.H.); (M.M.); (N.H.); (P.P.)
| | - Nikola Hudakova
- Centre of Experimental and Clinical Regenerative Medicine, The University of Veterinary Medicine and Pharmacy in Kosice, 041 81 Kosice, Slovakia; (F.H.); (M.M.); (N.H.); (P.P.)
| | - Patricia Petrouskova
- Centre of Experimental and Clinical Regenerative Medicine, The University of Veterinary Medicine and Pharmacy in Kosice, 041 81 Kosice, Slovakia; (F.H.); (M.M.); (N.H.); (P.P.)
| | - Lubica Hornakova
- University Veterinary Hospital, The University of Veterinary Medicine and Pharmacy in Kosice, 041 81 Kosice, Slovakia; (L.H.); (M.D.)
| | - Michal Domaniza
- University Veterinary Hospital, The University of Veterinary Medicine and Pharmacy in Kosice, 041 81 Kosice, Slovakia; (L.H.); (M.D.)
| | - Dagmar Mudronova
- Institute of Microbiology and Immunology, The University of Veterinary Medicine and Pharmacy in Kosice, 041 81 Kosice, Slovakia;
| | - Simona Bodnarova
- Department of Pneumology a Phtiseology, Faculty of Medicine, University of Pavol Jozef Safarik, 041 80 Kosice, Slovakia;
| | - Dasa Cizkova
- Centre of Experimental and Clinical Regenerative Medicine, The University of Veterinary Medicine and Pharmacy in Kosice, 041 81 Kosice, Slovakia; (F.H.); (M.M.); (N.H.); (P.P.)
- Institute of Neuroimmunology, Slovak Academy of Sciences, 845 10 Bratislava, Slovakia
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MacIver MA, Dobson LK, Gregory CA, Muneoka K, Saunders WB. A three-dimensional (3D), serum-free, Collagen Type I system for chondrogenesis of canine bone marrow-derived multipotent stromal cells (cMSCs). PLoS One 2022; 17:e0269571. [PMID: 35679245 PMCID: PMC9182251 DOI: 10.1371/journal.pone.0269571] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Accepted: 05/19/2022] [Indexed: 12/03/2022] Open
Abstract
The dog is an underrepresented large animal translational model for orthopedic cell-based tissue engineering. While chondrogenic differentiation of canine multipotent stromal cells (cMSCs) has been reported using the classic micromass technique, cMSCs respond inconsistently to this method. The objectives of this study were to develop a three-dimensional (3D), serum-free, Collagen Type I system to facilitate cMSC chondrogenesis and, once established, to determine the effect of chondrogenic growth factors on cMSC chondrogenesis. Canine MSCs were polymerized in 100 μL Collagen Type I gels (5 mg/mL) at 1 x 106 cells/construct. Constructs were assessed using morphometry, live/dead staining, and histology in 10 various chondrogenic media. Four media were selected for additional in-depth analyses via lactate dehydrogenase release, total glycosaminoglycan content, qPCR (COL1A1, COL2A, SOX9, ACAN, BGLAP and SP7), immunofluorescence, and TUNEL staining. In the presence of dexamethasone and transforming growth factor-β3 (TGF-β3), both bone morphogenic protein-2 (BMP-2) and basic fibroblast growth factor (bFGF) generated larger chondrogenic constructs, although BMP-2 was required to achieve histologic characteristics of chondrocytes. Chondrogenic medium containing dexamethasone, TGF-β3, BMP-2 and bFGF led to a significant decrease in lactate dehydrogenase release at day 3 and glycosaminoglycan content was significantly increased in these constructs at day 3, 10, and 21. Both osteogenic and chondrogenic transcripts were induced in response to dexamethasone, TGF-β3, BMP-2 and bFGF. Collagen Type II and X were detected in all groups via immunofluorescence. Finally, TUNEL staining was positive in constructs lacking BMP-2 or bFGF. In conclusion, the 3D, serum-free, Collagen Type-I assay described herein proved useful in assessing cMSC differentiation and will serve as a productive system to characterize cMSCs or to fabricate tissue engineering constructs for clinical use.
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Affiliation(s)
- Melissa A. MacIver
- Department of Small Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas, United States of America
| | - Lauren K. Dobson
- Department of Small Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas, United States of America
| | - Carl A. Gregory
- Department of Molecular and Cellular Medicine, Texas A&M College of Medicine, Texas A&M University, College Station, Texas, United States of America
| | - Ken Muneoka
- Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas, United States of America
| | - W. Brian Saunders
- Department of Small Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas, United States of America
- * E-mail:
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14
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Kim SY, Yoon TH, Na J, Yi SJ, Jin Y, Kim M, Oh TH, Chung TW. Mesenchymal Stem Cells and Extracellular Vesicles Derived from Canine Adipose Tissue Ameliorates Inflammation, Skin Barrier Function and Pruritus by Reducing JAK/STAT Signaling in Atopic Dermatitis. Int J Mol Sci 2022; 23:ijms23094868. [PMID: 35563259 PMCID: PMC9101369 DOI: 10.3390/ijms23094868] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Revised: 04/22/2022] [Accepted: 04/25/2022] [Indexed: 02/01/2023] Open
Abstract
Canine atopic dermatitis (AD) is a common chronic inflammatory skin disorder resulting from imbalance between T lymphocytes. Current canine AD treatments use immunomodulatory drugs, but some of the dogs have limitations that do not respond to standard treatment, or relapse after a period of time. Thus, the purpose of this study was to evaluate the immunomodulatory effect of mesenchymal stem cells derived from canine adipose tissue (cASCs) and cASCs-derived extracellular vesicles (cASC-EVs) on AD. First, we isolated and characterized cASCs and cASCs-EVs to use for the improvement of canine atopic dermatitis. Here, we investigated the effect of cASCs or cASC-EVs on DNCB-induced AD in mice, before using for canine AD. Interestingly, we found that cASCs and cASC-EVs improved AD-like dermatitis, and markedly decreased levels of serum IgE, (49.6%, p = 0.002 and 32.1%, p = 0.016 respectively) epidermal inflammatory cytokines and chemokines, such as IL-4 (32%, p = 0.197 and 44%, p = 0.094 respectively), IL-13 (47.4%, p = 0.163, and 50.0%, p = 0.039 respectively), IL-31 (64.3%, p = 0.030 and 76.2%, p = 0.016 respectively), RANTES (66.7%, p = 0.002 and 55.6%, p = 0.007) and TARC (64%, p = 0.016 and 86%, p = 0.010 respectively). In addition, cASCs or cASC-EVs promoted skin barrier repair by restoring transepidermal water loss, enhancing stratum corneum hydration and upregulating the expression levels of epidermal differentiation proteins. Moreover, cASCs or cASC-EVs reduced IL-31/TRPA1-mediated pruritus and activation of JAK/STAT signaling pathway. Taken together, these results suggest the potential of cASCs or cASC-EVs for the treatment of chronic inflammation and damaged skin barrier in AD or canine AD.
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Affiliation(s)
- Sung Youl Kim
- GNG CELL Co., Ltd., R&D Center, 122 Unjung-ro, Bundang-gu, Seongnam-si 13466, Korea; (S.Y.K.); (T.H.Y.)
| | - Tae Hong Yoon
- GNG CELL Co., Ltd., R&D Center, 122 Unjung-ro, Bundang-gu, Seongnam-si 13466, Korea; (S.Y.K.); (T.H.Y.)
| | - Jungtae Na
- Department of Life Science, Sogang University, 35 Baekbeom-ro, Mapo-gu, Seoul 04107, Korea;
| | - Seong Joon Yi
- Department of Veterinary Anatomy, College of Veterinary Medicine, Kyungpook National University, 80 Daehak-ro, Buk-gu, Daegu 41566, Korea;
| | - Yunseok Jin
- Department of Veterinary Internal Medicine, College of Veterinary Medicine, Kyungpook National University, 80 Daehak-ro, Buk-gu, Daegu 41566, Korea; (Y.J.); (M.K.)
| | - Minji Kim
- Department of Veterinary Internal Medicine, College of Veterinary Medicine, Kyungpook National University, 80 Daehak-ro, Buk-gu, Daegu 41566, Korea; (Y.J.); (M.K.)
| | - Tae-Ho Oh
- Department of Veterinary Internal Medicine, College of Veterinary Medicine, Kyungpook National University, 80 Daehak-ro, Buk-gu, Daegu 41566, Korea; (Y.J.); (M.K.)
- Correspondence: (T.-H.O.); (T.-W.C.)
| | - Tae-Wook Chung
- JIN BioCell Co., Ltd., R&D Center, #101-103, National Clinical Research Center for Korean Medicine, Pusan National University Korean Medicine Hospital, 20 Geumo-ro, Mulgeum-eup, Yangsan-si 50612, Korea
- Correspondence: (T.-H.O.); (T.-W.C.)
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15
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Voga M, Majdic G. Articular Cartilage Regeneration in Veterinary Medicine. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2022; 1401:23-55. [DOI: 10.1007/5584_2022_717] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
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16
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Ma C, Liu Y, Ma Y, Jiang L, Huang Q, Liu G, Guo Y, Wang C, Liu C. Identification and characterization of pulmonary mesenchymal stem cells derived from rat fetal lung tissue. Tissue Cell 2021; 73:101628. [PMID: 34479072 DOI: 10.1016/j.tice.2021.101628] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Revised: 08/07/2021] [Accepted: 08/18/2021] [Indexed: 11/17/2022]
Abstract
Pulmonary mesenchymal stem cells (PMSCs) have great potential in lung tissue repair and regeneration, which have been isolated from some mammalian species, including mice, bovine and pig. However, the isolation, characteristics and differentiation potential of rat PMSCs have not been reported. In this study, we successfully isolated PMSCs from Sprague-Dawley rat fetal lung tissue in vitro for the first time and attempted to evaluate its multilineage differentiation potentials. The cultured PMSCs showed typical spindle-shaped morphology and high proliferative potential, and could be passaged for at least 13 passages and maintained high hereditary stability with more than 93.6 % of cells were diploid (2n = 42) by G-banding analysis. Furthermore, the PMSCs could express mesenchymal markers Sca-1, CD29, CD44, CD73 and CD90, but not hematopoietic markers CD34 and CD45. Besides, the expression of cell markers of AT2 (SFTPC), AT1 (PDPN) and macrophage (CD11b) were also negative. Cell cycle examination revealed majority of the PMSCs were in G0/G1 phase, which are similar with previously reported pig PMSCs. In addition, the PMSCs were multipotent and could differentiated into osteocytes, adipocytes, hepatocytes and neurons in vitro. Together, the present study demonstrated the stemness and multi-differentiation potentials of rat PMSCs, which conferred a potential regenerative cell resource for cell regenerative therapy of lung injury.
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Affiliation(s)
- Caiyun Ma
- School of Life Science, Bengbu Medical College, Bengbu, Anhui, 233030, PR China
| | - Yang Liu
- School of Life Science, Bengbu Medical College, Bengbu, Anhui, 233030, PR China
| | - Yingchun Ma
- School of Life Science, Bengbu Medical College, Bengbu, Anhui, 233030, PR China
| | - Lijie Jiang
- School of Life Science, Bengbu Medical College, Bengbu, Anhui, 233030, PR China
| | - Qianyi Huang
- School of Life Science, Bengbu Medical College, Bengbu, Anhui, 233030, PR China
| | - Gaofeng Liu
- School of Life Science, Bengbu Medical College, Bengbu, Anhui, 233030, PR China
| | - Yu Guo
- School of Life Science, Bengbu Medical College, Bengbu, Anhui, 233030, PR China
| | - Chunjing Wang
- School of Life Science, Bengbu Medical College, Bengbu, Anhui, 233030, PR China.
| | - Changqing Liu
- School of Life Science, Bengbu Medical College, Bengbu, Anhui, 233030, PR China.
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Transplantation of rat cranial bone-derived mesenchymal stem cells promotes functional recovery in rats with spinal cord injury. Sci Rep 2021; 11:21907. [PMID: 34754046 PMCID: PMC8578570 DOI: 10.1038/s41598-021-01490-1] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Accepted: 10/29/2021] [Indexed: 02/07/2023] Open
Abstract
Cell-based therapy using mesenchymal stem cells (MSCs) is a novel treatment strategy for spinal cord injury (SCI). MSCs can be isolated from various tissues, and their characteristics vary based on the source. However, reports demonstrating the effect of transplanted rat cranial bone-derived MSCs (rcMSCs) on rat SCI models are lacking. In this study, we determined the effect of transplanting rcMSCs in rat SCI models. MSCs were established from collected bone marrow and cranial bones. SCI rats were established using the weight-drop method and transplanted intravenously with MSCs at 24 h post SCI. The recovery of motor function and hindlimb electrophysiology was evaluated 4 weeks post transplantation. Electrophysiological recovery was evaluated by recording the transcranial electrical stimulation motor-evoked potentials. Tissue repair after SCI was assessed by calculating the cavity ratio. The expression of genes involved in the inflammatory response and cell death in the spinal cord tissue was assessed by real-time polymerase chain reaction. The transplantation of rcMSCs improved motor function and electrophysiology recovery, and reduced cavity ratio. The expression of proinflammatory cytokines was suppressed in the spinal cord tissues of the rats that received rcMSCs. These results demonstrate the efficacy of rcMSCs as cell-based therapy for SCI.
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18
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Benavides FP, Pinto GBA, Heckler MCT, Hurtado DMR, Teixeira LR, Monobe MMDS, Machado GF, de Melo GD, Rodríguez-Sánchez DN, Alvarenga FDCLE, Amorim RM. Intrathecal Transplantation of Autologous and Allogeneic Bone Marrow-Derived Mesenchymal Stem Cells in Dogs. Cell Transplant 2021; 30:9636897211034464. [PMID: 34427495 PMCID: PMC8388229 DOI: 10.1177/09636897211034464] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
The route used in the transplantation of mesenchymal stem cells (MSCs) can directly affect the treatment success. The transplantation of MSCs via the intrathecal (IT) route can be an important therapeutic strategy for neurological disorders. The objective of this study was to evaluate the safety and feasibility of the IT transplantation of autologous (Auto-MSCs) and allogeneic (Allo-MSCs) bone marrow mesenchymal stem cells (BM-MSCs) in healthy dogs. Based on neurodisability score, cerebrospinal fluid (CSF) and magnetic resonance imaging (MRI), no significant differences from the control group were observed on day 1 or day 5 after IT Auto- or Allo-MSCs transplantation (P > 0.05). In addition, analysis of matrix metalloproteinase (MMP)-2 and MMP-9 expression in the CSF revealed no significant differences (P > 0.05) at 5 days after IT transplantation in the Auto- or Allo-MSCs group when compared to the control. Intrathecal transplantation of BM-MSCs in dogs provides a safe, easy and minimally invasive route for the use of cell-based therapeutics in central nervous system diseases.
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Affiliation(s)
- Felipe Pérez Benavides
- Department of Veterinary Clinics, School of Veterinary Medicine and Animal Science, São Paulo State University (UNESP), 18618-681-Botucatu, SP, Brazil
| | - Giovana Boff Araujo Pinto
- Department of Veterinary Clinics, School of Veterinary Medicine and Animal Science, São Paulo State University (UNESP), 18618-681-Botucatu, SP, Brazil
| | - Marta Cristina Thomas Heckler
- Department of Veterinary Clinics, School of Veterinary Medicine and Animal Science, São Paulo State University (UNESP), 18618-681-Botucatu, SP, Brazil
| | - Diana Milena Rodríguez Hurtado
- Department of Animal Reproduction and Veterinary Radiology, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil
| | - Livia Ramos Teixeira
- Department of Veterinary Surgery and Anesthesiology, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil
| | - Marina Mitie de Souza Monobe
- Department of Veterinary Clinics, School of Veterinary Medicine and Animal Science, São Paulo State University (UNESP), 18618-681-Botucatu, SP, Brazil
| | - Gisele Fabrino Machado
- Department of Clinics, Surgery and Animal Reproduction, São Paulo State University (UNESP), Araçatuba, São Paulo, Brazil
| | - Guilherme Dias de Melo
- Department of Clinics, Surgery and Animal Reproduction, São Paulo State University (UNESP), Araçatuba, São Paulo, Brazil
| | - Diego Noé Rodríguez-Sánchez
- Department of Veterinary Clinics, School of Veterinary Medicine and Animal Science, São Paulo State University (UNESP), 18618-681-Botucatu, SP, Brazil
| | | | - Rogério Martins Amorim
- Department of Veterinary Clinics, School of Veterinary Medicine and Animal Science, São Paulo State University (UNESP), 18618-681-Botucatu, SP, Brazil
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Rodríguez-Sánchez DN, Pinto GBA, Cartarozzi LP, de Oliveira ALR, Bovolato ALC, de Carvalho M, da Silva JVL, Dernowsek JDA, Golim M, Barraviera B, Ferreira RS, Deffune E, Bertanha M, Amorim RM. 3D-printed nerve guidance conduits multi-functionalized with canine multipotent mesenchymal stromal cells promote neuroregeneration after sciatic nerve injury in rats. Stem Cell Res Ther 2021; 12:303. [PMID: 34051869 PMCID: PMC8164252 DOI: 10.1186/s13287-021-02315-8] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2020] [Accepted: 03/29/2021] [Indexed: 01/09/2023] Open
Abstract
Background Nerve injuries are debilitating, leading to long-term motor deficits. Remyelination and axonal growth are supported and enhanced by growth factor and cytokines. Combination of nerve guidance conduits (NGCs) with adipose-tissue-derived multipotent mesenchymal stromal cells (AdMSCs) has been performing promising strategy for nerve regeneration. Methods 3D-printed polycaprolactone (PCL)-NGCs were fabricated. Wistar rats subjected to critical sciatic nerve damage (12-mm gap) were divided into sham, autograft, PCL (empty NGC), and PCL + MSCs (NGC multi-functionalized with 106 canine AdMSCs embedded in heterologous fibrin biopolymer) groups. In vitro, the cells were characterized and directly stimulated with interferon-gamma to evaluate their neuroregeneration potential. In vivo, the sciatic and tibial functional indices were evaluated for 12 weeks. Gait analysis and nerve conduction velocity were analyzed after 8 and 12 weeks. Morphometric analysis was performed after 8 and 12 weeks following lesion development. Real-time PCR was performed to evaluate the neurotrophic factors BDNF, GDNF, and HGF, and the cytokine and IL-10. Immunohistochemical analysis for the p75NTR neurotrophic receptor, S100, and neurofilament was performed with the sciatic nerve. Results The inflammatory environment in vitro have increased the expression of neurotrophins BDNF, GDNF, HGF, and IL-10 in canine AdMSCs. Nerve guidance conduits multi-functionalized with canine AdMSCs embedded in HFB improved functional motor and electrophysiological recovery compared with PCL group after 12 weeks. However, the results were not significantly different than those obtained using autografts. These findings were associated with a shift in the regeneration process towards the formation of myelinated fibers. Increased immunostaining of BDNF, GDNF, and growth factor receptor p75NTR was associated with the upregulation of BDNF, GDNF, and HGF in the spinal cord of the PCL + MSCs group. A trend demonstrating higher reactivity of Schwann cells and axonal branching in the sciatic nerve was observed, and canine AdMSCs were engrafted at 30 days following repair. Conclusions 3D-printed NGCs multi-functionalized with canine AdMSCs embedded in heterologous fibrin biopolymer as cell scaffold exerted neuroregenerative effects. Our multimodal approach supports the trophic microenvironment, resulting in a pro-regenerative state after critical sciatic nerve injury in rats.
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Affiliation(s)
- Diego Noé Rodríguez-Sánchez
- Department of Veterinary Clinics, School of Veterinary Medicine and Animal Science, São Paulo State University (UNESP), Botucatu, SP, Brazil
| | - Giovana Boff Araujo Pinto
- Department of Veterinary Clinics, School of Veterinary Medicine and Animal Science, São Paulo State University (UNESP), Botucatu, SP, Brazil
| | - Luciana Politti Cartarozzi
- Department of Structural and Functional Biology, Institute of Biology, University of Campinas, Campinas, SP, Brazil
| | | | - Ana Livia Carvalho Bovolato
- Blood Transfusion Center, Cell Engineering Laboratory, Botucatu Medical School, São Paulo State University, Botucatu, SP, Brazil
| | - Marcio de Carvalho
- Department of Veterinary Clinics, School of Veterinary Medicine and Animal Science, São Paulo State University (UNESP), Botucatu, SP, Brazil
| | - Jorge Vicente Lopes da Silva
- Renato Archer Information Technology Center (CTI), Three-dimensional Technologies Research Group, Campinas, SP, Brazil
| | - Janaina de Andréa Dernowsek
- Renato Archer Information Technology Center (CTI), Three-dimensional Technologies Research Group, Campinas, SP, Brazil
| | - Marjorie Golim
- Hemocenter division of Botucatu Medical School, São Paulo State University, Botucatu, SP, Brazil
| | - Benedito Barraviera
- Center for the Study of Venoms and Venomous Animals (CEVAP), São Paulo State University (UNESP), Botucatu, SP, Brazil
| | - Rui Seabra Ferreira
- Center for the Study of Venoms and Venomous Animals (CEVAP), São Paulo State University (UNESP), Botucatu, SP, Brazil
| | - Elenice Deffune
- Blood Transfusion Center, Cell Engineering Laboratory, Botucatu Medical School, São Paulo State University, Botucatu, SP, Brazil
| | - Mathues Bertanha
- Blood Transfusion Center, Cell Engineering Laboratory, Botucatu Medical School, São Paulo State University, Botucatu, SP, Brazil
| | - Rogério Martins Amorim
- Department of Veterinary Clinics, School of Veterinary Medicine and Animal Science, São Paulo State University (UNESP), Botucatu, SP, Brazil.
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20
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Gopalakrishnan Usha P, Jalajakumari S, Sheela UB, Mohan D, Berry C, Tripathi A, Thankappan Nair ST. Engineering cartilage graft using mesenchymal stem cell laden polyacrylamide-galactoxyloglucan hydrogel for transplantation. J Biomater Appl 2021; 36:541-551. [PMID: 34018854 DOI: 10.1177/08853282211019521] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
Hydrogels are reported to have various biomedical field applications, and many reports also suggest that soft gels promote stem cell differentiation. Chondrogenic differentiation of mesenchymal stem cells (MSC) is significant in articular cartilage repair. This study focuses on polysaccharide-based hydrogels which enhance chondrocyte lineage differentiation of MSC when grown in the hydrogels. This study implies that the prepared hydrogels promote specific lineage without any external chemical induction factors. The techniques, including immunofluorescence and functional assays to assess the differentiation and in vivo implantation, were employed. All observations paved the way towards confirmation that the galactoxyloglucan-based hydrogel is an attractive candidate for supporting stem cell growth and cartilaginous differentiation.
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Affiliation(s)
- Preethi Gopalakrishnan Usha
- Laboratory of Biopharmaceuticals and Nanomedicine, Division of Cancer Research, Regional Cancer Centre, Trivandrum, India
| | - Sreekutty Jalajakumari
- Laboratory of Biopharmaceuticals and Nanomedicine, Division of Cancer Research, Regional Cancer Centre, Trivandrum, India
| | - Unnikrishnan Babukuttan Sheela
- Laboratory of Biopharmaceuticals and Nanomedicine, Division of Cancer Research, Regional Cancer Centre, Trivandrum, India
| | - Deepa Mohan
- Laboratory of Biopharmaceuticals and Nanomedicine, Division of Cancer Research, Regional Cancer Centre, Trivandrum, India
| | - Catherine Berry
- Centre for the Cellular Microenvironment, Institute of Molecular Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK
| | - Anuj Tripathi
- Nuclear Agriculture and Biotechnology Division, Bhabha Atomic Research Centre, Mumbai, India
| | - Sreelekha T Thankappan Nair
- Laboratory of Biopharmaceuticals and Nanomedicine, Division of Cancer Research, Regional Cancer Centre, Trivandrum, India
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21
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Sandonà M, Di Pietro L, Esposito F, Ventura A, Silini AR, Parolini O, Saccone V. Mesenchymal Stromal Cells and Their Secretome: New Therapeutic Perspectives for Skeletal Muscle Regeneration. Front Bioeng Biotechnol 2021; 9:652970. [PMID: 34095095 PMCID: PMC8172230 DOI: 10.3389/fbioe.2021.652970] [Citation(s) in RCA: 65] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Accepted: 04/01/2021] [Indexed: 12/14/2022] Open
Abstract
Mesenchymal stromal cells (MSCs) are multipotent cells found in different tissues: bone marrow, peripheral blood, adipose tissues, skeletal muscle, perinatal tissues, and dental pulp. MSCs are able to self-renew and to differentiate into multiple lineages, and they have been extensively used for cell therapy mostly owing to their anti-fibrotic and immunoregulatory properties that have been suggested to be at the basis for their regenerative capability. MSCs exert their effects by releasing a variety of biologically active molecules such as growth factors, chemokines, and cytokines, either as soluble proteins or enclosed in extracellular vesicles (EVs). Analyses of MSC-derived secretome and in particular studies on EVs are attracting great attention from a medical point of view due to their ability to mimic all the therapeutic effects produced by the MSCs (i.e., endogenous tissue repair and regulation of the immune system). MSC-EVs could be advantageous compared with the parental cells because of their specific cargo containing mRNAs, miRNAs, and proteins that can be biologically transferred to recipient cells. MSC-EV storage, transfer, and production are easier; and their administration is also safer than MSC therapy. The skeletal muscle is a very adaptive tissue, but its regenerative potential is altered during acute and chronic conditions. Recent works demonstrate that both MSCs and their secretome are able to help myofiber regeneration enhancing myogenesis and, interestingly, can be manipulated as a novel strategy for therapeutic interventions in muscular diseases like muscular dystrophies or atrophy. In particular, MSC-EVs represent promising candidates for cell free-based muscle regeneration. In this review, we aim to give a complete picture of the therapeutic properties and advantages of MSCs and their products (MSC-derived EVs and secreted factors) relevant for skeletal muscle regeneration in main muscular diseases.
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Affiliation(s)
- Martina Sandonà
- Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Fondazione Santa Lucia, Rome, Italy
| | - Lorena Di Pietro
- Dipartimento di Scienze della Vita e Sanità Pubblica, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Federica Esposito
- Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Fondazione Santa Lucia, Rome, Italy
| | - Alessia Ventura
- Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Fondazione Santa Lucia, Rome, Italy
| | - Antonietta Rosa Silini
- Centro di Ricerca "E. Menni", Fondazione Poliambulanza - Istituto Ospedaliero, Brescia, Italy
| | - Ornella Parolini
- Dipartimento di Scienze della Vita e Sanità Pubblica, Università Cattolica del Sacro Cuore, Rome, Italy.,Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS, Rome, Italy
| | - Valentina Saccone
- Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Fondazione Santa Lucia, Rome, Italy.,Dipartimento di Scienze della Vita e Sanità Pubblica, Università Cattolica del Sacro Cuore, Rome, Italy
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22
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Wright A, Arthaud-Day ML, Weiss ML. Therapeutic Use of Mesenchymal Stromal Cells: The Need for Inclusive Characterization Guidelines to Accommodate All Tissue Sources and Species. Front Cell Dev Biol 2021; 9:632717. [PMID: 33665190 PMCID: PMC7921162 DOI: 10.3389/fcell.2021.632717] [Citation(s) in RCA: 99] [Impact Index Per Article: 24.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Accepted: 01/07/2021] [Indexed: 12/12/2022] Open
Abstract
Following their discovery over 50 years ago, mesenchymal stromal cells (MSCs) have become one of the most studied cellular therapeutic products by both academia and industry due to their regenerative potential and immunomodulatory properties. The promise of MSCs as a therapeutic modality has been demonstrated by preclinical data yet has not translated to consistent, successful clinical trial results in humans. Despite the disparities across the field, MSC shareholders are unified under one common goal-to use MSCs as a therapeutic modality to improve the quality of life for those suffering from a malady in which the standard of care is suboptimal or no longer effective. Currently, there is no Food and Drug Administration (FDA)-approved MSC therapy on the market in the United States although several MSC products have been granted regulatory approval in other countries. In this review, we intend to identify hurdles that are impeding therapeutic progress and discuss strategies that may aid in accomplishing this universal goal of widespread therapeutic use.
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Affiliation(s)
- Adrienne Wright
- Department of Anatomy and Physiology, Kansas State University, Manhattan, KS, United States
| | - Marne L Arthaud-Day
- Department of Management, Kansas State University, Manhattan, KS, United States
| | - Mark L Weiss
- Department of Anatomy and Physiology, Kansas State University, Manhattan, KS, United States.,Midwest Institute of Comparative Stem Cell Biotechnology, Kansas State University, Manhattan, KS, United States
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23
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Voga M, Kovač V, Majdic G. Comparison of Canine and Feline Adipose-Derived Mesenchymal Stem Cells/Medicinal Signaling Cells With Regard to Cell Surface Marker Expression, Viability, Proliferation, and Differentiation Potential. Front Vet Sci 2021; 7:610240. [PMID: 33521084 PMCID: PMC7838367 DOI: 10.3389/fvets.2020.610240] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2020] [Accepted: 11/26/2020] [Indexed: 12/23/2022] Open
Abstract
Remarkable immunomodulatory abilities of mesenchymal stem cells, also called multipotent mesenchymal stromal cells or medicinal signaling cells (MSCs), have entailed significant advances in veterinary regenerative medicine in recent years. Despite positive outcomes from MSC therapies in various diseases in dogs and cats, differences in MSC characteristics between small animal veterinary patients are not well-known. We performed a comparative study of cells' surface marker expression, viability, proliferation, and differentiation capacity of adipose-derived MSCs (ADMSCs) from dogs and domestic cats. The same growth media and methods were used to isolate, characterize, and culture canine and feline ADMSCs. Adipose tissue was collected from 11 dogs and 8 cats of both sexes. The expression of surface markers CD44, CD90, and CD34 was detected by flow cytometry. Viability at passage 3 was measured with the hemocytometer and compared to the viability measured by flow cytometry after 1 day of handling. The proliferation potential of MSCs was measured by calculating cell doubling and cell doubling time from second to eighth passage. Differentiation potential was determined at early and late passages by inducing cells toward adipogenic, osteogenic, and chondrogenic differentiation using commercial media. Our study shows that the percentage of CD44+CD90+ and CD34−/− cells is higher in cells from dogs than in cells from cats. The viability of cells measured by two different methods at passage 3 differed between the species, and finally, canine ADMSCs possess greater proliferation and differentiation potential in comparison to the feline ADMSCs.
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Affiliation(s)
- Metka Voga
- Veterinary Faculty, Institute for Preclinical Sciences, University of Ljubljana, Ljubljana, Slovenia
| | - Valerija Kovač
- Blood Transfusion Centre of Slovenia, Ljubljana, Slovenia
| | - Gregor Majdic
- Veterinary Faculty, Institute for Preclinical Sciences, University of Ljubljana, Ljubljana, Slovenia.,Medical Faculty, Institute for Physiology, University of Maribor, Maribor, Slovenia
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24
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Chen S, Wang Y, Liao L, Meng L, Li J, Shi C, Han H, Zheng X, Shen H. Similar Repair Effects of Human Placenta, Bone Marrow Mesenchymal Stem Cells, and Their Exosomes for Damaged SVOG Ovarian Granulosa Cells. Stem Cells Int 2020; 2020:8861557. [PMID: 33376492 PMCID: PMC7738794 DOI: 10.1155/2020/8861557] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2020] [Revised: 11/07/2020] [Accepted: 11/18/2020] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND This study is aimed at investigating the repairing effect of mesenchymal stem cells and their exosomes from different sources on ovarian granulosa cells damaged by chemotherapy drugs-phosphoramide mustard (PM). METHODS In this study, we choose bone marrow mesenchymal stem cells (BMSCs) and human placental mesenchymal stem cells (HPMSCs) for research. Then, they were cocultured with human ovarian granulosa cells (SVOG) injured by phosphoramide mustard (PM), respectively. β-Galactosidase staining, flow cytometry, and Western blot were used to detect the changes in the senescence and apoptosis of SVOG cells before and after their coculture with the above two types of MSCs. Subsequently, exosomes from these two types of MSCs were extracted and added to the culture medium of SVOG cells after PM injury to test whether these two types of exosomes played a role similar to that of MSCs in repairing damaged SVOG cells. RESULTS PM treatment-induced apoptotic SVOG cells were significantly decreased after HPMSCs and BMSCs as compared with control group. After coculturing with these two types of MSCs, PM-treated SVOG cells showed significantly reduced senescence and apoptosis proportions as well as cleaved-Caspase 3 expression, and HPMSCs played a slightly stronger role than BMSCs in repairing SVOG cells in terms of the above three indicators. In addition, the ratios of senescent and apoptotic SVOG cells were also significantly reduced by the two types of exosomes, which played a role similar to that of MSCs in repairing cell damages. CONCLUSIONS The results indicated that BMSCs, HPMSCs, and their exosomes all exerted a certain repair effect on SVOG cells damaged by PM, and consistent repair effect was observed between exosomes and MSCs. The repair effect of exosomes secreted from BMSCs and HPMSCs on the SVOG cells was studied for the first time, and the results fully demonstrated that exosomes are the key carriers for MSCs to play their role.
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Affiliation(s)
- Shuwen Chen
- Reproductive Medical Center, Peking University People's Hospital, Peking University, Beijing 100044, China
| | - Yanbin Wang
- Reproductive Medical Center, Peking University People's Hospital, Peking University, Beijing 100044, China
| | - Liming Liao
- School of Life Sciences, Peking University, Beijing 100191, China
| | - Li Meng
- Incinta Fertility Center, Torrance, CA, USA
| | - Juanjuan Li
- Reproductive Medical Center, Peking University People's Hospital, Peking University, Beijing 100044, China
| | - Cheng Shi
- Reproductive Medical Center, Peking University People's Hospital, Peking University, Beijing 100044, China
| | - Hongjing Han
- Reproductive Medical Center, Peking University People's Hospital, Peking University, Beijing 100044, China
| | - Xiaofeng Zheng
- School of Life Sciences, Peking University, Beijing 100191, China
| | - Huan Shen
- Reproductive Medical Center, Peking University People's Hospital, Peking University, Beijing 100044, China
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25
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Ramesh T. Osteogenic differentiation potential of human bone marrow-derived mesenchymal stem cells enhanced by bacoside-A. Cell Biochem Funct 2020; 39:148-158. [PMID: 33137853 DOI: 10.1002/cbf.3596] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2020] [Revised: 09/30/2020] [Accepted: 10/07/2020] [Indexed: 01/18/2023]
Abstract
Stem cell therapy is growing rapidly to treat numerous diseases including bone-associated diseases. Mesenchymal stem cells (MSCs) are most commonly preferred to treat bone diseases because it possesses high osteogenic potency. Though, to obtain maximum osteogenic efficiency of MSCs is challenging. Therefore, this study was planned to evaluate the osteogenic efficiency of human bone marrow derived mesenchymal stem cells (hBMSCs) by bacoside-A. This study was investigated the activity of alkaline phosphatase (ALP) and expressions of the genes specific to osteogenic regulation mainly runt-related transcription factor 2 (Runx2), osterix (Osx), osteocalcin (OCN) and collagen type Iα1 (Col I α1) in hBMSCs cultured under osteogenic conditions at different concentrations of bacoside-A for 14 days. The results of this study depicted significant upregulation in the activity of ALP and expressions of osteogenic regulator genes in bacoside-A treated cells when compared with control cells. Besides, expressions of glycogen synthase kinase-3β (GSK-3β) and Wnt/β-catenin were evaluated; these expressions were also significantly increased in bacoside-A treated cells when compared with control cells. This result provides a further supporting evidence of bacoside-A role on osteogenesis in hBMSCs. The present study suggest that bacoside-A will be applied to ameliorate the process of osteogenesis in hBMSCs to repair damaged bone structure during MSC-based therapy; this will be an excellent and auspicious treatment for bone-associated disorders including osteoporosis. Significance of the study Osteoporosis is a bone metabolic disorder characterized by an imbalance between the activity of osteoblastic bone formation and osteoclastic bone resorption that disrupts the bone microarchitecture. Current anti-osteoporotic drugs are inhibiting bone resorption, but they are unable to restore the bone structure due to extreme bone remodelling process and causes numerous side effects. The finding of natural bioactive compounds with osteogenic property is very essential for osteoporosis treatment. This study was reported that bacoside-A ameliorated osteogenic differentiation of hBMSCs through upregulation of osteogenic differentiation genes and Wnt/β-catenin signalling pathway. This result is indicating that bacoside-A may be useful for osteoporosis treatments.
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Affiliation(s)
- Thiyagarajan Ramesh
- Department of Basic Medical Sciences, College of Medicine, Prince Sattam Bin Abdulaziz University, Al-Kharj, Kingdom of Saudi Arabia
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26
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Duan L, Liang Y, Xu X, Xiao Y, Wang D. Recent progress on the role of miR-140 in cartilage matrix remodelling and its implications for osteoarthritis treatment. Arthritis Res Ther 2020; 22:194. [PMID: 32811552 PMCID: PMC7437174 DOI: 10.1186/s13075-020-02290-0] [Citation(s) in RCA: 65] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2020] [Accepted: 08/07/2020] [Indexed: 01/15/2023] Open
Abstract
Cartilage matrix remodelling homeostasis is a crucial factor in maintaining cartilage integrity. Loss of cartilage integrity is a typical characteristic of osteoarthritis (OA). Strategies aimed at maintaining cartilage integrity have attracted considerable attention in the OA research field. Recently, a series of studies have suggested dual functions of microRNA-140 (miR-140) in cartilage matrix remodelling. Here, we discuss the significance of miR-140 in promoting cartilage formation and inhibiting degeneration. Additionally, we focused on the role of miR-140 in the chondrogenesis of mesenchymal stem cells (MSCs). Of note, we carefully reviewed recent advances in MSC exosomes for miRNA delivery in OA treatment.
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Affiliation(s)
- Li Duan
- Department of Orthopedics, Shenzhen Intelligent Orthopaedics and Biomedical Innovation Platform, Guangdong Artificial Intelligence Biomedical Innovation Platform, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, 518035, China
| | - Yujie Liang
- Department of Orthopedics, Shenzhen Intelligent Orthopaedics and Biomedical Innovation Platform, Guangdong Artificial Intelligence Biomedical Innovation Platform, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, 518035, China.,Department of Child and Adolescent Psychiatry, Shenzhen Kangning Hospital, Shenzhen Mental Health Center, Shenzhen, 518003, China
| | - Xiao Xu
- Department of Orthopedics, Shenzhen Intelligent Orthopaedics and Biomedical Innovation Platform, Guangdong Artificial Intelligence Biomedical Innovation Platform, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, 518035, China
| | - Yin Xiao
- Institute of Health and Biomedical Innovation, Faculty of Science and Engineering, Queensland University of Technology, Kelvin Grove Campus, Brisbane, QLD, 4059, Australia
| | - Daping Wang
- Department of Orthopedics, Shenzhen Intelligent Orthopaedics and Biomedical Innovation Platform, Guangdong Artificial Intelligence Biomedical Innovation Platform, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, 518035, China. .,Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, 518055, China.
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27
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Huňáková K, Hluchý M, Špaková T, Matejová J, Mudroňová D, Kuricová M, Rosocha J, Ledecký V. Study of bilateral elbow joint osteoarthritis treatment using conditioned medium from allogeneic adipose tissue-derived MSCs in Labrador retrievers. Res Vet Sci 2020; 132:513-520. [PMID: 32805699 DOI: 10.1016/j.rvsc.2020.08.004] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2020] [Revised: 08/03/2020] [Accepted: 08/05/2020] [Indexed: 02/08/2023]
Abstract
Canine elbow dysplasia is a common cause of forelimb lameness in dogs and can lead to development of osteoarthritis (OA). A potential alternative to pain management is the use of a safe cell-free based therapy through trophic and paracrine factors of mesenchymal stem cells (MSCs). The aim of study was to identify the profile of selected mediators of potential clinical relevance in synovial fluid (SF) samples of dogs with elbow OA and analyse the range of motion (ROM) before and after cell-free MSCs-based treatment. In this study, conditioned medium from allogeneic canine adipose tissue - derived MSC (CM-AD-MSC) was prepared and administered into both elbow joints with OA in six Labrador retriever dogs (n = 6) on day 0 and 14 without creating a control group with a placebo. The SF of the elbow joints was analysed for the presence of several biomolecules (IL-6, IL-10, IL-8, IL-2, IL-12, TNF-αIFN-γ, MMP-3TIMP-1) before and after intraarticular applications of CM-AD-MSC. Kinematic analysis was used to assess the clinical effect of CM-AD-MSC. Analyses of SF and ROM were performed on days 0, 14 and 42. Concentration levels of MMP-3, TIMP-1, IL-6 and TNF-α in SF showed significant differences before and after the treatment (P < .05). There was a significant improvement in ROM between day 0 and 42 (P < .001). No severe adverse events were observed during the study. Results support the potential supportive effect of CM-AD-MSC as a noninvasive therapeutic tool for pain management of OA elbow joints in dogs.
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Affiliation(s)
- Kristína Huňáková
- Small Animal Clinic, University of Veterinary Medicine and Pharmacy, Komenského 73, 041 81 Košice, Slovakia
| | - Marián Hluchý
- Small Animal Clinic, University of Veterinary Medicine and Pharmacy, Komenského 73, 041 81 Košice, Slovakia
| | - Tímea Špaková
- Associated Tissue Bank, Faculty of Medicine, P. J. Safarik University and L. Pasteur University Hospital, Trieda SNP 1, 040 11 Košice, Slovakia.
| | - Jana Matejová
- Associated Tissue Bank, Faculty of Medicine, P. J. Safarik University and L. Pasteur University Hospital, Trieda SNP 1, 040 11 Košice, Slovakia
| | - Dagmar Mudroňová
- Institute of Immunology, University of Veterinary Medicine and Pharmacy, Komenského 73, 041 81 Košice, Slovakia
| | - Mária Kuricová
- Small Animal Clinic, University of Veterinary Medicine and Pharmacy, Komenského 73, 041 81 Košice, Slovakia
| | - Ján Rosocha
- Associated Tissue Bank, Faculty of Medicine, P. J. Safarik University and L. Pasteur University Hospital, Trieda SNP 1, 040 11 Košice, Slovakia
| | - Valent Ledecký
- Small Animal Clinic, University of Veterinary Medicine and Pharmacy, Komenského 73, 041 81 Košice, Slovakia
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Ginsenoside Rg1 Improves Differentiation by Inhibiting Senescence of Human Bone Marrow Mesenchymal Stem Cell via GSK-3 β and β-Catenin. Stem Cells Int 2020; 2020:2365814. [PMID: 32565825 PMCID: PMC7271209 DOI: 10.1155/2020/2365814] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2020] [Revised: 04/27/2020] [Accepted: 05/08/2020] [Indexed: 12/12/2022] Open
Abstract
Objectives To demonstrate the effect of Ginsenoside Rg1 on the differentiation of human bone marrow-derived mesenchymal stem cells (hBM-MSCs). Subsequently, a rational mechanism for the detection of Rg1 which affects mesenchymal stem cell differentiation was explored. Methods Flow cytometry is used for cell identification. The differentiation ability of hBM-MSCs was studied by differentiation culture. SA-β-gal staining is used to detect cell senescence levels. Western blot and immunofluorescence were used to determine protein expression levels. RT-qPCR is used to detect mRNA expression levels. Results Rg1 regulates the differentiation of hBM-MSCs. Differentiation culture analysis showed that Rg1 promoted cells to osteogenesis and chondrogenesis. Western blot results showed that Rg1 regulated the overactivation of the β-catenin signaling pathway and significantly adjusted the phosphorylation of GSK-3β. GSK-3β inhibitor (Licl) significantly increased Rg1-induced phosphorylation of GSK-3β, which in turn reduced Rg1-induced differentiation of hBM-MSCs. Conclusion Ginsenoside Rg1 can reduce the excessive activation of the Wnt pathway in senescent cells by inhibiting the phosphorylation of GSK-3β and regulate the mesenchymal stem cell differentiation ability.
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29
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Voga M, Adamic N, Vengust M, Majdic G. Stem Cells in Veterinary Medicine-Current State and Treatment Options. Front Vet Sci 2020; 7:278. [PMID: 32656249 PMCID: PMC7326035 DOI: 10.3389/fvets.2020.00278] [Citation(s) in RCA: 73] [Impact Index Per Article: 14.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2019] [Accepted: 04/27/2020] [Indexed: 12/12/2022] Open
Abstract
Regenerative medicine is a branch of medicine that develops methods to grow, repair, or replace damaged or diseased cells, organs or tissues. It has gained significant momentum in recent years. Stem cells are undifferentiated cells with the capability to self—renew and differentiate into tissue cells with specialized functions. Stem cell therapies are therefore used to overcome the body's inability to regenerate damaged tissues and metabolic processes after acute or chronic insult. The concept of stem cell therapy was first introduced in 1991 by Caplan, who proposed that massive differentiation of cells into the desired tissue could be achieved by isolation, cultivation, and expansion of stem cells in in vitro conditions. Among different stem cell types, mesenchymal stem cells (MSC) currently seem to be the most suitable for therapeutic purposes, based on their simple isolation and culturing techniques, and lack of ethical issues regarding their usage. Because of their remarkable immunomodulatory abilities, MSCs are increasingly gaining recognition in veterinary medicine. Developments are primarily driven by the limitations of current treatment options for various medical problems in different animal species. MSCs represent a possible therapeutic option for many animal diseases, such as orthopedic, orodental and digestive tract diseases, liver, renal, cardiac, respiratory, neuromuscular, dermal, olfactory, and reproductive system diseases. Although we are progressively gaining an understanding of MSC behavior and their mechanisms of action, some of the issues considering their use for therapy are yet to be resolved. The aim of this review is first to summarize the current knowledge and stress out major issues in stem cell based therapies in veterinary medicine and, secondly, to present results of clinical usage of stem cells in veterinary patients.
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Affiliation(s)
- Metka Voga
- Faculty of Veterinary Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Neza Adamic
- Faculty of Veterinary Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Modest Vengust
- Faculty of Veterinary Medicine, University of Ljubljana, Ljubljana, Slovenia
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30
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Wright A, Snyder L, Knights K, He H, Springer NL, Lillich J, Weiss ML. A Protocol for the Isolation, Culture, and Cryopreservation of Umbilical Cord-Derived Canine Mesenchymal Stromal Cells: Role of Cell Attachment in Long-Term Maintenance. Stem Cells Dev 2020; 29:695-713. [PMID: 32148170 DOI: 10.1089/scd.2019.0145] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Mesenchymal stromal cells (MSCs) hold great promise in the field of regenerative medicine due to their ability to create a variable localized anti-inflammatory effect in injuries such as Crohn's disease and osteoarthritis or by incorporation in tissue engineered constructs. Currently, the MSC literature uses rodents for preclinical disease models. There is growing interest in using naturally occurring disease in large animals for modeling human disease. By review of the canine MSCs literature, it appears that canine MSCs can be difficult to maintain in culture for extended passages and this greatly varies between tissue sources, compared with human and rodent MSCs, and limited lifespan is an obstacle for preclinical investigation and therapeutic use. Research using canine MSCs has been focused on cells derived from bone marrow or adipose tissue, and the differences in manufacturing MSCs between laboratories are problematic due to lack of standardization. To address these issues, here, a stepwise process was used to optimize canine MSCs isolation, expansion, and cryopreservation utilizing canine umbilical cord-derived MSCs. The culture protocol utilizes coating of tissue culture surfaces that increases cellular adherence, increases colony-forming units-fibroblast efficiency, and decreases population doubling times. Canine MSCs isolated with our protocol could be maintained longer than published canine MSCs methods before senescing. Our improved cryopreservation protocols produce on average >90% viable MSCs at thaw. These methods enable master-bank and working-bank scenarios for allogeneic MSC testing in naturally occurring disease in dogs.
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Affiliation(s)
- Adrienne Wright
- Department of Anatomy and Physiology and Kansas State University College of Veterinary Medicine, Manhattan, Kansas, USA
| | - Larry Snyder
- Department of Anatomy and Physiology and Kansas State University College of Veterinary Medicine, Manhattan, Kansas, USA
| | - Kaori Knights
- Department of Diagnostic Medicine/Pathobiology, Kansas State University College of Veterinary Medicine, Manhattan, Kansas, USA
| | - Hong He
- Department of Anatomy and Physiology and Kansas State University College of Veterinary Medicine, Manhattan, Kansas, USA
| | - Nora L Springer
- Department of Diagnostic Medicine/Pathobiology, Kansas State University College of Veterinary Medicine, Manhattan, Kansas, USA
| | - James Lillich
- Department of Anatomy and Physiology and Kansas State University College of Veterinary Medicine, Manhattan, Kansas, USA
| | - Mark L Weiss
- Department of Anatomy and Physiology and Kansas State University College of Veterinary Medicine, Manhattan, Kansas, USA.,The Midwest Institute of Comparative Stem Cell Biology, Kansas State University, College of Veterinary Medicine, Manhattan, Kansas, USA
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31
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Kafarnik C, McClellan A, Dziasko M, Daniels JT, Guest DJ. Canine Corneal Stromal Cells Have Multipotent Mesenchymal Stromal Cell Properties In Vitro. Stem Cells Dev 2020; 29:425-439. [PMID: 31973649 DOI: 10.1089/scd.2019.0163] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
The objective of this study was to determine whether corneal stromal cells (CSCs) from the limbal and central corneal stroma in dogs have multipotent mesenchymal stem/stromal cell (MSC) properties, and whether this cell population can be differentiated into keratocyte-like cells (KDCs). Normal, donated, mesocephalic dog corneas were used to isolate CSC in vitro. Immunohistochemistry demonstrated a distinct population of CD90 expressing cells in the anterior stroma throughout the limbal and central cornea. CSC could be cultured from both the limbal and central cornea and the culture kinetics showed a progenitor cell profile. The CSC expressed stem cell markers CD90, CD73, CD105, N-cadherin, and Pax6, while CD34 was negative. Limbal and central CSC differentiated into osteoblasts, chondrocytes, and adipocytes confirming their multipotency. Coculturing allogeneic peripheral blood mononuclear cells (PBMCs) with limbal CSCs did not affect baseline PBMC proliferation indicating a degree of innate immune privilege. Limbal CSC could be differentiated into KDCs that expressed Keratocan, Lumican, and ALDH1A3 and downregulated Pax6 and N-cadherin. In conclusion, canine CSCs have multipotent MSC properties similarly described in humans and could serve as a source of cells for cell therapy and studying corneal diseases.
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Affiliation(s)
- Christiane Kafarnik
- Centre for Preventive Medicine, Animal Health Trust, Newmarket, United Kingdom.,Rescue, Repair and Regeneration Theme, Institute of Ophthalmology, University College London, London, United Kingdom
| | - Alyce McClellan
- Centre for Preventive Medicine, Animal Health Trust, Newmarket, United Kingdom
| | - Marc Dziasko
- Rescue, Repair and Regeneration Theme, Institute of Ophthalmology, University College London, London, United Kingdom
| | - Julie T Daniels
- Rescue, Repair and Regeneration Theme, Institute of Ophthalmology, University College London, London, United Kingdom
| | - Deborah J Guest
- Centre for Preventive Medicine, Animal Health Trust, Newmarket, United Kingdom
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32
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Shahid MA, Kim WH, Kweon OK. Cryopreservation of heat-shocked canine adipose-derived mesenchymal stromal cells with 10% dimethyl sulfoxide and 40% serum results in better viability, proliferation, anti-oxidation, and in-vitro differentiation. Cryobiology 2019; 92:92-102. [PMID: 31785238 DOI: 10.1016/j.cryobiol.2019.11.040] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2019] [Revised: 11/17/2019] [Accepted: 11/22/2019] [Indexed: 12/17/2022]
Abstract
Cryopreserved canine adipose-derived mesenchymal stromal cells (Ad-MSCs) can be used instantly in dogs for clinical uses. However, cryopreservation results in a reduction of the cellular viability, proliferation, and anti-oxidation of post-thawed Ad-MSCs. Therefore, there is a need for in-vitro procedure to improve post-thawed Ad-MSCs' viability, proliferation, anti-oxidation, and differentiation capacity. In this study, fresh-Ad-MSCs were activated with heat shock, hypoxia (5% O2), or hypoxia (5% O2) + heat shock treatments. The results showed that compared to the other treatments, heat shock significantly improved the proliferation rate, anti-oxidation, heat shock proteins and growth factors expressions of canine-fresh-Ad-MSCs. Consequently, fresh-Ad-MSCs were heat-shocked and then cryopreserved with different combinations of dimethyl sulfoxide (Me2SO) and fetal bovine serum (FBS) to determine the combination that could effectively preserve the cellular viability, proliferation, anti-oxidation and differentiation capacity of Ad-MSCs after cryopreservation. We found that C-HST-Ad-MSCs cryopreserved with 10% Me2SO + 40% FBS presented significantly (p < 0.05) improved cellular viability, proliferation rate, anti-oxidant capacity, and differentiation potential as compared to C-HST-Ad-MSCs cryopreserved with 1% Me2SO + 10% FBS or 1% Me2SO alone or control. We concluded, heat shock treatment is much better to enhance the characteristics of fresh-Ad-MSCs than other treatments, moreover, C-HST-Ad-MSCs in 10% Me2SO + 40% FBS showed better results compared to other cryopreserved groups. However, future work is required to optimize the expression of heat shock proteins, which would further improve the characteristics of fresh- and cryopreserved-HST-Ad-MSCs and reduce the dependency on Me2SO and FBS.
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Affiliation(s)
- Muhammad Afan Shahid
- Research Institute for Veterinary Science and College of Veterinary Medicine Building 85, Room 623, Seoul National University, Gwanak-gu, Gwanak-ro 1, Seoul, 08826, South Korea.
| | - Wan Hee Kim
- Research Institute for Veterinary Science and College of Veterinary Medicine Building 85, Room 623, Seoul National University, Gwanak-gu, Gwanak-ro 1, Seoul, 08826, South Korea.
| | - Oh-Kyeong Kweon
- Research Institute for Veterinary Science and College of Veterinary Medicine Building 85, Room 623, Seoul National University, Gwanak-gu, Gwanak-ro 1, Seoul, 08826, South Korea.
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Mesenchymal stem cell-based bone tissue engineering for veterinary practice. Heliyon 2019; 5:e02808. [PMID: 31844733 PMCID: PMC6895744 DOI: 10.1016/j.heliyon.2019.e02808] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2019] [Revised: 10/29/2019] [Accepted: 11/07/2019] [Indexed: 01/17/2023] Open
Abstract
Bone tissue engineering has been widely studied and proposed as a promising platform for correcting the bone defects. The applications of mesenchymal stem cell (MSC)-based bone tissue engineering have been investigated in various in vitro and in vivo models. In this regard, the promising animal bone defect models have been employed for illustrating the bone regenerative capacity of MSC-based bone tissue engineering. However, most studies aimed for clinical applications in human. These evidences suggest a knowledge gap to fulfill the accomplishment for veterinary implementation. In this review, the fundamental concept, knowledge, and technology of MSC-based bone tissue engineering focusing on veterinary applications are summarized. In addition, the potential canine MSCs resources for veterinary bone tissue engineering are reviewed, including canine bone marrow-derived MSCs, canine adipose-derived MSCs, and canine dental tissue-derived MSCs. This review will provide a basic and current information for studies aiming for the utilization of MSC-based bone tissue engineering in veterinary practice.
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Dental mesenchymal stem cells and neuro-regeneration: a focus on spinal cord injury. Cell Tissue Res 2019; 379:421-428. [PMID: 31776822 DOI: 10.1007/s00441-019-03109-4] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2018] [Accepted: 09/22/2019] [Indexed: 02/07/2023]
Abstract
Regenerative medicine is a branch of translational research that aims to reestablish irreparably damaged tissues and organs by stimulating the body's own repair mechanisms via the implantation of stem cells differentiated into specialized cell types. A rich source of adult stem cells is located inside the tooth and is represented by human dental pulp stem cells, or hDPSCs. These cells are characterized by a high proliferative rate, have self-renewal and multi-lineage differentiation properties and are often used for tissue engineering and regenerative medicine. The present review will provide an overview of hDPSCs and related features with a special focus on their potential applications in regenerative medicine of the nervous system, such as, for example, after spinal cord injury. Recent advances in the identification and characterization of dental stem cells and in dental tissue engineering strategies suggest that bioengineering approaches may successfully be used to regenerate districts of the central nervous system, previously considered irreparable.
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Madhusoodan AP, Das K, Mili B, Kumar K, Kumar A, Saxena AC, Singh P, Dutt T, Bag S. In vitro proliferation and differentiation of canine bone marrow derived mesenchymal stem cells over hydroxyl functionalized CNT substrates. ACTA ACUST UNITED AC 2019; 24:e00387. [PMID: 31799142 PMCID: PMC6881647 DOI: 10.1016/j.btre.2019.e00387] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2019] [Revised: 09/06/2019] [Accepted: 10/14/2019] [Indexed: 11/26/2022]
Abstract
Nanotopography of culture substrate acts as a positive cue in cell-biomaterial based tissue regeneration. Considering the potentiality of carbon nanotubes (CNTs) this study was designed to evaluate its two functionalized form by an in vitro culture condition using canine mesenchymal stem cells as cellular model. Cells were isolated and its behaviour, proliferation and differentiation processes were elucidated onto CNT substrates. Beside the variations in cellular behaviour it was remarkably noted that even though proliferation was reduced but osteogenic and chondrogenic differentiation was enhanced over multi-walled CNTs, whereas neuronal differentiation was better supported by single walled CNTs as evidenced by our cytochemical, immunocytochemical, gene expression and flow cytometry assays. The former one was noticed more cytocompatible by our different apoptosis studies. The outcome of these experiments collectively indicated that hydroxylated functionalized CNTs could be a potential scaffold constituent for future experimentations as well as for the application in regenerative medicine.
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Affiliation(s)
- A P Madhusoodan
- Division of Physiology and Climatology, ICAR - Indian Veterinary Research Institute, Izatnagar, Uttar Pradesh, India
| | - Kinsuk Das
- Division of Physiology and Climatology, ICAR - Indian Veterinary Research Institute, Izatnagar, Uttar Pradesh, India
| | - Bhabesh Mili
- Division of Physiology and Climatology, ICAR - Indian Veterinary Research Institute, Izatnagar, Uttar Pradesh, India
| | - Kuldeep Kumar
- Division of Physiology and Climatology, ICAR - Indian Veterinary Research Institute, Izatnagar, Uttar Pradesh, India
| | - Ajay Kumar
- Biochemistry and Food Science Section, ICAR - Indian Veterinary Research Institute, Izatnagar, Uttar Pradesh, India
| | - A C Saxena
- Division of Surgery, Izatnagar, ICAR - Indian Veterinary Research Institute, Uttar Pradesh, India
| | - Praveen Singh
- Biophysics, Electron Microscopy and Instrumentation Section, ICAR - Indian Veterinary Research Institute, Izatnagar, Uttar Pradesh, India
| | - Triveni Dutt
- Division of Livestock Production and Management, ICAR - Indian Veterinary Research Institute, Izatnagar, Uttar Pradesh, India
| | - Sadhan Bag
- Division of Physiology and Climatology, ICAR - Indian Veterinary Research Institute, Izatnagar, Uttar Pradesh, India
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Qi Y, Ma J, Li S, Liu W. Applicability of adipose-derived mesenchymal stem cells in treatment of patients with type 2 diabetes. Stem Cell Res Ther 2019; 10:274. [PMID: 31455405 PMCID: PMC6712852 DOI: 10.1186/s13287-019-1362-2] [Citation(s) in RCA: 67] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Type 2 diabetes mellitus (T2DM) is mainly characterized by insulin resistance (IR) and impaired insulin secretion. The chronic inflammatory process contributed to IR and could also hamper pancreatic β cell function. However, currently applied treatment cannot reverse β cell damage or alleviate inflammation. Mesenchymal stem cells (MSCs), the cell-based therapy for their self-renewable, differentiation potential, and immunosuppressive properties, have been demonstrated in displaying therapeutic effects in T2DM. Adipose-derived MSCs (AD-MSCs) attracted more attention due to less harvested inconvenience and ethical issues commonly accompany with bone marrow-derived MSCs (BM-MSCs) and fetal annex-derived MSCs. Both AD-MSC therapy studies and mechanism explorations in T2DM animals presented that AD-MSCs could translate to clinical application. However, hyperglycemia, hyperinsulinemia, and metabolic disturbance in T2DM are crucial for impairment of AD-MSC function, which may limit the therapeutical effects of MSCs. This review focuses on the outcomes and the molecular mechanisms of MSC therapies in T2DM which light up the hope of AD-MSCs as an innovative strategy to cure T2DM.
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Affiliation(s)
- Yicheng Qi
- Division of Endocrinology and Metabolism, Department of Internal Medicine, RenJi Hospital, School of Medicine, Shanghai Jiaotong University, 160# Pujian Road, Pudong, Shanghai, 200127, China
| | - Jing Ma
- Division of Endocrinology and Metabolism, Department of Internal Medicine, RenJi Hospital, School of Medicine, Shanghai Jiaotong University, 160# Pujian Road, Pudong, Shanghai, 200127, China
| | - Shengxian Li
- Division of Endocrinology and Metabolism, Department of Internal Medicine, RenJi Hospital, School of Medicine, Shanghai Jiaotong University, 160# Pujian Road, Pudong, Shanghai, 200127, China
| | - Wei Liu
- Division of Endocrinology and Metabolism, Department of Internal Medicine, RenJi Hospital, School of Medicine, Shanghai Jiaotong University, 160# Pujian Road, Pudong, Shanghai, 200127, China.
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Saadeldin IM, Swelum AAA, Noreldin AE, Tukur HA, Abdelazim AM, Abomughaid MM, Alowaimer AN. Isolation and Culture of Skin-Derived Differentiated and Stem-Like Cells Obtained from the Arabian Camel ( Camelus dromedarius). Animals (Basel) 2019; 9:ani9060378. [PMID: 31226810 PMCID: PMC6616910 DOI: 10.3390/ani9060378] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2019] [Revised: 06/10/2019] [Accepted: 06/15/2019] [Indexed: 12/22/2022] Open
Abstract
Simple Summary This is the first comprehensive study to isolate different cellular types and stem-like cells from the camel skin. We reported the multipotency of the isolated stem cells. Moreover, some unique cells were observed, such as dermal cyst-forming cells. This discovery represents a cheap and easy source for camel stem cells that is essential for development of the elite camel regenerative medicine and provides a good source of camel fibroblast required for camel cloning. Abstract Elite camels often suffer from massive injuries. Thus, there is a pivotal need for a cheap and readily available regenerative medicine source. We isolated novel stem-like cells from camel skin and investigated their multipotency and resistance against various stresses. Skin samples were isolated from ears of five camels. Fibroblasts, keratinocytes, and spheroid progenitors were extracted. After separation of different cell lines by trypsinization, all cell lines were exposed to heat shock. Then, fibroblasts and dermal cyst-forming cells were examined under cryopreservation. Dermal cyst-forming cells were evaluated for resistance against osmotic pressure. The results revealed that resistance periods against trypsin were 1.5, 4, and 7 min for fibroblasts, keratinocytes, and spheroid progenitors, respectively. Furthermore, complete recovery of different cell lines after heat shock along with the differentiation of spheroid progenitors into neurons was observed. Fibroblasts and spheroid progenitors retained cell proliferation after cryopreservation. Dermal cyst-forming cells regained their normal structure after collapsing by osmotic pressure. The spheroid progenitors incubated in the adipogenic, osteogenic, and neurogenic media differentiated into adipocyte-, osteoblast-, and neuron-like cells, respectively. To the best of our knowledge, we isolated different unique cellular types and stem-like cells from the camel skin and examined their multipotency for the first time.
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Affiliation(s)
- Islam M Saadeldin
- Department of Animal Production, College of Food and Agricultural Sciences, King Saud University, Riyadh 11451, Saudi Arabia.
- Department of Physiology, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44519, Egypt.
| | - Ayman Abdel-Aziz Swelum
- Department of Animal Production, College of Food and Agricultural Sciences, King Saud University, Riyadh 11451, Saudi Arabia.
- Department of Theriogenology, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44519, Egypt.
| | - Ahmed E Noreldin
- Histology and Cytology Department, Faculty of Veterinary Medicine, Damanhour University, Damanhour 22511, Egypt.
| | - Hammed A Tukur
- Department of Animal Production, College of Food and Agricultural Sciences, King Saud University, Riyadh 11451, Saudi Arabia.
| | - Aaser M Abdelazim
- Department of Basic Medical Sciences, College of Applied Medical Sciences, University of Bisha, Bisha 61922, Saudi Arabia.
- Department of Biochemistry, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44519, Egypt.
| | - Mosleh M Abomughaid
- Department of Medical Laboratory Sciences, College of Applied Medical Sciences, University of Bisha, Bisha 61922, Saudi Arabia.
| | - Abdullah N Alowaimer
- Department of Animal Production, College of Food and Agricultural Sciences, King Saud University, Riyadh 11451, Saudi Arabia.
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Endo K, Fujita N, Nakagawa T, Nishimura R. Comparison of the effect of growth factors on chondrogenesis of canine mesenchymal stem cells. J Vet Med Sci 2019; 81:1211-1218. [PMID: 31167981 PMCID: PMC6715918 DOI: 10.1292/jvms.18-0551] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Mesenchymal stem cells (MSCs) are proposed to be useful in cartilage regenerative
medicine, however, canine MSCs have been reported to show poor chondrogenic capacity.
Therefore, optimal conditions for chondrogenic differentiation should be determined by
mimicking the developmental process. We have previously established novel and superior
canine MSCs named bone marrow peri-adipocyte cells (BM-PACs) and the objective of this
study was to evaluate the effects of growth factors required for in vivo
chondrogenesis using canine BM-PACs. Spheroids of BM-PACs were cultured in chondrogenic
medium containing 10 ng/ml transforming growth factor-β1
(TGF-β1) with or without 100 ng/ml bone morphogenetic
protein-2 (BMP-2), 100 ng/ml growth differentiation
factor-5 (GDF-5) or 100 ng/ml insulin-like growth
factor-1 (IGF-1). Chondrogenic differentiation was evaluated by the quantification of
glycosaminoglycan and Safranin O staining for proteoglycan production. The expression of
cartilage matrix or hypertrophic gene/protein was also evaluated by qPCR and
immunohistochemistry. Spheroids in all groups were strongly stained with Safranin O.
Although BMP-2 significantly increased glycosaminoglycan production, Safranin O-negative
outer layer was formed and the mRNA expression of COL10 relating to cartilage hypertrophy
was also significantly upregulated (P<0.05). GDF-5 promoted the
production of glycosaminoglycan and type II collagen without increasing COL10 mRNA
expression. The supplementation of IGF-1 did not significantly affect cartilaginous and
hypertrophic differentiation. Our results indicate that GDF-5 is a useful growth factor
for the generation of articular cartilage from canine MSCs.
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Affiliation(s)
- Kentaro Endo
- Laboratory of Veterinary Surgery, Graduate School of Agriculture and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan
| | - Naoki Fujita
- Laboratory of Veterinary Surgery, Graduate School of Agriculture and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan
| | - Takayuki Nakagawa
- Laboratory of Veterinary Surgery, Graduate School of Agriculture and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan
| | - Ryohei Nishimura
- Laboratory of Veterinary Surgery, Graduate School of Agriculture and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan
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Endo K, Fujita N, Nakagawa T, Nishimura R. Effect of Fibroblast Growth Factor-2 and Serum on Canine Mesenchymal Stem Cell Chondrogenesis. Tissue Eng Part A 2019; 25:901-910. [PMID: 30319056 DOI: 10.1089/ten.tea.2018.0177] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
IMPACT STATEMENT Tissue engineering using the chondrogenic potential of mesenchymal stem cells (MSCs) is a promising approach for cartilage regenerative therapy. Although dogs are widely used as an animal model for cartilage regeneration, chondrogenic differentiation of canine MSCs is still challenging. In this study, we aimed at establishing the optimal conditions for canine MSC chondrogenesis. Our results demonstrated that preconditioning with fibroblast growth factor-2 and serum-free induction medium enabled robust chondrogenesis of canine MSCs. These findings will allow effective generation of cartilage tissue from canine MSCs and advance research of cartilage regeneration in both dogs and humans.
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Affiliation(s)
- Kentaro Endo
- Laboratory of Veterinary Surgery, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Tokyo, Japan
| | - Naoki Fujita
- Laboratory of Veterinary Surgery, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Tokyo, Japan
| | - Takayuki Nakagawa
- Laboratory of Veterinary Surgery, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Tokyo, Japan
| | - Ryohei Nishimura
- Laboratory of Veterinary Surgery, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Tokyo, Japan
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40
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Sasaki A, Mizuno M, Mochizuki M, Sekiya I. Mesenchymal stem cells for cartilage regeneration in dogs. World J Stem Cells 2019; 11:254-269. [PMID: 31171954 PMCID: PMC6545524 DOI: 10.4252/wjsc.v11.i5.254] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2019] [Revised: 03/29/2019] [Accepted: 04/09/2019] [Indexed: 02/06/2023] Open
Abstract
Articular cartilage damage and osteoarthritis (OA) are common orthopedic diseases in both humans and dogs. Once damaged, the articular cartilage seldom undergoes spontaneous repair because of its avascular, aneural, and alymphatic state, and the damage progresses to a chronic and painful situation. Dogs have distinctive characteristics compared to other laboratory animal species in that they share an OA pathology with humans. Dogs can also require treatment for naturally developed OA; therefore, effective treatment methods for OA are desired in veterinary medicine as well as in human medicine. Recently, interest has grown in regenerative medicine that includes the use of mesenchymal stem cells (MSCs). In cartilage repair, MSCs are a promising therapeutic tool due to their self-renewal capacity, ability to differentiate into cartilage, potential for trophic factor production, and capacity for immunomodulation. The MSCs from dogs (canine MSCs; cMSCs) share various characteristics with MSCs from other animal species, but they show some deviations, particularly in their differentiation ability and surface epitope expression. In vivo studies of cMSCs have demonstrated that intraarticular cMSC injection into cartilage lesions results in excellent hyaline cartilage regeneration. In clinical situations, cMSCs have shown great therapeutic effects, including amelioration of pain and lameness in dogs suffering from OA. However, some issues remain, such as a lack of regulations or guidelines and a need for unified methods for the use of cMSCs. This review summarizes what is known about cMSCs, including their in vitro characteristics, their therapeutic effects in cartilage lesion treatment in preclinical in vivo studies, their clinical efficacy for treatment of naturally developed OA in dogs, and the current limitations of cMSC studies.
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Affiliation(s)
- Akari Sasaki
- Laboratory of Veterinary Emergency Medicine, Graduate School of Agricultural and Life Sciences, the University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan
| | - Mitsuru Mizuno
- Center for Stem Cell and Regenerative Medicine, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8519, Japan
| | - Manabu Mochizuki
- Laboratory of Veterinary Emergency Medicine, Graduate School of Agricultural and Life Sciences, the University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan
| | - Ichiro Sekiya
- Center for Stem Cell and Regenerative Medicine, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8519, Japan
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Fathi E, Farahzadi R, Sheikhzadeh N. Immunophenotypic characterization, multi-lineage differentiation and aging of zebrafish heart and liver tissue-derived mesenchymal stem cells as a novel approach in stem cell-based therapy. Tissue Cell 2019; 57:15-21. [PMID: 30947959 DOI: 10.1016/j.tice.2019.01.006] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2018] [Revised: 01/24/2019] [Accepted: 01/26/2019] [Indexed: 02/07/2023]
Abstract
Mesenchymal stem cells (MSCs) are a good model for preclinical and clinical investigations, and alternative sources of MSCs are subject to intensive experiments. In this study, mesenchymal stem cells (MSCs) were isolated from heart and liver tissue of Zebrafish (Danio rerio). The flow-cytometry as well as RT-PCR were used to analyze the expression of a panel of cell surface markers CD44, CD90, CD31 and CD34. In the following, alizarin red, oil red-O and toluidine blue staining were carried out to evaluate the multi-lineage differentiation of zebrafish heart and liver tissue-derived MSCs. Subsequently, the gene and protein expression of Oct4, Sox2 and Nanog as pluri-potent markers were analyzed by RT-PCR and western blotting, respectively. In addition, MTT assay was used for cell proliferation potential and population doubling time (PDT) assessment. Also, the aging of cells was investigated by β-galactosidase activity assay. The results showed that, like other MSCs, zebrafish heart and liver tissue-derived MSCs were positive for mesenchymal, negative for hematopoietic markers and expressed pluripotent markers Oct4, Sox2 and Nanog. Moreover, these cells were differentiated to osteocyte, adipocyte, and chondrocyte lineages following directed differentiation. It was found that PDT of zebrafish heart and liver tissue-derived MSCs were 50.67 and 46.61 h, respectively. These cells had significantly more rapid growth on day 4. Our results show that zebrafish heart and liver tissue-derived MSCs exhibited typical MSC characteristics including fibroblast morphology, multi-lineage differentiation capacity, pluripotency potential and expression of a typical set of classic MSC surface markers.
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Affiliation(s)
- Ezzatollah Fathi
- Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran.
| | - Raheleh Farahzadi
- Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Najmeh Sheikhzadeh
- Department of Food Hygiene and Aquatic Animals, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran
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Barboni B, Russo V, Berardinelli P, Mauro A, Valbonetti L, Sanyal H, Canciello A, Greco L, Muttini A, Gatta V, Stuppia L, Mattioli M. Placental Stem Cells from Domestic Animals: Translational Potential and Clinical Relevance. Cell Transplant 2019; 27:93-116. [PMID: 29562773 PMCID: PMC6434480 DOI: 10.1177/0963689717724797] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
The field of regenerative medicine is moving toward clinical practice in veterinary science. In this context, placenta-derived stem cells isolated from domestic animals have covered a dual role, acting both as therapies for patients and as a valuable cell source for translational models. The biological properties of placenta-derived cells, comparable among mammals, make them attractive candidates for therapeutic approaches. In particular, stemness features, low immunogenicity, immunomodulatory activity, multilineage plasticity, and their successful capacity for long-term engraftment in different host tissues after autotransplantation, allo-transplantation, or xenotransplantation have been demonstrated. Their beneficial regenerative effects in domestic animals have been proven using preclinical studies as well as clinical trials starting to define the mechanisms involved. This is, in particular, for amniotic-derived cells that have been thoroughly studied to date. The regenerative role arises from a mutual tissue-specific cell differentiation and from the paracrine secretion of bioactive molecules that ultimately drive crucial repair processes in host tissues (e.g., anti-inflammatory, antifibrotic, angiogenic, and neurogenic factors). The knowledge acquired so far on the mechanisms of placenta-derived stem cells in animal models represent the proof of concept of their successful use in some therapeutic treatments such as for musculoskeletal disorders. In the next future, legislation in veterinary regenerative medicine will be a key element in order to certify those placenta-derived cell-based protocols that have already demonstrated their safety and efficacy using rigorous approaches and to improve the degree of standardization of cell-based treatments among veterinary clinicians.
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Affiliation(s)
- B Barboni
- 1 Faculty of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo, Teramo, Italy
| | - V Russo
- 1 Faculty of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo, Teramo, Italy
| | - P Berardinelli
- 1 Faculty of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo, Teramo, Italy
| | - A Mauro
- 1 Faculty of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo, Teramo, Italy
| | - L Valbonetti
- 1 Faculty of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo, Teramo, Italy
| | - H Sanyal
- 1 Faculty of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo, Teramo, Italy
| | - A Canciello
- 1 Faculty of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo, Teramo, Italy
| | - L Greco
- 1 Faculty of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo, Teramo, Italy
| | - A Muttini
- 1 Faculty of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo, Teramo, Italy
| | - V Gatta
- 1 Faculty of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo, Teramo, Italy
| | - L Stuppia
- 2 Medical Genetics, University "G. d'Annunzio" of Chieti Pescara, Chieti, Italy
| | - M Mattioli
- 3 Istituto Zooprofilattico Sperimentale dell'Abruzzo e del Molise "G. Caporale," Teramo, Italy
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Gugjoo MB, Amarpal A, Sharma GT. Mesenchymal stem cell basic research and applications in dog medicine. J Cell Physiol 2019; 234:16779-16811. [PMID: 30790282 DOI: 10.1002/jcp.28348] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2018] [Revised: 01/25/2019] [Accepted: 01/28/2019] [Indexed: 12/13/2022]
Abstract
The stem cells, owing to their special characteristics like self-renewal, multiplication, homing, immunomodulation, anti-inflammatory, and dedifferentiation are considered to carry an "all-in-one-solution" for diverse clinical problems. However, the limited understanding of cellular physiology currently limits their definitive therapeutic use. Among various stem cell types, currently mesenchymal stem cells are extensively studied for dog clinical applications owing to their readily available sources, easy harvesting, and ability to differentiate both into mesodermal, as well as extramesodermal tissues. The isolated, culture expanded, and characterized cells have been applied both at preclinical as well as clinical settings in dogs with variable but mostly positive results. The results, though positive, are currently inconclusive and demands further intensive research on the properties and their dependence on the applications. Further, numerous clinical conditions of dog resemble to that of human counterparts and thus, if proved rewarding in the former may act as basis of therapy for the latter. The current review throws some light on dog mesenchymal stem cell properties and their potential therapeutic applications.
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Affiliation(s)
- Mudasir Bashir Gugjoo
- Division of Veterinary Clinical Complex, Faculty of Veterinary Sciences and Animal Husbandry, SKUAST-K, Jammu and Kashmir, India
| | - Amarpal Amarpal
- Division of Surgery, Indian Veterinary Research Institute, Izatnagar, India
| | - Gutulla Taru Sharma
- Division of Physiology and Climatology, Indian Veterinary Research Institute, Izatnagar, India
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Human amnion-derived mesenchymal stem cell (hAD-MSC) transplantation improves ovarian function in rats with premature ovarian insufficiency (POI) at least partly through a paracrine mechanism. Stem Cell Res Ther 2019; 10:46. [PMID: 30683144 PMCID: PMC6347748 DOI: 10.1186/s13287-019-1136-x] [Citation(s) in RCA: 145] [Impact Index Per Article: 24.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2018] [Revised: 01/03/2019] [Accepted: 01/06/2019] [Indexed: 12/21/2022] Open
Abstract
Background Chemotherapy can induce premature ovarian insufficiency (POI) and reduce fertility in young female patients. Currently, there is no effective therapy for POI. Human amnion-derived mesenchymal stem cells (hAD-MSCs) may be a promising seed cell for regenerative medicine. This study investigated the effects and mechanisms of hAD-MSC transplantation on chemotherapy-induced POI in rats. Methods Chemotherapy-induced POI rat models were established by intraperitoneal injection of cyclophosphamide. Seventy-two female SD rats were randomly divided into control, POI, and hAD-MSC-treated groups. hAD-MSCs were labeled with PKH26 and injected into the tail veins of POI rats. To examine the underlying mechanisms, the differentiation of transplanted hAD-MSCs in the POI ovaries was analyzed by immunofluorescent staining. The in vitro expression of growth factors secreted by hAD-MSCs in hAD-MSC-conditioned media (hAD-MSC-CM) was analyzed by ELISA. Sixty female SD rats were divided into control, POI, and hAD-MSC-CM-treated groups, and hAD-MSC-CM was injected into the bilateral ovaries of POI rats. After hAD-MSC transplantation or hAD-MSC-CM injection, serum sex hormone levels, estrous cycles, ovarian pathological changes, follicle counts, granulosa cell (GC) apoptosis, and Bcl-2, Bax, and VEGF expression in ovaries were examined. Results PKH26-labeled hAD-MSCs mainly homed to ovaries after transplantation. hAD-MSC transplantation reduced ovarian injury and improved ovarian function in rats with POI. Transplanted hAD-MSCs were only located in the interstitium of ovaries, rather than in follicles, and did not express the typical markers of oocytes and GCs, which are ZP3 and FSHR, respectively. hAD-MSCs secreted FGF2, IGF-1, HGF, and VEGF, and those growth factors were detected in the hAD-MSC-CM. hAD-MSC-CM injection improved the local microenvironment of POI ovaries, leading to a decrease in Bax expression and an increase in Bcl-2 and endogenous VEGF expression in ovarian cells, which inhibited chemotherapy-induced GC apoptosis, promoted angiogenesis and regulated follicular development, thus partly reducing ovarian injury and improving ovarian function in rats with POI. Conclusions hAD-MSC transplantation can improve ovarian function in rats with chemotherapy-induced POI at least partly through a paracrine mechanism. The presence of a paracrine mechanism accounting for hAD-MSC-mediated recovery of ovarian function might be attributed to the growth factors secreted by hAD-MSCs.
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Ayala-Cuellar AP, Kang JH, Jeung EB, Choi KC. Roles of Mesenchymal Stem Cells in Tissue Regeneration and Immunomodulation. Biomol Ther (Seoul) 2019; 27:25-33. [PMID: 29902862 PMCID: PMC6319543 DOI: 10.4062/biomolther.2017.260] [Citation(s) in RCA: 103] [Impact Index Per Article: 17.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2017] [Revised: 03/27/2018] [Accepted: 04/16/2018] [Indexed: 12/14/2022] Open
Abstract
Mesenchymal stem cells are classified as multipotent stem cells, due to their capability to transdifferentiate into various lineages that develop from mesoderm. Their popular appeal as cell-based therapy was initially based on the idea of their ability to restore tissue because of their differentiation potential in vitro; however, the lack of evidence of their differentiation to target cells in vivo led researchers to focus on their secreted trophic factors and their role as potential powerhouses on regulation of factors under different immunological environments and recover homeostasis. To date there are more than 800 clinical trials on humans related to MSCs as therapy, not to mention that in animals is actively being applied as therapeutic resource, though it has not been officially approved as one. But just as how results from clinical trials are important, so is to reveal the biological mechanisms involved on how these cells exert their healing properties to further enhance the application of MSCs on potential patients. In this review, we describe characteristics of MSCs, evaluate their benefits as tissue regenerative therapy and combination therapy, as well as their immunological properties, activation of MSCs that dictate their secreted factors, interactions with other immune cells, such as T cells and possible mechanisms and pathways involved in these interactions.
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Affiliation(s)
| | - Ji-Houn Kang
- Laboratory of Internal Medicine, Republic of Korea
| | - Eui-Bae Jeung
- Laboratory of Biochemistry and Molecular Biology, Veterinary Medical Center and College of Veterinary Medicine, Chungbuk National University, Republic of Korea
| | - Kyung-Chul Choi
- Laboratory of Biochemistry and Immunology, Republic of Korea.,Institute of Life Science and Bio-Engineering, TheraCell Bio & Science, Cheongju 28644, Republic of Korea
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Abstract
Stem cell therapy has tremendous potential for clinical application in the treatment of a variety of diseases in veterinary medicine. Based on the known desirable immunomodulatory properties of mesenchymal stem cells, this therapy has potential for treatment of a variety of renal diseases. This review details our current understanding of stem cell biology and proposed mechanism of action as applicable to renal disease. Studies performed in chronic kidney disease clinical trials and models of acute kidney injury are summarized with the goal of providing an overview of the current status of this treatment modality and its potential for the future.
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Affiliation(s)
- Jessica M Quimby
- Department of Veterinary Clinical Sciences, The Ohio State University, 601 Vernon Tharp Road, Columbus, OH 43210, USA.
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Comparative analysis and characterization of soluble factors and exosomes from cultured adipose tissue and bone marrow mesenchymal stem cells in canine species. Vet Immunol Immunopathol 2018; 208:6-15. [PMID: 30712794 DOI: 10.1016/j.vetimm.2018.12.003] [Citation(s) in RCA: 69] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2018] [Revised: 12/13/2018] [Accepted: 12/17/2018] [Indexed: 01/08/2023]
Abstract
The two main sources of mesenchymal stem cell (MSCs) in the canine species are bone marrow (cBM-MSCs) and adipose tissue (cAd-MSCs). The secretion of multitude bioactive molecules, included under the concept of secretome and found in the cultured medium, play a predominant role in the mechanism of action of these cells on tissue regeneration. Although certain features of its characterization are well documented, their secretory profiles remain unknown. We described and compared, for the first time, the secretory profile and exosomes characterization in standard monolayer culture of MSCs from both sources of the same donor as well as its immunomodulatory potential. We found that despite the similarity in surface immunophenotyping and trilineage differentiation, there are several differences in terms of proliferation rate and secretory profile. cAd-MSCs have advantages in proliferative capacity, whereas cBM-MSCs showed a significantly higher secretory production of some soluble factors (IL-10, IL-2, IL-6, IL-8, IL-12p40, IFN-γ, VEGF-A, NGF-β, TGF-β, NO and PGE2) and exosomes under the same standard culture conditions. Proteomics analysis confirm that cBM-MSCs exosomes have a greater number of characterized proteins involved in metabolic processes and in the regulation of biological processes compared to cAd-MSCs. On the other hand, secretome from both sources demonstrate similar immunomodulatory capacity when tested in mitogen stimulated lymphocyte reaction, but not in their exosomes at the dose used. Considering that the use of secretome open as a new therapeutic strategy for different diseases, without the need to implant cells, those biological differences should be considered, when choosing the MSCs source, for either cellular implantation or direct use of secretome for a specific clinical application.
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Steffen F, Bertolo A, Affentranger R, Ferguson SJ, Stoyanov J. Treatment of Naturally Degenerated Canine Lumbosacral Intervertebral Discs with Autologous Mesenchymal Stromal Cells and Collagen Microcarriers: A Prospective Clinical Study. Cell Transplant 2018; 28:201-211. [PMID: 30488736 PMCID: PMC6362527 DOI: 10.1177/0963689718815459] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Intervertebral disc (IVD) degeneration is a frequent disease in modern societies and at its later stages is likely to cause chronic low back pain. Although many studies have been published, the available treatments for IVD degeneration fail to promote regeneration or even marginal repair of the IVD structure. In this study, we aimed to establish veterinary canine patients as a translational large animal model that recapitulates IVD degeneration that occurs in humans, and to investigate the suitability of intradiscal application of mesenchymal stromal cells (MSC). Twenty client-owned dogs diagnosed with spontaneous degenerative lumbosacral IVD and low back pain were included in the study. Autologous MSC were isolated from bone marrow and cultured for 2 weeks. Prior to injection, MSC were attached on collagen microcarriers for delivery, with or without TGF-β1 crosslinking. After decompressive spinal surgery, dogs received an intradiscal injection of MSC-microcarriers (n = 11), MSC-TGF-β1-microcarriers (n = 6) or microcarriers only (control, n = 3). MSC-microcarriers were initially evaluated in vitro and ex vivo, to test cell chondrogenic potential and biomechanical properties of the microcarriers, respectively. Clinical performance and Pfirrmann grading were evaluated at 10 months after the injection by magnetic resonance imaging. MSC differentiated successfully in vitro towards chondrogenic phenotype and biomechanical tests showed no significant differences of IVD stiffness after microcarrier injection. In vivo injection was successful in all dogs, without any visible leakage, and clinical functioning was restored back to normality. However, postoperative Pfirrmann grade remained identical in all dogs, and formation of Schmorl’s nodes was detected in 45% of dogs. This side effect was reduced by halving the injection volume, which was then observed only in 11% of dogs. In conclusion, we observed marked clinical improvement in all groups, despite the formation of Schmorl’s nodes, but microcarriers and MSC failed to regenerate the structure of degenerated IVD.
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Affiliation(s)
- Frank Steffen
- 1 Vetsuisse faculty of the University of Zurich, Zurich, Switzerland
| | | | | | | | - Jivko Stoyanov
- 2 Swiss Paraplegic Research, Nottwil, Switzerland.,4 Institute for Surgical Technology and Biomechanics, University of Bern, Bern, Switzerland
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Zomer HD, Roballo KC, Lessa TB, Bressan FF, Gonçalves NN, Meirelles FV, Trentin AG, Ambrósio CE. Distinct features of rabbit and human adipose-derived mesenchymal stem cells: implications for biotechnology and translational research. STEM CELLS AND CLONING-ADVANCES AND APPLICATIONS 2018; 11:43-54. [PMID: 30425533 PMCID: PMC6204872 DOI: 10.2147/sccaa.s175749] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Introduction Owing to their similarity with humans, rabbits are useful for multiple applications in biotechnology and translational research from basic to preclinical studies. In this sense, mesenchymal stem cells (MSCs) are known for their therapeutic potential and promising future in regenerative medicine. As many studies have been using rabbit adipose-derived MSCs (ASCs) as a model of human ASCs (hASCs), it is fundamental to compare their characteristics and understand how distinct features could affect the translation to human medicine. Objective The aim of this study was to comparatively characterize rabbit ASCs (rASCs) and hASCs to further uses in biotechnology and translational studies. Materials and methods rASCs and hASCs were isolated and characterized by their immunophenotype, differentiation potential, proliferative profile, and nuclear stability in vitro. Results and discussion Both ASCs presented differentiation potential to osteocytes, chondrocytes, and adipocytes and shared similar immunophenotype expression to CD105+, CD34−, and CD45−, but rabbit cells expressed significantly lower CD73 and CD90 than human cells. In addition, rASCs presented greater clonogenic potential and proliferation rate than hASCs but no difference in nuclear alterations. Conclusion The distinct features of rASCs and hASCs can positively or negatively affect their use for different applications in biotechnology (such as cell reprogramming) and translational studies (such as cell transplantation, tissue engineering, and pharmacokinetics). Nevertheless, the particularities between rabbit and human MSCs should not prevent rabbit use in preclinical models, but care should be taken to interpret results and properly translate animal findings to medicine.
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Affiliation(s)
- Helena Debiazi Zomer
- Department of Cell Biology, Embryology and Genetic, Faculty of Biological Sciences, Santa Catarina Federal University (UFSC), Florianópolis, Brazil.,Department of Surgery, Sector Anatomy, Faculty of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, Brazil,
| | - Kelly Cs Roballo
- Department of Surgery, Sector Anatomy, Faculty of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, Brazil,
| | - Thais Borges Lessa
- Department of Surgery, Sector Anatomy, Faculty of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, Brazil,
| | - Fabiana Fernandes Bressan
- Department of Surgery, Sector Anatomy, Faculty of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, Brazil,
| | - Natália Nardeli Gonçalves
- Department of Surgery, Sector Anatomy, Faculty of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, Brazil,
| | - Flávio Vieira Meirelles
- Department of Surgery, Sector Anatomy, Faculty of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, Brazil, .,Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, University of São Paulo, São Paulo, Brazil,
| | - Andrea Gonçalves Trentin
- Department of Cell Biology, Embryology and Genetic, Faculty of Biological Sciences, Santa Catarina Federal University (UFSC), Florianópolis, Brazil
| | - Carlos Eduardo Ambrósio
- Department of Surgery, Sector Anatomy, Faculty of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, Brazil, .,Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, University of São Paulo, São Paulo, Brazil,
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Sasaki A, Mizuno M, Ozeki N, Katano H, Otabe K, Tsuji K, Koga H, Mochizuki M, Sekiya I. Canine mesenchymal stem cells from synovium have a higher chondrogenic potential than those from infrapatellar fat pad, adipose tissue, and bone marrow. PLoS One 2018; 13:e0202922. [PMID: 30138399 PMCID: PMC6107231 DOI: 10.1371/journal.pone.0202922] [Citation(s) in RCA: 60] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2018] [Accepted: 08/10/2018] [Indexed: 01/17/2023] Open
Abstract
Osteoarthritis (OA), a common chronic joint disorder in both humans and canines, is characterized by a progressive loss of articular cartilage. Canines can serve as an animal model of OA for human medicine, and this research can simultaneously establish effective veterinary treatments for canine OA. One attractive treatment that can lead to cartilage regeneration is the use of mesenchymal stem cells (MSCs). However, for canine OA, little information is available regarding the best source of MSCs. The purpose of this study was to identify a promising MSC source for canine cartilage regeneration. We collected synovial, infrapatellar fat pad, inguinal adipose, and bone marrow tissues from six canines and then conducted a donor-matched comparison of the properties of MSCs derived from these four tissues. We examined the surface epitope expression, proliferation capacity, and trilineage differentiation potential of all four populations. Adherent cells derived from all four tissue sources exhibited positivity for CD90 and CD44 and negativity for CD45 and CD11b. The positive rate for CD90 was higher for synovium-derived than for adipose-derived and bone marrow-derived MSCs. Synovium-derived and infrapatellar fat pad-derived MSCs displayed substantial proliferation ability, and all four populations underwent trilineage differentiation. During chondrogenesis, the wet weight was heavier for cartilage pellets derived from synovium MSCs than from the other three sources. The synovium is therefore a promising source for MSCs for canine cartilage regeneration. Our findings provide useful information about canine MSCs that may be applicable to regenerative medicine for treatment of OA.
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Affiliation(s)
- Akari Sasaki
- Center for Stem Cell and Regenerative Medicine, Tokyo Medical and Dental University, Tokyo, Japan
- Department of Veterinary Medical Sciences, the University of Tokyo, Tokyo, Japan
| | - Mitsuru Mizuno
- Center for Stem Cell and Regenerative Medicine, Tokyo Medical and Dental University, Tokyo, Japan
| | - Nobutake Ozeki
- Center for Stem Cell and Regenerative Medicine, Tokyo Medical and Dental University, Tokyo, Japan
| | - Hisako Katano
- Center for Stem Cell and Regenerative Medicine, Tokyo Medical and Dental University, Tokyo, Japan
| | - Koji Otabe
- Center for Stem Cell and Regenerative Medicine, Tokyo Medical and Dental University, Tokyo, Japan
| | - Kunikazu Tsuji
- Department of Cartilage Regeneration, Tokyo Medical and Dental University, Tokyo, Japan
| | - Hideyuki Koga
- Department of Joint Surgery and Sports Medicine, Tokyo Medical and Dental University, Tokyo, Japan
| | - Manabu Mochizuki
- Department of Veterinary Medical Sciences, the University of Tokyo, Tokyo, Japan
| | - Ichiro Sekiya
- Center for Stem Cell and Regenerative Medicine, Tokyo Medical and Dental University, Tokyo, Japan
- * E-mail:
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