1
|
Wang S, Gao D, Li M, Wang Q, Du X, Yuan S. Enhanced Wound Healing and Autogenesis Through Lentiviral Transfection of Adipose-Derived Stem Cells Combined with Dermal Substitute. Biomedicines 2024; 12:2844. [PMID: 39767750 PMCID: PMC11673073 DOI: 10.3390/biomedicines12122844] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2024] [Revised: 12/08/2024] [Accepted: 12/12/2024] [Indexed: 01/11/2025] Open
Abstract
BACKGROUND Burns and chronic ulcers may cause severe skin loss, leading to critical health issues like shock, infection, sepsis, and multiple organ failure. Effective healing of full-thickness wounds may be challenging, with traditional methods facing limitations due to tissue shortage, infection, and lack of structural support. METHODS This study explored the combined use of gene transfection and dermal substitutes to improve wound healing. We used the DGTM (genes: DNP63A, GRHL2, TFAP2A, and MYC) factors to transfect adipose-derived stem cells (ADSCs), inducing their differentiation into keratinocytes. These transfected ADSCs were then incorporated into Pelnac® dermal substitutes to enhance vascularization and cellular proliferation for better healing outcomes. RESULTS Gene transfer using DGTM factors successfully induced keratinocyte differentiation in ADSCs. The application of these differentiated cells with Pelnac® dermal substitute to dermal wounds in mice resulted in the formation of skin tissue with a normal epidermal layer and proper collagen organization. This method alleviates the tediousness of the multiple transfection steps in previous protocols and the safety issues caused by using viral transfection reagents directly on the wound. Additionally, the inclusion of dermal substitutes addressed the lack of collagen and elastic fibers, promoting the formation of tissue resembling healthy skin rather than scar tissue. CONCLUSION Integrating DGTM factor-transfected ADSCs with dermal substitutes represents a novel strategy for enhancing the healing of full-thickness wounds. Further research and clinical trials are warranted to optimize and validate this innovative approach for broader clinical applications.
Collapse
Affiliation(s)
- Shiqi Wang
- Department of Plastic Surgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210002, China; (S.W.); (D.G.); (M.L.)
- Department of Plastic Surgery, Jinling Hospital, Nanjing School of Clinical Medicine, Southern Medical University, Nanjing 210002, China;
| | - Dinghui Gao
- Department of Plastic Surgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210002, China; (S.W.); (D.G.); (M.L.)
| | - Mingyu Li
- Department of Plastic Surgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210002, China; (S.W.); (D.G.); (M.L.)
| | - Qian Wang
- Department of Plastic Surgery, Jinling Hospital, Nanjing School of Clinical Medicine, Southern Medical University, Nanjing 210002, China;
| | - Xuanyu Du
- Department of Plastic Surgery, Jinling Hospital, School of Medicine, Southeast University, Nanjing 210002, China;
| | - Siming Yuan
- Department of Plastic Surgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210002, China; (S.W.); (D.G.); (M.L.)
- Department of Plastic Surgery, Jinling Hospital, Nanjing School of Clinical Medicine, Southern Medical University, Nanjing 210002, China;
| |
Collapse
|
2
|
Lo C, Cao L, Lin Y, Wang H. The Effect of Botulinum Toxin Type A in the Autologous Fat Grafting: A Review. J Cosmet Dermatol 2024; 23:3828-3835. [PMID: 39305094 PMCID: PMC11626320 DOI: 10.1111/jocd.16550] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2024] [Revised: 08/01/2024] [Accepted: 08/13/2024] [Indexed: 12/10/2024]
Abstract
BACKGROUND Autologous fat grafting is a widely used technique in plastic and reconstructive surgery for soft tissue augmentation. Despite its advantages, the primary limitation is the unpredictable retention rate of transplanted fat. Recent studies suggest that botulinum toxin type A (BTX-A) can enhance fat graft survival by promoting angiogenesis and muscle paralysis. AIMS This review explores the potential of BTX-A as an adjuvant in autologous fat grafting, providing insights into its mechanisms, benefits, and the need for further clinical validation. PATIENTS/METHODS A literature review was conducted using PubMed, Web of Science, MEDLINE, and Embase. Keywords related to BTX-A, fat grafting, fat graft survival, and angiogenesis were used. Comparative studies reporting histological changes following BTX-A application in fat grafting were included. Exclusion criteria involved case reports with fewer than three animals, reviews, and letters. RESULTS The initial search yielded 108 articles, with seven experimental studies meeting the criteria. These studies demonstrated that BTX-A enhances fat graft retention by promoting vascularization and adipose-derived stem cell differentiation. However, these results are mainly based on small animal models. CONCLUSIONS While BTX-A shows promise in improving autologous fat grafting outcomes, its efficacy and safety in humans need validation through large-scale clinical trials. Translating these preclinical findings into human trials is crucial to establish standardized protocols and optimize clinical outcomes. Future research should focus on optimizing dosage and injection sites, conducting long-term follow-up studies, and performing multicenter trials to verify the findings.
Collapse
Affiliation(s)
- Chihchieh Lo
- Department of Oral and Maxillofacial Surgery and State Key Laboratory of Oral DiseasesSichuan University West China College of StomatologyChengduSichuanChina
| | - Lideng Cao
- Department of Oral and Maxillofacial Surgery and State Key Laboratory of Oral DiseasesSichuan University West China College of StomatologyChengduSichuanChina
| | - Yuanyou Lin
- Department of Oral and Maxillofacial Surgery and State Key Laboratory of Oral DiseasesSichuan University West China College of StomatologyChengduSichuanChina
| | - Hang Wang
- Department of Oral and Maxillofacial Surgery and State Key Laboratory of Oral DiseasesSichuan University West China College of StomatologyChengduSichuanChina
| |
Collapse
|
3
|
Freitas-Ribeiro S, Moreira H, da Silva LP, Noro J, Sampaio-Marques B, Ludovico P, Jarnalo M, Horta R, Marques AP, Reis RL, Pirraco RP. Prevascularized spongy-like hydrogels maintain their angiogenic potential after prolonged hypothermic storage. Bioact Mater 2024; 37:253-268. [PMID: 38585489 PMCID: PMC10997873 DOI: 10.1016/j.bioactmat.2024.02.035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2023] [Revised: 02/07/2024] [Accepted: 02/29/2024] [Indexed: 04/09/2024] Open
Abstract
The chronic shortage of organs and tissues for transplantation represents a dramatic burden on healthcare systems worldwide. Tissue engineering offers a potential solution to address these shortages, but several challenges remain, with prevascularization being a critical factor for in vivo survival and integration of tissue engineering products. Concurrently, a different challenge hindering the clinical implementation of such products, regards their efficient preservation from the fabrication site to the bedside. Hypothermia has emerged as a potential solution for this issue due to its milder effects on biologic systems in comparison with other cold preservation methodologies. Its impact on prevascularization, however, has not been well studied. In this work, 3D prevascularized constructs were fabricated using adipose-derived stromal vascular fraction cells and preserved at 4 °C using Hypothermosol or basal culture media (α-MEM). Hypothermosol efficiently preserved the structural and cellular integrity of prevascular networks as compared to constructs before preservation. In contrast, the use of α-MEM led to a clear reduction in prevascular structures, with concurrent induction of high levels of apoptosis and autophagy at the cellular level. In vivo evaluation using a chorioallantoic membrane model demonstrated that, in opposition to α-MEM, Hypothermosol preservation retained the angiogenic potential of constructs before preservation by recruiting a similar number of blood vessels from the host and presenting similar integration with host tissue. These results emphasize the need of studying the impact of preservation techniques on key properties of tissue engineering constructs such as prevascularization, in order to validate and streamline their clinical application.
Collapse
Affiliation(s)
- Sara Freitas-Ribeiro
- 3B's Research Group, I3Bs – Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017, Barco, Guimarães, Portugal
- ICVS/3B's–PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - Helena Moreira
- 3B's Research Group, I3Bs – Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017, Barco, Guimarães, Portugal
- ICVS/3B's–PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - Lucília P. da Silva
- 3B's Research Group, I3Bs – Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017, Barco, Guimarães, Portugal
- ICVS/3B's–PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - Jennifer Noro
- 3B's Research Group, I3Bs – Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017, Barco, Guimarães, Portugal
- ICVS/3B's–PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - Belém Sampaio-Marques
- ICVS/3B's–PT Government Associate Laboratory, Braga/Guimarães, Portugal
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal
| | - Paula Ludovico
- ICVS/3B's–PT Government Associate Laboratory, Braga/Guimarães, Portugal
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal
| | - Mariana Jarnalo
- Department of Plastic and Reconstructive Surgery, and Burn Unity, Centro Hospitalar de São João, Porto, Portugal
- Faculty of Medicine - University of Porto, Portugal
| | - Ricardo Horta
- Department of Plastic and Reconstructive Surgery, and Burn Unity, Centro Hospitalar de São João, Porto, Portugal
- Faculty of Medicine - University of Porto, Portugal
| | - Alexandra P. Marques
- 3B's Research Group, I3Bs – Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017, Barco, Guimarães, Portugal
- ICVS/3B's–PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - Rui L. Reis
- 3B's Research Group, I3Bs – Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017, Barco, Guimarães, Portugal
- ICVS/3B's–PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - Rogério P. Pirraco
- 3B's Research Group, I3Bs – Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017, Barco, Guimarães, Portugal
- ICVS/3B's–PT Government Associate Laboratory, Braga/Guimarães, Portugal
| |
Collapse
|
4
|
van Rhijn-Brouwer FCCC, Wever KE, Kiffen R, van Rhijn JR, Gremmels H, Fledderus JO, Vernooij RWM, Verhaar MC. Systematic review and meta-analysis of the effect of bone marrow-derived cell therapies on hind limb perfusion. Dis Model Mech 2024; 17:dmm050632. [PMID: 38616715 PMCID: PMC11139036 DOI: 10.1242/dmm.050632] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2023] [Accepted: 04/03/2024] [Indexed: 04/16/2024] Open
Abstract
Preclinical and clinical studies on the administration of bone marrow-derived cells to restore perfusion show conflicting results. We conducted a systematic review and meta-analysis on preclinical studies to assess the efficacy of bone marrow-derived cells in the hind limb ischemia model and identify possible determinants of therapeutic efficacy. In vivo animal studies were identified using a systematic search in PubMed and EMBASE on 10 January 2022. 85 studies were included for systematic review and meta-analysis. Study characteristics and outcome data on relative perfusion were extracted. The pooled mean difference was estimated using a random effects model. Risk of bias was assessed for all included studies. We found a significant increase in perfusion in the affected limb after administration of bone marrow-derived cells compared to that in the control groups. However, there was a high heterogeneity between studies, which could not be explained. There was a high degree of incomplete reporting across studies. We therefore conclude that the current quality of preclinical research is insufficient (low certainty level as per GRADE assessment) to identify specific factors that might improve human clinical trials.
Collapse
Affiliation(s)
| | - Kimberley Elaine Wever
- Department of Anaesthesiology, Pain and Palliative Medicine, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
| | - Romy Kiffen
- Department of Anaesthesiology, Pain and Palliative Medicine, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
| | - Jon-Ruben van Rhijn
- Institute of Life Sciences and Chemistry, HU University of Applied Sciences Utrecht, 3584 CS Utrecht, The Netherlands
| | - Hendrik Gremmels
- Department of Medical Microbiology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands
| | - Joost Ougust Fledderus
- Department of Nephrology and Hypertension, Regenerative Medicine Center Utrecht, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands
| | - Robin Wilhelmus Maria Vernooij
- Department of Nephrology and Hypertension, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, The Netherlands
| | - Marianne Christina Verhaar
- Department of Nephrology and Hypertension, Regenerative Medicine Center Utrecht, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands
| |
Collapse
|
5
|
Bour F, Khalilollah S, Omraninava M, Mirzaie MS, Taghiloo S, Mehrparvar S, Nasiry D, Raoofi A. Three-dimensional bioengineered dermal derived matrix scaffold in combination with adipose-derived stem cells accelerate diabetic wound healing. Tissue Cell 2024; 87:102302. [PMID: 38219451 DOI: 10.1016/j.tice.2024.102302] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Revised: 12/18/2023] [Accepted: 01/02/2024] [Indexed: 01/16/2024]
Abstract
Due to the multifactorial nature of diabetic wounds, the most effective treatments require combinatorial approach. Herein we investigated whether engraftment of a bioengineered three-dimensional dermal derived matrix scaffold (DDMS) in combination with adipose-derived stem cells (ADSs), could accelerate diabetic wound healing. Diabetic animals were randomly planned into the control group, DDMS group, ADS group, and DDMS+ADS group. On days 7, 14, and 21, tissue samples were obtained for stereological, molecular, and tensiometrical assessments. We found that the wound contraction rate, the total volumes of new epidermis and dermis, the numerical densities of fibroblasts and blood vessels, collagen density, and tensiometrical parameters were meaningfully greater in the treated groups than in the control group, and these changes were more obvious in the DDMS+ADS ones (p < 0.05). Moreover, the expression of TGF-β, bFGF, and VEGF genes were considerably upregulated in treated groups compared to the control group and were greater in the DDMS+ADS group (p < 0.05). This is while expression of TNF-α and IL-1β, as well as the numerical densities of neutrophils and macrophages decreased more considerably in the DDMS+ADS group than in the other groups (p < 0.05). Overall, it was found that using both DDMS engraftment and ADS transplantation has more impact on diabetic wound healing.
Collapse
Affiliation(s)
- Fatemeh Bour
- Babol University of Medical Sciences, Babol, Iran
| | - Shayan Khalilollah
- School of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Melody Omraninava
- Health Reproductive Research Center, Islamic Azad University, Sari, Iran
| | | | - Saeid Taghiloo
- School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
| | - Sophia Mehrparvar
- Student Research Committee, Sabzevar University of Medical Sciences, Sabzevar, Iran
| | - Davood Nasiry
- Department of Paramedicine, Amol School of Paramedical Sciences, Mazandaran University of Medical Sciences, Sari, Iran.
| | - Amir Raoofi
- Cellular and Molecular Research Center, Sabzevar University of Medical Sciences, Sabzevar, Iran.
| |
Collapse
|
6
|
Alheib O, da Silva LP, Mesquita KA, da Silva Morais A, Pirraco RP, Reis RL, Correlo VM. Human adipose-derived mesenchymal stem cells laden in gellan gum spongy-like hydrogels for volumetric muscle loss treatment. Biomed Mater 2023; 18:065005. [PMID: 37604159 DOI: 10.1088/1748-605x/acf25b] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2023] [Accepted: 08/21/2023] [Indexed: 08/23/2023]
Abstract
BACKGROUND volumetric muscle loss (VML) is a traumatic massive loss of muscular tissue which frequently leads to amputation, limb loss, or lifetime disability. The current medical intervention is limited to autologous tissue transfer, which usually leads to non-functional tissue recovery. Tissue engineering holds a huge promise for functional recovery. METHODS in this work, we evaluated the potential of human adipose-derived mesenchymal stem cells (hASCs) pre-cultured in gellan gum based spongy-like hydrogels (SLHs). RESULTS in vitro, hASCs were spreading, proliferating, and releasing growth factors and cytokines (i.e. fibroblast growth factor, hepatocyte growth factor, insulin-like growth factor 1, interleukin-6 (IL-6), IL-8, IL-10, vascular endothelial growth factor) important for muscular regeneration. After implantation into a volumetric muscle loss (VML) mouse model, implants were degrading overtime, entirely integrating into the host between 4 and 8 weeks. In both SLH and SLH + hASCs defects, infiltrated cells were observed inside constructs associated with matrix deposition. Also, minimal collagen deposition was marginally observed around the constructs along both time-points. Neovascularization (CD31+vessels) and neoinnervation (β-III tubulin+bundles) were significantly detected in the SLH + hASCs group, in relation to the SHAM (empty lesion). A higher density ofα-SA+and MYH7+cells were found in the injury site among all different experimental groups, at both time-points, in relation to the SHAM. The levels ofα-SA, MyoD1, and myosin heavy chain proteins were moderately increased in the SLH + hASCs group after 4 weeks, and in the hASCs group after 8 weeks, in relation to the SHAM. CONCLUSIONS taken together, defects treated with hASCs-laden SLH promoted angiogenesis, neoinnervation, and the expression of myogenic proteins.
Collapse
Affiliation(s)
- Omar Alheib
- 3B's Research Group, I3Bs-Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017 Barco, Guimarães, Portugal
- ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - Lucilia P da Silva
- 3B's Research Group, I3Bs-Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017 Barco, Guimarães, Portugal
- ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - Katia A Mesquita
- 3B's Research Group, I3Bs-Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017 Barco, Guimarães, Portugal
- ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - Alain da Silva Morais
- 3B's Research Group, I3Bs-Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017 Barco, Guimarães, Portugal
- ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - Rogério P Pirraco
- 3B's Research Group, I3Bs-Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017 Barco, Guimarães, Portugal
- ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - Rui L Reis
- 3B's Research Group, I3Bs-Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017 Barco, Guimarães, Portugal
- ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - Vitor M Correlo
- 3B's Research Group, I3Bs-Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017 Barco, Guimarães, Portugal
- ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal
| |
Collapse
|
7
|
Markina YV, Kirichenko TV, Tolstik TV, Bogatyreva AI, Zotova US, Cherednichenko VR, Postnov AY, Markin AM. Target and Cell Therapy for Atherosclerosis and CVD. Int J Mol Sci 2023; 24:10308. [PMID: 37373454 DOI: 10.3390/ijms241210308] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2023] [Revised: 06/06/2023] [Accepted: 06/16/2023] [Indexed: 06/29/2023] Open
Abstract
Cardiovascular diseases (CVD) and, in particular, atherosclerosis, remain the main cause of death in the world today. Unfortunately, in most cases, CVD therapy begins after the onset of clinical symptoms and is aimed at eliminating them. In this regard, early pathogenetic therapy for CVD remains an urgent problem in modern science and healthcare. Cell therapy, aimed at eliminating tissue damage underlying the pathogenesis of some pathologies, including CVD, by replacing it with various cells, is of the greatest interest. Currently, cell therapy is the most actively developed and potentially the most effective treatment strategy for CVD associated with atherosclerosis. However, this type of therapy has some limitations. In this review, we have tried to summarize the main targets of cell therapy for CVD and atherosclerosis in particular based on the analysis using the PubMed and Scopus databases up to May 2023.
Collapse
Affiliation(s)
- Yuliya V Markina
- Petrovsky National Research Center of Surgery, Moscow 119991, Russia
| | | | - Taisiya V Tolstik
- Petrovsky National Research Center of Surgery, Moscow 119991, Russia
| | | | - Ulyana S Zotova
- Petrovsky National Research Center of Surgery, Moscow 119991, Russia
| | | | - Anton Yu Postnov
- Petrovsky National Research Center of Surgery, Moscow 119991, Russia
| | - Alexander M Markin
- Petrovsky National Research Center of Surgery, Moscow 119991, Russia
- Peoples' Friendship University of Russia named after Patrice Lumumba (RUDN University), Moscow 117198, Russia
| |
Collapse
|
8
|
Freitas-Ribeiro S, Diogo GS, Oliveira C, Martins A, Silva TH, Jarnalo M, Horta R, Reis RL, Pirraco RP. Growth Factor-Free Vascularization of Marine-Origin Collagen Sponges Using Cryopreserved Stromal Vascular Fractions from Human Adipose Tissue. Mar Drugs 2022; 20:md20100623. [PMID: 36286447 PMCID: PMC9604698 DOI: 10.3390/md20100623] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Revised: 09/19/2022] [Accepted: 09/28/2022] [Indexed: 11/05/2022] Open
Abstract
The successful integration of transplanted three-dimensional tissue engineering (TE) constructs depends greatly on their rapid vascularization. Therefore, it is essential to address this vascularization issue in the initial design of constructs for perfused tissues. Two of the most important variables in this regard are scaffold composition and cell sourcing. Collagens with marine origins overcome some issues associated with mammal-derived collagen while maintaining their advantages in terms of biocompatibility. Concurrently, the freshly isolated stromal vascular fraction (SVF) of adipose tissue has been proposed as an advantageous cell fraction for vascularization purposes due to its highly angiogenic properties, allowing extrinsic angiogenic growth factor-free vascularization strategies for TE applications. In this study, we aimed at understanding whether marine collagen 3D matrices could support cryopreserved human SVF in maintaining intrinsic angiogenic properties observed for fresh SVF. For this, cryopreserved human SVF was seeded on blue shark collagen sponges and cultured up to 7 days in a basal medium. The secretome profile of several angiogenesis-related factors was studied throughout culture times and correlated with the expression pattern of CD31 and CD146, which showed the formation of a prevascular network. Upon in ovo implantation, increased vessel recruitment was observed in prevascularized sponges when compared with sponges without SVF cells. Immunohistochemistry for CD31 demonstrated the improved integration of prevascularized sponges within chick chorioalantoic membrane (CAM) tissues, while in situ hybridization showed human cells lining blood vessels. These results demonstrate the potential of using cryopreserved SVF combined with marine collagen as a streamlined approach to improve the vascularization of TE constructs.
Collapse
Affiliation(s)
- Sara Freitas-Ribeiro
- 3B’s Research Group, I3Bs—Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Barco, 4805-017 Guimarães, Portugal
- ICVS/3B’s—PT Government Associate Laboratory, Braga, 4710-057 Guimarães, Portugal
| | - Gabriela S. Diogo
- 3B’s Research Group, I3Bs—Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Barco, 4805-017 Guimarães, Portugal
- ICVS/3B’s—PT Government Associate Laboratory, Braga, 4710-057 Guimarães, Portugal
| | - Catarina Oliveira
- 3B’s Research Group, I3Bs—Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Barco, 4805-017 Guimarães, Portugal
- ICVS/3B’s—PT Government Associate Laboratory, Braga, 4710-057 Guimarães, Portugal
| | - Albino Martins
- 3B’s Research Group, I3Bs—Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Barco, 4805-017 Guimarães, Portugal
- ICVS/3B’s—PT Government Associate Laboratory, Braga, 4710-057 Guimarães, Portugal
| | - Tiago H. Silva
- 3B’s Research Group, I3Bs—Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Barco, 4805-017 Guimarães, Portugal
- ICVS/3B’s—PT Government Associate Laboratory, Braga, 4710-057 Guimarães, Portugal
| | - Mariana Jarnalo
- Department of Plastic and Reconstructive Surgery, and Burn Unity, Centro Hospitalar de São João, 4200-319 Porto, Portugal
- Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal
| | - Ricardo Horta
- Department of Plastic and Reconstructive Surgery, and Burn Unity, Centro Hospitalar de São João, 4200-319 Porto, Portugal
- Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal
| | - Rui L. Reis
- 3B’s Research Group, I3Bs—Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Barco, 4805-017 Guimarães, Portugal
- ICVS/3B’s—PT Government Associate Laboratory, Braga, 4710-057 Guimarães, Portugal
| | - Rogério P. Pirraco
- 3B’s Research Group, I3Bs—Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Barco, 4805-017 Guimarães, Portugal
- ICVS/3B’s—PT Government Associate Laboratory, Braga, 4710-057 Guimarães, Portugal
- Correspondence:
| |
Collapse
|
9
|
Integrin-specific hydrogels for growth factor-free vasculogenesis. NPJ Regen Med 2022; 7:57. [PMID: 36167724 PMCID: PMC9515164 DOI: 10.1038/s41536-022-00253-4] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Accepted: 09/12/2022] [Indexed: 11/30/2022] Open
Abstract
Integrin-binding biomaterials have been extensively evaluated for their capacity to enable de novo formation of capillary-like structures/vessels, ultimately supporting neovascularization in vivo. Yet, the role of integrins as vascular initiators in engineered materials is still not well understood. Here, we show that αvβ3 integrin-specific 3D matrices were able to retain PECAM1+ cells from the stromal vascular fraction (SVF) of adipose tissue, triggering vasculogenesis in vitro in the absence of extrinsic growth factors. Our results suggest that αvβ3-RGD-driven signaling in the formation of capillary-like structures prevents the activation of the caspase 8 pathway and activates the FAK/paxillin pathway, both responsible for endothelial cells (ECs) survival and migration. We also show that prevascularized αvβ3 integrin-specific constructs inosculate with the host vascular system fostering in vivo neovascularization. Overall, this work demonstrates the ability of the biomaterial to trigger vasculogenesis in an integrin-specific manner, by activating essential pathways for EC survival and migration within a self-regulatory growth factor microenvironment. This strategy represents an improvement to current vascularization routes for Tissue Engineering constructs, potentially enhancing their clinical applicability.
Collapse
|
10
|
The Effect of Mesenchymal Stem Cells, Adipose Tissue Derived Stem Cells, and Cellular Stromal Vascular Fraction on the Repair of Acute Anal Sphincter Injury in Rats. Bioengineering (Basel) 2022; 9:bioengineering9070318. [PMID: 35877369 PMCID: PMC9311655 DOI: 10.3390/bioengineering9070318] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Revised: 06/20/2022] [Accepted: 06/21/2022] [Indexed: 11/17/2022] Open
Abstract
Background: Anal sphincter incontinence (ASI) can cause a serious decline in the quality of life and can cause a socioeconomic burden. Studies have shown that bone marrow mesenchymal stem cells (MSC) have significant therapeutic effects on ASI, but the cost and risk of MSC harvest limit their further application. In contrast, adipose tissue derived stem cells (ADSC) and cellular stromal vascular fraction (CSVF) as stem cell sources have multipotency and the advantage of easy harvest. Objective: Here we aim to investigate the effects of ADSC and CSVF on treating ASI and compare them to that of bone marrow MSC. Methods: Bone marrow MSC, ADSC, and CSVF were obtained and labeled with green fluorescent protein (GFP), and CSVF was labeled with DIL. Sprague Dawley (SD) rats were divided into 5 groups. Four groups were injected with 0.2 mL phosphate buffer saline (PBS), 1 × 107/0.2 mL of MSC, ADSC, or CSVF, respectively, after model establishment. The control group received no treatment. The repair was assessed by anal functional tests and immunostaining on day 5 and day 10 after injection. Results: MSC, ADSC, and CSVF significantly promoted tissue repair and the recovery of muscle contraction and electromyographic activity in ASI. The generation of myosatellite cells by injected MSC, ADSC, and CSVF was found in the wounded area. On day 5, CSVF showed highest therapeutic effect, while on day 10, MSC and ADSC showed higher therapeutic effects than CSVF. When comparing the effects of MSC and ADSC, ADSC was slightly better than MSC in the indexes of anal pressure, etc. Conclusion: ADSC and CVSF are alternative stem cell sources for ASI repair.
Collapse
|
11
|
Effectiveness of preconditioned adipose-derived mesenchymal stem cells with photobiomodulation for the treatment of diabetic foot ulcers: a systematic review. Lasers Med Sci 2021; 37:1415-1425. [PMID: 34697696 DOI: 10.1007/s10103-021-03451-6] [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: 08/30/2021] [Accepted: 10/19/2021] [Indexed: 10/20/2022]
Abstract
The primary goal of this systematic review article was to provide an outline of the use of diabetic autologous adipose-derived mesenchymal stem cells (DAAD-MSCs) in the treatment of wounds and ulcers in animal models and patients with diabetes mellitus (DM). The secondary goal was to present the outcomes of pretreatment of diabetic adipose-derived mesenchymal stem cells (DAD-MSCs) with probable different agents in the treatment of diabetic foot ulcers (DFUs) and wounds. In view of possible clinical applications of AD-MSC-mediated cell therapy for DFUs, it is essential to evaluate the influence of DM on AD-MSC functions. Nevertheless, there are conflicting results about the effects of DAAD-MSCs on accelerating wound healing in animals and DM patients. Multistep research of the MEDLINE, PubMed, Embase, Clinicaltrials.gov, Scopus database, and Cochrane databases was conducted for abstracts and full-text scientific papers published between 2000 and 2020. Finally, 5 articles confirmed that the usage of allogeneic or autologous AD-MSCs had encouraging outcomes on diabetic wound healing. One study reported that DM changes AD-MSC function and therapeutic potential, and one article recommended that the pretreatment of diabetic allogeneic adipose-derived mesenchymal stem cells (DAlD-MSCs) was more effective in accelerating diabetic wound healing. Recently, much work has concentrated on evolving innovative healing tactics for hastening the repair of DFUs. While DM alters the intrinsic properties of AD-MSCs and impairs their function, one animal study showed that the pretreatment of DAlD-MSCs in vitro significantly increased the function of DAlD-MSCs compared with DAlD-MSCs without any treatment. Preconditioning diabetic AD-MSCs with pretreatment agents like photobiomodulation (PBM) significantly hastened healing in delayed-healing wounds. It is suggested that further animal and human studies be conducted in order to provide more documentation. Hopefully, these outcomes will help the use of DAAD-MSCs plus PBM as a routine treatment protocol for healing severe DFUs in DM patients.
Collapse
|
12
|
Chen Z, Ge Y, Zhou L, Li T, Yan B, Chen J, Huang J, Du W, Lv S, Tong P, Shan L. Pain relief and cartilage repair by Nanofat against osteoarthritis: preclinical and clinical evidence. Stem Cell Res Ther 2021; 12:477. [PMID: 34446107 PMCID: PMC8390235 DOI: 10.1186/s13287-021-02538-9] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2021] [Accepted: 08/05/2021] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Osteoarthritis (OA) is the most common joint degenerative disorder, with little effective therapy to date. Nanofat is a cocktail of cells obtained from fat tissue, which possesses regenerative capacity and has a potential in treating OA. This study aimed to determine the anti-OA efficacy of Nanofat from basic and clinical aspects and explore its action mode. METHODS Flow cytometry was performed to characterize Nanofat. A monoiodoacetate-induced OA rat model was employed for in vivo study. Cell viability and wound healing assays were conducted for in vitro study. Real-time PCR and Western blot assays were applied to explore the molecular action mode of Nanofat. Moreover, a retrospective analysis was conducted to determine the clinical efficacy and safety of Nanofat on knee OA patients. RESULTS The in vivo results showed that Nanofat significantly attenuated pain symptoms and protected cartilage ECM (Col2) from damage, and its effects were not significantly differed with adipose tissue-derived stem cells (both P > 0.05). The in vitro results showed that Nanofat promoted the cell viability and migration of chondrocytes and significantly restored the IL-1β-induced abnormal gene expressions of Col2, Aggrecan, Sox9, Adamts5, Mmp3, Mmp9 Mmp13, IL-6 and Col10 and protein expressions of Col2, MMP9, MMP13, and Sox9 of chondrocytes. The regulatory actions of Nanofat on these anabolic, catabolic, and hypertrophic molecules of chondrocytes were similar between two treatment routes: co-culture and conditioned medium, suggesting a paracrine-based mode of action of Nanofat. Moreover, the clinical data showed that Nanofat relieved pain and repaired damaged cartilage of OA patients, with no adverse events. CONCLUSION In sum, this study demonstrated the anti-OA efficacy as well as a paracrine-based action mode of Nanofat, providing novel knowledge of Nanofat and suggesting it as a promising and practical cell therapy for clinical treatment of OA.
Collapse
Affiliation(s)
- Zuxiang Chen
- The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, 310053, Zhejiang, People's Republic of China
| | - Yanzhi Ge
- The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, 310053, Zhejiang, People's Republic of China
| | - Li Zhou
- The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, 310053, Zhejiang, People's Republic of China
| | - Ting Li
- The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, Zhejiang, People's Republic of China
| | - Bo Yan
- Cell Resource Bank and Integrated Cell Preparation Center of Xiaoshan District, Hangzhou Regional Cell Preparation Center (Sanjiang Shangyu Biotechnology Co., Ltd), Hangzhou, People's Republic of China
| | - Junjie Chen
- The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, 310053, Zhejiang, People's Republic of China
| | - Jiefeng Huang
- The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, 310053, Zhejiang, People's Republic of China
| | - Wenxi Du
- The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, 310053, Zhejiang, People's Republic of China
| | - Shuaijie Lv
- The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, 310053, Zhejiang, People's Republic of China.
| | - Peijian Tong
- The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, 310053, Zhejiang, People's Republic of China.
| | - Letian Shan
- The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, 310053, Zhejiang, People's Republic of China.
- Cell Resource Bank and Integrated Cell Preparation Center of Xiaoshan District, Hangzhou Regional Cell Preparation Center (Sanjiang Shangyu Biotechnology Co., Ltd), Hangzhou, People's Republic of China.
| |
Collapse
|
13
|
Blaszczak AM, Jalilvand A, Hsueh WA. Adipocytes, Innate Immunity and Obesity: A Mini-Review. Front Immunol 2021; 12:650768. [PMID: 34248937 PMCID: PMC8264354 DOI: 10.3389/fimmu.2021.650768] [Citation(s) in RCA: 65] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2021] [Accepted: 04/28/2021] [Indexed: 12/12/2022] Open
Abstract
The role of adipose tissue (AT) inflammation in obesity and its multiple related-complications is a rapidly expanding area of scientific interest. Within the last 30 years, the role of the adipocyte as an endocrine and immunologic cell has been progressively established. Like the macrophage, the adipocyte is capable of linking the innate and adaptive immune system through the secretion of adipokines and cytokines; exosome release of lipids, hormones, and microRNAs; and contact interaction with other immune cells. Key innate immune cells in AT include adipocytes, macrophages, neutrophils, and innate lymphoid cells type 2 (ILC2s). The role of the innate immune system in promoting adipose tissue inflammation in obesity will be highlighted in this review. T cells and B cells also play important roles in contributing to AT inflammation and are discussed in this series in the chapter on adaptive immunity.
Collapse
Affiliation(s)
- Alecia M Blaszczak
- Hsueh Laboratory, The Ohio State University Wexner Medical Center, Diabetes and Metabolism Research Center, Columbus, OH, United States
| | - Anahita Jalilvand
- Hsueh Laboratory, The Ohio State University Wexner Medical Center, Diabetes and Metabolism Research Center, Columbus, OH, United States
| | - Willa A Hsueh
- Hsueh Laboratory, The Ohio State University Wexner Medical Center, Diabetes and Metabolism Research Center, Columbus, OH, United States
| |
Collapse
|
14
|
Skin Immunomodulation during Regeneration: Emerging New Targets. J Pers Med 2021; 11:jpm11020085. [PMID: 33573342 PMCID: PMC7911085 DOI: 10.3390/jpm11020085] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Revised: 12/25/2020] [Accepted: 01/07/2021] [Indexed: 02/08/2023] Open
Abstract
Adipose-Derived Stem Cells (ADSC) are present within the hypodermis and are also expected to play a pivotal role in wound healing, immunomodulation, and rejuvenation activities. They orchestrate, through their exosome, the mechanisms associated to cell differentiation, proliferation, and cell migration by upregulating genes implicated in different functions including skin barrier, immunomodulation, cell proliferation, and epidermal regeneration. ADSCs directly interact with their microenvironment and specifically the immune cells, including macrophages and T and B cells, resulting in differential inflammatory and anti-inflammatory mechanisms impacting, in return, ADSCs microenvironment and thus skin function. These useful features of ADSCs are involved in tissue repair, where the required cell proliferation, angiogenesis, and anti-inflammatory responses should occur rapidly in damaged sites. Different pathways involved have been reported such as Growth Differentiation Factor-11 (GDF11), Tumor Growth Factor (TGF)-β, Metalloproteinase (MMP), microRNA, and inflammatory cytokines that might serve as specific biomarkers of their immunomodulating capacity. In this review, we try to highlight ADSCs’ network and explore the potential indicators of their immunomodulatory effect in skin regeneration and aging. Assessment of these biomarkers might be useful and should be considered when designing new clinical therapies using ADSCs or their specific exosomes focusing on their immunomodulation activity.
Collapse
|
15
|
Extracellular Vesicles from Adipose Tissue Stem Cells in Diabetes and Associated Cardiovascular Disease; Pathobiological Impact and Therapeutic Potential. Int J Mol Sci 2020; 21:ijms21249598. [PMID: 33339409 PMCID: PMC7766415 DOI: 10.3390/ijms21249598] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2020] [Revised: 12/11/2020] [Accepted: 12/14/2020] [Indexed: 02/07/2023] Open
Abstract
Adipose tissue-derived stem cells (ADSCs) are pluripotent mesenchymal stem cells found in relatively high percentages in the adipose tissue and able to self-renew and differentiate into many different types of cells. “Extracellular vesicles (EVs), small membrane vesicular structures released during cell activation, senescence, or apoptosis, act as mediators for long distance communication between cells, transferring their specific bioactive molecules into host target cells”. There is a general consensus on how to define and isolate ADSCs, however, multiple separation and characterization protocols are being used in the present which complicate the results’ integration in a single theory on ADSCs’ and their derived factors’ way of action. Metabolic syndrome and type 2 diabetes mellitus (T2DM) are mainly caused by abnormal adipose tissue size, distribution and metabolism and so ADSCs and their secretory factors such as EVs are currently investigated as therapeutics in these diseases. Moreover, due to their relatively easy isolation and propagation in culture and their differentiation ability, ADSCs are being employed in preclinical studies of implantable devices or prosthetics. This review aims to provide a comprehensive summary of the current knowledge on EVs secreted from ADSCs both as diagnostic biomarkers and therapeutics in diabetes and associated cardiovascular disease, the molecular mechanisms involved, as well as on the use of ADSC differentiation potential in cardiovascular tissue repair and prostheses.
Collapse
|
16
|
Ahmadi H, Amini A, Fadaei Fathabady F, Mostafavinia A, Zare F, Ebrahimpour-malekshah R, Ghalibaf MN, Abrisham M, Rezaei F, Albright R, Ghoreishi SK, Chien S, Bayat M. Transplantation of photobiomodulation-preconditioned diabetic stem cells accelerates ischemic wound healing in diabetic rats. Stem Cell Res Ther 2020; 11:494. [PMID: 33239072 PMCID: PMC7688005 DOI: 10.1186/s13287-020-01967-2] [Citation(s) in RCA: 43] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2020] [Accepted: 10/07/2020] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Diabetic foot ulcer is the most costly and complex challenge for patients with diabetes. We hereby assessed the effectiveness of different preconditioned adipose-derived mesenchymal stem cells (AD-MSCs) and photobiomodulation protocols on treating an infected ischemic wound in type 1 diabetic rats. METHODS There were five groups of rats: (1) control, (2) control AD-MSCs [diabetic AD-MSCs were transplanted (grafted) into the wound bed], (3) AD-MSC + photobiomodulation in vivo (diabetic AD-MSCs were grafted into the wound, followed by in vivo PBM treatment), (4) AD-MSCs + photobiomodulation in vitro, and (5) AD-MSCs + photobiomodulation in vitro + in vivo. RESULTS Diabetic AD-MSCs preconditioned with photobiomodulation had significantly risen cell function compared to diabetic AD-MSC. Groups 3 and 5 had significantly decreased microbial flora correlated to groups 1 and 2 (all, p = 0.000). Groups 2, 3, 4, and 5 had significantly improved wound closure rate (0.4, 0.4, 0.4, and 0.8, respectively) compared to group 1 (0.2). Groups 2-5 had significantly increased wound strength compared to group 1 (all p = 0.000). In most cases, group 5 had significantly better results than groups 2, 3, and 4. CONCLUSIONS Preconditioning diabetic AD-MSCs with photobiomodulation in vitro plus photobiomodulation in vivo significantly hastened healing in the diabetic rat model of an ischemic infected delayed healing wound.
Collapse
Affiliation(s)
- Houssein Ahmadi
- Department of Biology and Anatomical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Abdollah Amini
- Department of Biology and Anatomical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Fatemeh Fadaei Fathabady
- Department of Biology and Anatomical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Atarodsadat Mostafavinia
- Department of Anatomy, Faculty of Medicine, Tehran Medical sciences, Islamic Azad University, Tehran, Iran
| | - Fatemeh Zare
- Department of Biology and Anatomical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | - Mustafa Neshat Ghalibaf
- Department of Biology and Anatomical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Matin Abrisham
- Department of Biology and Anatomical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Fatemehalsadat Rezaei
- University of Kentucky, College of Pharmacy, 789 South Limestone, Lexington, Kentucky 40536 USA
| | | | | | - Sufan Chien
- Price Institute of Surgical Research, University of Louisville, and Noveratech LLC, Louisville, KY USA
| | - Mohammad Bayat
- Department of Biology and Anatomical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Price Institute of Surgical Research, University of Louisville, and Noveratech LLC, Louisville, KY USA
| |
Collapse
|
17
|
Abstract
Buerger’s disease or Thromboangiitis Obliterans (TAO) is a nonatherosclerotic segmental vascular disease which affects small and medium arteries and veins in the upper and lower extremities. Based on pathological findings, TAO can be considered as a distinct form of vasculitis that is most prevalent in young male smokers. There is no definitive cure for this disease as therapeutic modalities are limited in number and efficacy. Surgical bypass has limited utility and 24% of patients will ultimately require amputation. Recently, studies have shown that therapeutic angiogenesis and immunomodulatory approaches through the delivery of stem cells to target tissues are potential options for ischemic lesion treatment. In this review, we summarize the current knowledge of TAO treatment and provide an overview of stem cell-based treatment modalities.
Collapse
|
18
|
Osipova OS, Saaia SB, Karpenko AA, Zakiian SM. [Problems and prospects of cell therapy for critical ischaemia of lower limbs]. ANGIOLOGII︠A︡ I SOSUDISTAI︠A︡ KHIRURGII︠A︡ = ANGIOLOGY AND VASCULAR SURGERY 2020; 26:23-33. [PMID: 32597882 DOI: 10.33529/angio2020220] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND Cell therapy was proposed as a procedure of indirect revascularization for patients with critical ischaemia of lower extremities for whom endovascular and surgical revascularization is impossible. We present herein a review of the state of the art of studies in the field of cell therapy of this cohort of patients. BASIC PROVISIONS Cell therapy has proved safe, however, the results of studies of efficacy are relatively ambiguous and unconvincing. The number of patients in separately taken clinical trials is minimal. The reviewed studies differed not only by heterogeneity of the cell types used but by the routes of administration of cells (cells were delivered either intramuscularly (predominantly) or intraarterially) and the duration of follow up (time of assessment and duration of follow up varied from 1 month to 2 years). One of the problems became the lack of the routine study of the angiogenic potential of stem cells prior to their clinical application. It is known that the angiogenic activity of multipotent cells of apparently healthy patients may differ from that of patients suffering from atherosclerosis, chronic renal failure, diabetes. CONCLUSIONS It is supposed that treatment with stem cells or precursor cells is more efficient as compared to protein or gene therapy not only owing to direct vasculogenic properties but a paracrine action through excretion of proangiogenic biologically active substances. More studies with larger cohorts are necessary to provide stronger safety and efficacy data on cell therapy. Besides, a promising trend in the field of cellular approaches is modulation of regenerative capability of stem cells, which may help overcome difficulties in understanding the place of cell therapy in therapeutic angiogenesis.
Collapse
Affiliation(s)
- O S Osipova
- Department of Vascular Pathology and Hybrid Surgery, National Medical Research Centre named after Academician Meshalkin E.N. under the RF Ministry of Public Health, Novosibirsk, Russia
| | - Sh B Saaia
- Department of Vascular Pathology and Hybrid Surgery, National Medical Research Centre named after Academician Meshalkin E.N. under the RF Ministry of Public Health, Novosibirsk, Russia
| | - A A Karpenko
- Department of Vascular Pathology and Hybrid Surgery, National Medical Research Centre named after Academician Meshalkin E.N. under the RF Ministry of Public Health, Novosibirsk, Russia
| | - S M Zakiian
- Department of Vascular Pathology and Hybrid Surgery, National Medical Research Centre named after Academician Meshalkin E.N. under the RF Ministry of Public Health, Novosibirsk, Russia
| |
Collapse
|
19
|
Effect of Hypoxia Preconditioned Secretomes on Lymphangiogenic and Angiogenic Sprouting: An in Vitro Analysis. Biomedicines 2020; 8:biomedicines8090365. [PMID: 32962277 PMCID: PMC7555444 DOI: 10.3390/biomedicines8090365] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2020] [Revised: 09/17/2020] [Accepted: 09/19/2020] [Indexed: 12/22/2022] Open
Abstract
Hypoxia Preconditioned Plasma (HPP) and Serum (HPS) are two blood-derived autologous growth factor compositions that are being clinically employed as tools for promoting tissue regeneration, and have been extensively examined for their angiogenic activity. As yet, their ability to stimulate/support lymphangiogenesis remains unknown, although this is an important but often-neglected process in wound healing and tissue repair. Here we set out to characterize the potential of hypoxia preconditioned secretomes as promoters of angiogenic and lymphangiogenic sprouting in vitro. We first analysed HPP/HPS in terms of pro- (VEGF-C) and anti- (TSP-1, PF-4) angiogenic/lymphangiogenic growth factor concentration, before testing their ability to stimulate microvessel sprouting in the mouse aortic ring assay and lymphatic sprouting in the thoracic duct ring assay. The origin of lymphatic structures was validated with lymph-specific immunohistochemical staining (Anti-LYVE-1) and lymphatic vessel-associated protein (polydom) quantification in culture supernatants. HPP/HPS induced greater angiogenic and lymphatic sprouting compared to non-hypoxia preconditioned samples (normal plasma/serum), a response that was compatible with their higher VEGF-C concentration. These findings demonstrate that hypoxia preconditioned blood-derived secretomes have the ability to not only support sprouting angiogenesis, but also lymphangiogenesis, which underlines their multimodal regenerative potential.
Collapse
|
20
|
Mazini L, Rochette L, Malka G. Adipose-Derived Stem Cells (ADSCs) and Growth Differentiation Factor 11 (GDF11): Regenerative and Antiaging Capacity for the Skin. Regen Med 2020. [DOI: 10.5772/intechopen.91233] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
|
21
|
Fan X, Li K, Zhu L, Deng X, Feng Z, Xu C, Liu S, Wu J. Prolonged therapeutic effects of photoactivated adipose-derived stem cells following ischaemic injury. Acta Physiol (Oxf) 2020; 230:e13475. [PMID: 32306486 DOI: 10.1111/apha.13475] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2019] [Revised: 03/31/2020] [Accepted: 04/06/2020] [Indexed: 12/13/2022]
Abstract
AIM Adipose-derived stem cells (ASCs) therapies are emerging as a promising approach to therapeutic angiogenesis. Therapeutic persistence and reduced primitive stem cell function following cell delivery remains a critical hurdle for the clinical translation of stem cells in current approaches. METHODS Cultured ASCs were derived from subcutaneous white adipose tissue isolated from mice fed a normal diet (ND). Unilateral hindlimb ischaemia model was induced in high-fat diet (HFD)-fed mice by femoral artery interruption, after which photoactivated and non-light-treated ASCs were injected into the tail vein of mice. Laser Doppler imaging was conducted to measure the blood flow reperfusion. Capillary density was measured in the ischaemic gastrocnemius muscle. mRNA levels of angiogenic factors were determined by reverse-transcription polymerase chain reaction. Flow cytometry was used to determine the characterization of ASCs and endothelial progenitor cell (EPC). Human ASCs secretomes were analysed by liquid chromatography tandem mass spectrometry. RESULTS Our study demonstrated that photoactivated ND-ASCs prolonged functional blood flow perfusion and increased ASCs-derived EPC and neovascularization 38 days after ligation, when compared with saline-treated controls. Profiling analysis in ischaemic muscles showed upregulation of genes associated with pro-angiogenic factors after injection of photoactivated ND-ASCs when compared with the non-light-treated ASCs or saline treated HFD mice. Mass spectrometry revealed that light-treated ASCs conditioned medium retained a more complete pro-angiogenic activity with significant upregulation of angiogenesis related proteins. CONCLUSION Our data demonstrates that photoactivated ND-ASCs improve blood flow recovery and their injection may prove to be a useful strategy for the prevention and treatment of diabetic peripheral arterial disease.
Collapse
Affiliation(s)
- Xin Fan
- Key Laboratory of Medical Electrophysiology of Ministry of Education Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease of Sichuan Province Drug Discovery Research Center Southwest Medical University Luzhou China
- Laboratory for Cardiovascular Pharmacology Department of Pharmacology School of Pharmacy Southwest Medical University Luzhou China
| | - Kai Li
- Key Laboratory of Medical Electrophysiology of Ministry of Education Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease of Sichuan Province Drug Discovery Research Center Southwest Medical University Luzhou China
- Laboratory for Cardiovascular Pharmacology Department of Pharmacology School of Pharmacy Southwest Medical University Luzhou China
| | - Luochen Zhu
- Key Laboratory of Medical Electrophysiology of Ministry of Education Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease of Sichuan Province Drug Discovery Research Center Southwest Medical University Luzhou China
- Laboratory for Cardiovascular Pharmacology Department of Pharmacology School of Pharmacy Southwest Medical University Luzhou China
| | - Xin Deng
- Key Laboratory of Medical Electrophysiology of Ministry of Education Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease of Sichuan Province Drug Discovery Research Center Southwest Medical University Luzhou China
- Laboratory for Cardiovascular Pharmacology Department of Pharmacology School of Pharmacy Southwest Medical University Luzhou China
| | - Ziqian Feng
- Key Laboratory of Medical Electrophysiology of Ministry of Education Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease of Sichuan Province Drug Discovery Research Center Southwest Medical University Luzhou China
- Laboratory for Cardiovascular Pharmacology Department of Pharmacology School of Pharmacy Southwest Medical University Luzhou China
| | - Chunrong Xu
- Key Laboratory of Medical Electrophysiology of Ministry of Education Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease of Sichuan Province Drug Discovery Research Center Southwest Medical University Luzhou China
- Laboratory for Cardiovascular Pharmacology Department of Pharmacology School of Pharmacy Southwest Medical University Luzhou China
| | - Sijing Liu
- Key Laboratory of Medical Electrophysiology of Ministry of Education Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease of Sichuan Province Drug Discovery Research Center Southwest Medical University Luzhou China
- Laboratory for Cardiovascular Pharmacology Department of Pharmacology School of Pharmacy Southwest Medical University Luzhou China
| | - Jianbo Wu
- Key Laboratory of Medical Electrophysiology of Ministry of Education Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease of Sichuan Province Drug Discovery Research Center Southwest Medical University Luzhou China
- Laboratory for Cardiovascular Pharmacology Department of Pharmacology School of Pharmacy Southwest Medical University Luzhou China
| |
Collapse
|
22
|
Fujiwara O, Prasai A, Perez-Bello D, El Ayadi A, Petrov IY, Esenaliev RO, Petrov Y, Herndon DN, Finnerty CC, Prough DS, Enkhbaatar P. Adipose-derived stem cells improve grafted burn wound healing by promoting wound bed blood flow. BURNS & TRAUMA 2020; 8:tkaa009. [PMID: 32346539 PMCID: PMC7175768 DOI: 10.1093/burnst/tkaa009] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/17/2020] [Revised: 01/22/2020] [Accepted: 01/30/2000] [Indexed: 01/08/2023]
Abstract
BACKGROUND Researchers have explored the use of adipose-derived stem cells (ASCs) as a cell-based therapy to cover wounds in burn patients; however, underlying mechanistic aspects are not completely understood. We hypothesized that ASCs would improve post-burn wound healing after eschar excision and grafting by increasing wound blood flow via induction of angiogenesis-related pathways. METHODS To test the hypothesis, we used an ovine burn model. A 5 cm2 full thickness burn wound was induced on each side of the dorsum. After 24 hours, the burned skin was excised and a 2 cm2 patch of autologous donor skin was grafted. The wound sites were randomly allocated to either topical application of 7 million allogeneic ASCs or placebo treatment (phosphate-buffered saline [PBS]). Effects of ASCs culture media was also compared to those of PBS. Wound healing was assessed at one and two weeks following the application of ASCs. Allogeneic ASCs were isolated, cultured and characterized from non-injured healthy sheep. The identity of the ASCs was confirmed by flow cytometry analysis, differentiation into multiple lineages and gene expression via real-time polymerase chain reaction. Wound blood flow, epithelialization, graft size and take and the expression of vascular endothelial growth factor (VEGF) were determined via enzyme-linked immunosorbent assay and Western blot. RESULTS Treatment with ASCs accelerated the patch graft growth compared to the control (p < 0.05). Topical application of ASCs significantly increased wound blood flow (p < 0.05). Expression of VEGF was significantly higher in the wounds treated with ASCs compared to control (p < 0.05). CONCLUSIONS ASCs accelerated grafted skin growth possibly by increasing the blood flow via angiogenesis induced by a VEGF-dependent pathway.
Collapse
Affiliation(s)
- Osamu Fujiwara
- Department of Anesthesiology, University of Texas Medical Branch, Galveston, TX, USA
| | - Anesh Prasai
- Department of Surgery, University of Texas Medical Branch, Galveston, 301 University BLVD TX 77555, USA
- Shriners Hospitals for Children – Galveston, 815 Market Street Galveston, TX 77555, USA
| | - Dannelys Perez-Bello
- Department of Anesthesiology, University of Texas Medical Branch, Galveston, TX, USA
| | - Amina El Ayadi
- Department of Surgery, University of Texas Medical Branch, Galveston, 301 University BLVD TX 77555, USA
- Shriners Hospitals for Children – Galveston, 815 Market Street Galveston, TX 77555, USA
- Sealy Center for Molecular Medicine, and the Institute for Translational Sciences, University of Texas Medical Branch, 301 University BLVD Galveston, TX 77555, USA
| | - Irene Y Petrov
- Center for Biomedical Engineering, University of Texas Medical Branch, 601 Harbor Side Dr. Galveston, TX 77555, USA
| | - Rinat O Esenaliev
- Department of Anesthesiology, University of Texas Medical Branch, Galveston, TX, USA
- Center for Biomedical Engineering, University of Texas Medical Branch, 601 Harbor Side Dr. Galveston, TX 77555, USA
- Department of Neuroscience, Cell Biology, and Anatomy, University of Texas Medical Branch, 301 University BLVD Galveston, TX 77555, USA
| | - Yuriy Petrov
- Center for Biomedical Engineering, University of Texas Medical Branch, 601 Harbor Side Dr. Galveston, TX 77555, USA
| | - David N Herndon
- Department of Surgery, University of Texas Medical Branch, Galveston, 301 University BLVD TX 77555, USA
- Shriners Hospitals for Children – Galveston, 815 Market Street Galveston, TX 77555, USA
| | - Celeste C Finnerty
- Department of Surgery, University of Texas Medical Branch, Galveston, 301 University BLVD TX 77555, USA
- Shriners Hospitals for Children – Galveston, 815 Market Street Galveston, TX 77555, USA
- Sealy Center for Molecular Medicine, and the Institute for Translational Sciences, University of Texas Medical Branch, 301 University BLVD Galveston, TX 77555, USA
| | - Donald S Prough
- Department of Anesthesiology, University of Texas Medical Branch, Galveston, TX, USA
| | - Perenlei Enkhbaatar
- Department of Anesthesiology, University of Texas Medical Branch, Galveston, TX, USA
- Shriners Hospitals for Children – Galveston, 815 Market Street Galveston, TX 77555, USA
| |
Collapse
|
23
|
Bayat M, Chien S. Combined Adipose-Derived Mesenchymal Stem Cells and Photobiomodulation Could Modulate the Inflammatory Response and Treat Infected Diabetic Foot Ulcers. Photobiomodul Photomed Laser Surg 2020; 38:135-137. [PMID: 31638476 DOI: 10.1089/photob.2019.4670] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Affiliation(s)
- Mohammad Bayat
- Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Price Institute of Surgical Research, University of Louisville, Louisville, Kentucky
- Noveratech LLC of Louisville, Louisville, Kentucky
| | - Sufan Chien
- Price Institute of Surgical Research, University of Louisville, Louisville, Kentucky
- Noveratech LLC of Louisville, Louisville, Kentucky
| |
Collapse
|
24
|
Mazini L, Rochette L, Admou B, Amal S, Malka G. Hopes and Limits of Adipose-Derived Stem Cells (ADSCs) and Mesenchymal Stem Cells (MSCs) in Wound Healing. Int J Mol Sci 2020; 21:E1306. [PMID: 32075181 PMCID: PMC7072889 DOI: 10.3390/ijms21041306] [Citation(s) in RCA: 314] [Impact Index Per Article: 62.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2019] [Revised: 01/14/2020] [Accepted: 01/20/2020] [Indexed: 12/11/2022] Open
Abstract
Adipose tissue derived stem cells (ADSCs) are mesenchymal stem cells identified within subcutaneous tissue at the base of the hair follicle (dermal papilla cells), in the dermal sheets (dermal sheet cells), in interfollicular dermis, and in the hypodermis tissue. These cells are expected to play a major role in regulating skin regeneration and aging-associated morphologic disgraces and structural deficits. ADSCs are known to proliferate and differentiate into skin cells to repair damaged or dead cells, but also act by an autocrine and paracrine pathway to activate cell regeneration and the healing process. During wound healing, ADSCs have a great ability in migration to be recruited rapidly into wounded sites added to their differentiation towards dermal fibroblasts (DF), endothelial cells, and keratinocytes. Additionally, ADSCs and DFs are the major sources of the extracellular matrix (ECM) proteins involved in maintaining skin structure and function. Their interactions with skin cells are involved in regulating skin homeostasis and during healing. The evidence suggests that their secretomes ensure: (i) The change in macrophages inflammatory phenotype implicated in the inflammatory phase, (ii) the formation of new blood vessels, thus promoting angiogenesis by increasing endothelial cell differentiation and cell migration, and (iii) the formation of granulation tissues, skin cells, and ECM production, whereby proliferation and remodeling phases occur. These characteristics would be beneficial to therapeutic strategies in wound healing and skin aging and have driven more insights in many clinical investigations. Additionally, it was recently presented as the tool key in the new free-cell therapy in regenerative medicine. Nevertheless, ADSCs fulfill the general accepted criteria for cell-based therapies, but still need further investigations into their efficiency, taking into consideration the host-environment and patient-associated factors.
Collapse
Affiliation(s)
- Loubna Mazini
- Laboratoire Cellules Souches et Régénération Cellulaire et Tissulaire, Centre interface Applications Médicales (CIAM), Université Mohammed VI Polytechnique, Ben-Guerir 43 150, Morocco;
| | - Luc Rochette
- Equipe d’Accueil (EA 7460), Physiopathologie et Epidémiologie Cérébro-Cardiovasculaires (PEC2), Faculté des Sciences de Santé Université de Bourgogne—Franche Comté, 7 Bd Jeanne d’Arc, 21000 Dijon, France;
| | - Brahim Admou
- Laboratoire d’immunologie, Centre de Recherche Clinique, Faculté de Médecine et Pharmacie, Université Cadi Ayyad, Centre Hospitalier Universitaire, Marrakech 40 000, Morocco;
| | - Said Amal
- Service de dermatologie, Faculté de Médecine et Pharmacie, Université Cadi Ayyad, Centre hospitalier universitaire, Marrakech 40000, Morocco;
| | - Gabriel Malka
- Laboratoire Cellules Souches et Régénération Cellulaire et Tissulaire, Centre interface Applications Médicales (CIAM), Université Mohammed VI Polytechnique, Ben-Guerir 43 150, Morocco;
| |
Collapse
|
25
|
The Roles of Podoplanin-Positive/Podoplanin-Negative Cells from Adipose-Derived Stem Cells in Lymphatic Regeneration. Plast Reconstr Surg 2020; 145:420-431. [DOI: 10.1097/prs.0000000000006474] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
|
26
|
Ebrahimpour-Malekshah R, Amini A, Zare F, Mostafavinia A, Davoody S, Deravi N, Rahmanian M, Hashemi SM, Habibi M, Ghoreishi SK, Chien S, Shafikhani S, Ahmadi H, Bayat S, Bayat M. Combined therapy of photobiomodulation and adipose-derived stem cells synergistically improve healing in an ischemic, infected and delayed healing wound model in rats with type 1 diabetes mellitus. BMJ Open Diabetes Res Care 2020; 8:e001033. [PMID: 32098898 PMCID: PMC7206914 DOI: 10.1136/bmjdrc-2019-001033] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2019] [Revised: 12/16/2019] [Accepted: 12/26/2019] [Indexed: 12/20/2022] Open
Abstract
OBJECTIVE We assessed the therapeutic effects of photobiomodulation (PBM) and adipose-derived stem cell (ADS) treatments individually and together on the maturation step of repairing of a delayed healing wound model in rats with type 1 diabetes mellitus (DM1). RESEARCH DESIGN AND METHODS We randomly assigned 24 rats with DM1 to four groups (n=6 per group). Group 1 was the control (placebo) group. In group 2, allograft human ADSs were transplanted. Group 3 was subjected to PBM (wavelength: 890 nm, peak power output: 80 W, pulse frequency: 80 Hz, pulsed duration: 180 ns, duration of exposure for each point: 200 s, power density: 0.001 W/cm2, energy density: 0.2 J/cm2) immediately after surgery, which continued for 6 days per week for 16 days. Group 4 received both the human ADS and PBM. In addition, we inflicted an ischemic, delayed healing, and infected wound simulation in all of the rats. The wounds were infected with methicillin-resistant Staphylococcus aureus (MRSA). RESULTS All three treatment regimens significantly decreased the amount of microbial flora, significantly increased wound strength and significantly modulated inflammatory response and significantly increased angiogenesis on day 16. Microbiological analysis showed that PBM+ADS was significantly better than PBM and ADS alone. In terms of wound closure rate and angiogenesis, PBM+ADS was significantly better than the PBM, ADS and control groups. CONCLUSIONS Combination therapy of PBM+ADS is more effective that either PBM or ADS in stimulating skin injury repair, and modulating inflammatory response in an MRSA-infected wound model of rats with DM1.
Collapse
Affiliation(s)
- Roohollah Ebrahimpour-Malekshah
- Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Abdollah Amini
- Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Fatemeh Zare
- Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Atarodsadat Mostafavinia
- Department of Anatomy, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Samin Davoody
- Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Niloofar Deravi
- Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Rahmanian
- Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Seyed Mahmoud Hashemi
- Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Urogenital Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Malihe Habibi
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | - Sufan Chien
- Price Institute of Surgical Research, University of Louisville, and Noveratech LLC of Louisville, Louisville, Kentucky, USA
| | - Sasha Shafikhani
- Department of Medicine, Division of Hematology/Oncology, Department of Immunology and Microbiology, Cancer Center, Rush University Medical Center, Chicago, Illinois, USA
| | - Houssein Ahmadi
- Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sahar Bayat
- Illinois Institute of Technology, Chicago, Illinois, USA
| | - Mohammad Bayat
- Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Price Institute of Surgical Research, University of Louisville, and Noveratech LLC of Louisville, Louisville, Kentucky, USA
| |
Collapse
|
27
|
Moradi A, Zare F, Mostafavinia A, Safaju S, Shahbazi A, Habibi M, Abdollahifar MA, Hashemi SM, Amini A, Ghoreishi SK, Chien S, Hamblin MR, Kouhkheil R, Bayat M. Photobiomodulation plus Adipose-derived Stem Cells Improve Healing of Ischemic Infected Wounds in Type 2 Diabetic Rats. Sci Rep 2020; 10:1206. [PMID: 31988386 PMCID: PMC6985227 DOI: 10.1038/s41598-020-58099-z] [Citation(s) in RCA: 41] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2019] [Accepted: 12/31/2019] [Indexed: 12/21/2022] Open
Abstract
In this study, we sought to investigate the impact of photobiomodulation and adipose-derived stem cells (ADS), alone and in combination, on the maturation step of wound healing in an ischemic infected delayed healing wound model in rats with type 2 diabetes mellitus (DM2). We randomly divided 24 adult male rats into 4 groups (n = 6 per group). DM2 plus an ischemic delayed healing wound were induced in all rats. The wounds were infected with methicillin-resistant Staphylococcus aureus. Group 1 was the control (placebo) group. Group 2 received only photobiomodulation (890 nm, 80 Hz, 0.324 J/cm2, and 0.001 W/cm2). Group 3 received only the allograft ADS. Group 4 received allograft ADS followed by photobiomodulation. On days 0, 4, 8, 12, and 16, we performed microbiological examination (colony forming units, [CFU]), wound area measurement, wound closure rate, wound strength, and histological and stereological examinations. The results indicated that at day 16, there was significantly decreased CFU (Analysis of variance, p = 0.001) in the photobiomodulation + ADS (0.0 ± 0.0), ADS (1350 ± 212), and photobiomodulation (0.0 ± 0.0) groups compared with the control group (27250 ± 1284). There was significantly decreased wound area (Analysis of variance, p = 0.000) in the photobiomodulation + ADS (7.4 ± 1.4 mm2), ADS (11 ± 2.2 mm2), and photobiomodulation (11.4 ± 1.4 mm2) groups compared with the control group (25.2 ± 1.7). There was a significantly increased tensiometeric property (stress maximal load, Analysis of variance, p = 0.000) in the photobiomodulation + ADS (0.99 ± 0.06 N/cm2), ADS (0.51 ± 0.12 N/cm2), and photobiomodulation (0.35 ± 0.15 N/cm2) groups compared with the control group (0.18 ± 0.04). There was a significantly modulated inflammatory response in (Analysis of variance, p = 0.049) in the photobiomodulation + ADS (337 ± 96), ADS (1175 ± 640), and photobiomodulation (69 ± 54) treatments compared to control group (7321 ± 4099). Photobiomodulation + ADS gave significantly better improvements in CFU, wound area, and wound strength compared to photobiomodulation or ADS alone. Photobiomodulation, ADS, and their combination significantly hastened healing in ischemic methicillin-resistant Staphylococcus aureus infected delayed healing wounds in rats with DM2. Combined application of photobiomodulation plus ADS demonstrated an additive effect.
Collapse
Affiliation(s)
- Ali Moradi
- Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Fatemeh Zare
- Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Atarodsadat Mostafavinia
- Department of Anatomy, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad university, Tehran, Iran
| | - Sobhan Safaju
- Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Amirhossein Shahbazi
- Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Malihe Habibi
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad-Amin Abdollahifar
- Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Seyed Mahmoud Hashemi
- Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Urogenital Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Abdollah Amini
- Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | - Sufan Chien
- Price Institute of Surgical Research, University of Louisville and Noveratech LLC of Louisville, Louisville, KY, USA
| | - Michael R Hamblin
- Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Reza Kouhkheil
- Department of Anatomical Sciences, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Mohammad Bayat
- Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
- Price Institute of Surgical Research, University of Louisville and Noveratech LLC of Louisville, Louisville, KY, USA.
| |
Collapse
|
28
|
Murohara T. Therapeutic Angiogenesis with Somatic Stem Cell Transplantation. Korean Circ J 2020; 50:12-21. [PMID: 31854154 PMCID: PMC6923231 DOI: 10.4070/kcj.2019.0288] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2019] [Accepted: 09/18/2019] [Indexed: 12/19/2022] Open
Abstract
Therapeutic angiogenesis is an important strategy to rescue ischemic tissues in patients with critical limb ischemia having no other treatment option such as endovascular angioplasty or bypass surgery. Studies indicated so far possibilities of therapeutic angiogenesis using autologous bone marrow mononuclear cells, CD34⁺ cells, peripheral blood mononuclear cells, adipose-derived stem/progenitor cells, and etc. Recent studies indicated that subcutaneous adipose tissue contains stem/progenitor cells that can give rise to several mesenchymal lineage cells. Moreover, these mesenchymal progenitor cells release a variety of angiogenic growth factors including vascular endothelial growth factor, fibroblast growth factor, hepatocyte growth factor and chemokine stromal cell-derived factor-1. Subcutaneous adipose tissues can be harvested by less invasive technique. These biological properties of adipose-derived regenerative cells (ADRCs) implicate that autologous subcutaneous adipose tissue would be a useful cell source for therapeutic angiogenesis in humans. In this review, I would like to discuss biological properties and future perspective of ADRCs-mediated therapeutic angiogenesis.
Collapse
Affiliation(s)
- Toyoaki Murohara
- Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
| |
Collapse
|
29
|
Emulsified Fat Grafting Accelerates Tissue Expansion: An Experimental Study in a Rat Model. Ann Plast Surg 2019; 85:61-67. [PMID: 31855863 DOI: 10.1097/sap.0000000000002137] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
INTRODUCTION Tissue expansion has been applied in tissue repair and reconstruction of large soft tissue defects. Stromal vascular fraction (SVF) transplantation is a promising treatment in raising expansion efficiency. However, the clinical utilization of SVF is limited because of its conventional collagenase-based production. The aim of this study was to evaluate the effect of emulsified fat (EF), SVF obtained by using mechanical method, on accelerating tissue expansion. MATERIALS AND METHODS The microstructure of EF fragments and the proportion of mesenchymal stem cells (MSCs; CD45-/CD34+) in EF were detected. Wistar rats were divided into the following 3 groups randomly: the 1-mL EF group, the 0.5-mL EF group, and the control group. The tissue expansion was carried out twice a week to maintain the capsule pressure at 60 mm Hg. After 4 weeks, inflation volume and histological changes, which includes collagen content, cell proliferation, and capillary density, were observed to evaluate the effect of EF on tissue expansion. RESULTS Mechanical emulsification effectively destroyed the mature adipocytes in adipose tissue. The proportion of MSCs population in the EF fragments was 12.40 ± 0.86%. After expansion, the inflation volume and the levels of collagen deposition, cell proliferation, and capillary density of the expanded tissue in the 1-mL EF group were significantly higher than that in the 0.5-mL EF group and the control group (P < 0.05). However, all these regenerative indicators in the 0.5-mL EF group showed no statistical difference from the control group (P > 0.05). The thickness of epidermal and dermal layers showed no significant difference among the 3 groups (P > 0.05). CONCLUSIONS Our findings suggested that EF grafting can be used as a new alternative to increase tissue expansion efficiency.
Collapse
|
30
|
Ni H, Zhao Y, Ji Y, Shen J, Xiang M, Xie Y. Adipose-derived stem cells contribute to cardiovascular remodeling. Aging (Albany NY) 2019; 11:11756-11769. [PMID: 31800397 PMCID: PMC6932876 DOI: 10.18632/aging.102491] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2019] [Accepted: 11/17/2019] [Indexed: 02/06/2023]
Abstract
Obesity is an independent risk factor for cardiovascular disease. Adipose tissue was initially thought to be involved in metabolism through paracrine. Recent researches discovered mesenchymal stem cells inside adipose tissue which could differentiate into vascular lineages in vitro and in vivo, participating vascular remodeling. However, there were few researches focusing on distinct characteristics and functions of adipose-derived stem cells (ADSCs) from different regions. This is the first comprehensive review demonstrating the variances of ADSCs from the perspective of their origins.
Collapse
Affiliation(s)
- Hui Ni
- Department of Cardiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yiming Zhao
- Department of Endocrinology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yongli Ji
- Department of Cardiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jian Shen
- Department of Cardiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Meixiang Xiang
- Department of Cardiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yao Xie
- Department of Cardiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| |
Collapse
|
31
|
Tran TDX, Wu CM, Dubey NK, Deng YH, Su CW, Pham TT, Thi Le PB, Sestili P, Deng WP. Time- and Kellgren⁻Lawrence Grade-Dependent Changes in Intra-Articularly Transplanted Stromal Vascular Fraction in Osteoarthritic Patients. Cells 2019; 8:E308. [PMID: 30987218 PMCID: PMC6523621 DOI: 10.3390/cells8040308] [Citation(s) in RCA: 39] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2019] [Revised: 03/29/2019] [Accepted: 04/01/2019] [Indexed: 12/13/2022] Open
Abstract
Knee osteoarthritis (OA) is one of the most prevalent disorders in elderly population. Among various therapeutic alternatives, we employed stromal vascular fraction (SVF), a heterogeneous cell population, to regenerate damaged knee cartilage. OA patients were classified on the basis of age, gender, body mass index (BMI), and x-ray-derived Kellgren-Lawrence (KL) grade. They were treated with SVF and followed-up for 24 months. Visual analogue scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index were used to determine treatment efficacy. Cartilage healing was assessed using the MRI-based Outerbridge score (OS) and evaluation of bone marrow edema (BME) lesions, while a placebo group was used as a control. Time- and KL-dependent changes were also monitored. We observed a decreasing trend in VAS score and WOMAC index in the SVF-treated group up to 24 months, as compared with the placebo group. Besides, a significant increase and decrease in Lysholm and OS, respectively, were observed in the treatment group. Compared with the values before treatment, the greatly reduced WOMAC scores of KL3 than KL2 groups at 24 months, indicate more improvement in the KL3 group. Highly decreased BME in the treated group was also noted. In conclusion, the SVF therapy is effective in the recovery of OA patients of KL3 grade in 24 months.
Collapse
Affiliation(s)
- Tung Dang Xuan Tran
- School of Dentistry, Taipei Medical University, Taipei 11031, Taiwan.
- Van Hanh Stem Cells Unit, Van Hanh Hospital, Ho Chi Minh City 700000, Vietnam.
| | - Chi-Ming Wu
- Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei 11031, Taiwan.
| | - Navneet Kumar Dubey
- Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei 11031, Taiwan.
- Stem Cell Research Center, College of Oral Medicine, Taipei Medical University, Taipei 11031, Taiwan.
| | - Yue-Hua Deng
- Department of Life Science, Fu Jen Catholic University, New Taipei City 242, Taiwan.
| | - Chun-Wei Su
- Stem Cell Research Center, College of Oral Medicine, Taipei Medical University, Taipei 11031, Taiwan.
| | - Tu Thanh Pham
- Van Hanh Stem Cells Unit, Van Hanh Hospital, Ho Chi Minh City 700000, Vietnam.
| | - Phuong Bich Thi Le
- Department of Pulmonary Medicine, Vietnam Military Medical Academy, Ha Noi 12108, Vietnam.
| | - Piero Sestili
- Dipartimento di Scienze Biomolecolari, Università degli Studi di Urbino Carlo Bo Via "I Maggetti" 26, 61029 Urbino, Italy.
| | - Win-Ping Deng
- School of Dentistry, Taipei Medical University, Taipei 11031, Taiwan.
- Stem Cell Research Center, College of Oral Medicine, Taipei Medical University, Taipei 11031, Taiwan.
| |
Collapse
|
32
|
He Y, Yu X, Chen Z, Li L. Stromal vascular fraction cells plus sustained release VEGF/Ang-1-PLGA microspheres improve fat graft survival in mice. J Cell Physiol 2018; 234:6136-6146. [PMID: 30238985 DOI: 10.1002/jcp.27368] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2018] [Accepted: 08/16/2018] [Indexed: 01/17/2023]
Abstract
Autologous fat transplantation is increasingly applied in plastic and reconstructive surgery. Stromal vascular fraction cells (SVFs) combined with angiogenic factors, such as VEGF (vascular endothelial growth factor A) and Ang-1 (angiogenin-1), can improve angiogenesis, which is a critical factor for graft survival. However, direct transplant with such a mixture is insufficient owing to the short half-life of angiogenic factors. In this study, we evaluated whether a double sustained release system of VEGF/ANG-1-PLGA (poly (lactic-co-glycolic acid)) microspheres plus SVFs can improve angiogenesis and graft survival after autologous fat transplantation. VEGF/ANG-1-PLGA-sustained release microspheres were fabricated by a modified double emulsion-solvent evaporation technique. Human aspirated fat was mixed with SVF suspension plus VEGF/ANG-1 sustained release microspheres (Group C), SVF suspension (Group B) alone, or Dulbecco's modified Eagle's medium as the control (Group A). Eighteen immunocompromised nude mice were injected with these three mixtures subcutaneously at random positions. After 8 weeks, the mean volume of grafts was greater in the SVFs plus VEGF/ANG-1-PLGA group than in the control and SVFs groups (1.08 ± 0.069 ml vs. 0.62 ± 0.036 ml, and 0.83 ± 0.059 ml, respectively). Histological assessments showed that lower fibrosis, but greater microvascular density in the SVFs plus VEGF/ANG-1-PLGA group than in the other groups, though the SVFs group also had an appropriate capillary density and reduced fibrosis. Our findings indicate that SVFs plus VEGF/ANG-1-PLGA-sustained release microspheres can improve angiogenesis and graft survival after autologous fat transplantation.
Collapse
Affiliation(s)
- Yucang He
- First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Xiaofang Yu
- First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Zhuojie Chen
- First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Liqun Li
- First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| |
Collapse
|
33
|
Shi N, Guo S, Su Y, Zhang Z, Qiu L, Yu Z, Yang Q, Wang N, Yi C. Improvement in the Retention Rate of Transplanted Fat in Muscle by Denervation. Aesthet Surg J 2018; 38:1026-1034. [PMID: 29992230 DOI: 10.1093/asj/sjy104] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Improvement in the retention rate of transplanted fat is currently a topic of interest. The retention of transplanted fat relies heavily on the reestablishment of blood supply and the function of the adipose-derived stem cells (ADSCs), which may both be impeded by mechanical force. However, the effect of mechanical force on the retention of adipose implants remains unclear. OBJECTIVES This study aimed to evaluate the effectiveness of immobilization on fat retention rate. METHODS Immobilization was carried out by denervation of the hind limb of rats to reduce the mechanical force. Sprague-Dawley (SD) rats were used, and the two hind limbs were assigned at random to the immobilization side and the control side. On average, 0.4 mL of fat was injected into the bilateral muscle and subcutaneous space of the hind limb, and 6 rats were sacrificed at each time point. The outcome measures included the retention rate, the histologic evaluation, and the density of new vessels and proliferative ADSCs. RESULTS For the muscle fat, the retention rate improved, and more proliferative ADSCs and new vessels were found in the immobilization group. The histologic evaluation between the two sides was of no statistical significance. For the fat in the subcutaneous space, no statistical difference was observed in all the outcome measures between the two sides. CONCLUSIONS Regional immobilization of the recipient site by denervation can improve the retention of the fat graft in muscles owing to improved density of the new vessels and proliferative ADSCs.
Collapse
Affiliation(s)
- Nian Shi
- Department of Plastic and Reconstructive Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, Shanxi, China
| | - Shuzhong Guo
- Department of Plastic and Reconstructive Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, Shanxi, China
| | - Yingjun Su
- Department of Plastic and Reconstructive Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, Shanxi, China
| | - Zhaoxiang Zhang
- Department of Plastic and Reconstructive Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, Shanxi, China
| | - Lihong Qiu
- Department of Plastic and Reconstructive Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, Shanxi, China
| | - Zhou Yu
- Department of Plastic and Reconstructive Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, Shanxi, China
| | - Qing Yang
- Department of Plastic and Reconstructive Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, Shanxi, China
| | - Na Wang
- Department of Plastic and Reconstructive Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, Shanxi, China
| | - Chenggang Yi
- Department of Plastic and Reconstructive Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, Shanxi, China
| |
Collapse
|
34
|
Haney NM, Gabrielson A, Kohn TP, Hellstrom WJG. The Use of Stromal Vascular Fraction in the Treatment of Male Sexual Dysfunction: A Review of Preclinical and Clinical Studies. Sex Med Rev 2018; 7:313-320. [PMID: 29960873 DOI: 10.1016/j.sxmr.2018.04.001] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2018] [Revised: 04/09/2018] [Accepted: 04/09/2018] [Indexed: 12/30/2022]
Abstract
INTRODUCTION Stem cell therapy using stromal vascular fraction (SVF) is a promising treatment modality. SVF is comprised of a mixture of adipose-derived stem cells, endothelial precursor cells, and immune modulatory cells that act synergistically to facilitate angiogenesis and epithelial cell differentiation. This makes SVF an attractive option for men's sexual disorders that require reconstitution of vasculature and endothelial lining, namely erectile dysfunction (ED) and Peyronie's disease (PD). AIM The objective of this study was to compare and contrast the available literature regarding the use of SVF in the treatment of male sexual dysfunction. METHODS A literature review was performed in PubMed with the keywords "stromal vascular fraction" and/or "erectile dysfunction" and/or "Peyronie's disease" and/or "sexual dysfunction." MAIN OUTCOME MEASURES The main outcome measure for preclinical studies was erectile function, as measured by changes in intracavernous pressures, and results of histopathologic analysis of corporal tissue. Clinical endpoint analysis in humans included various patient questionnaires. RESULTS For ED, there were 5 preclinical studies included in the analysis, with 1 Phase 1 clinical trial in humans. Major limitations of both the preclinical and clinical studies included the absence of SVF component analysis, and short duration of follow-up. Despite a paucity of preclinical studies, there was a single clinical study assessing the efficacy of combination SVF and shock wave therapy in the treatment of PD. Limitations of this study included an absence of a control group and the use of subjective data. CONCLUSION Preclinical and clinical data in the use of SVF for the treatment of male sexual dysfunction is deficient. Even though multiple medicinal disciplines are studying the use of SVF on a myriad of pathologies, further investigative work elucidating the mechanism and potential adverse effects of SVF need to be performed before clinical trials are undertaken. Haney NM, Gabrielson A, Kohn TP, Hellstrom WJG. The Use of Stromal Vascular Fraction in the Treatment of Male Sexual Dysfunction: A Review of Preclinical and Clinical Studies. Sex Med Rev 2019;7:313-320.
Collapse
Affiliation(s)
- Nora M Haney
- Tulane University School of Medicine, Department of Urology, New Orleans, LA, USA
| | - Andrew Gabrielson
- Tulane University School of Medicine, Department of Urology, New Orleans, LA, USA
| | - Taylor P Kohn
- Baylor College of Medicine, Department of Urology, Houston, TX, USA
| | - Wayne J G Hellstrom
- Tulane University School of Medicine, Department of Urology, New Orleans, LA, USA.
| |
Collapse
|
35
|
Cerino G, Gaudiello E, Muraro MG, Eckstein F, Martin I, Scherberich A, Marsano A. Engineering of an angiogenic niche by perfusion culture of adipose-derived stromal vascular fraction cells. Sci Rep 2017; 7:14252. [PMID: 29079730 PMCID: PMC5660248 DOI: 10.1038/s41598-017-13882-3] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2017] [Accepted: 10/02/2017] [Indexed: 01/01/2023] Open
Abstract
In vitro recapitulation of an organotypic stromal environment, enabling efficient angiogenesis, is crucial to investigate and possibly improve vascularization in regenerative medicine. Our study aims at engineering the complexity of a vascular milieu including multiple cell-types, a stromal extracellular matrix (ECM), and molecular signals. For this purpose, the human adipose stromal vascular fraction (SVF), composed of a heterogeneous mix of pericytes, endothelial/stromal progenitor cells, was cultured under direct perfusion flow on three-dimensional (3D) collagen scaffolds. Perfusion culture of SVF-cells reproducibly promoted in vitro the early formation of a capillary-like network, embedded within an ECM backbone, and the release of numerous pro-angiogenic factors. Compared to static cultures, perfusion-based engineered constructs were more rapidly vascularized and supported a superior survival of delivered cells upon in vivo ectopic implantation. This was likely mediated by pericytes, whose number was significantly higher (4.5-fold) under perfusion and whose targeted depletion resulted in lower efficiency of vascularization, with an increased host foreign body reaction. 3D-perfusion culture of SVF-cells leads to the engineering of a specialized milieu, here defined as an angiogenic niche. This system could serve as a model to investigate multi-cellular interactions in angiogenesis, and as a module supporting increased grafted cell survival in regenerative medicine.
Collapse
Affiliation(s)
- Giulia Cerino
- Departments of Biomedicine and Surgery, University of Basel and University Hospital of Basel, 4031, Basel, Switzerland
| | - Emanuele Gaudiello
- Departments of Biomedicine and Surgery, University of Basel and University Hospital of Basel, 4031, Basel, Switzerland
| | - Manuele Giuseppe Muraro
- Departments of Biomedicine and Surgery, University of Basel and University Hospital of Basel, 4031, Basel, Switzerland
| | - Friedrich Eckstein
- Departments of Biomedicine and Surgery, University of Basel and University Hospital of Basel, 4031, Basel, Switzerland
| | - Ivan Martin
- Departments of Biomedicine and Surgery, University of Basel and University Hospital of Basel, 4031, Basel, Switzerland
| | - Arnaud Scherberich
- Departments of Biomedicine and Surgery, University of Basel and University Hospital of Basel, 4031, Basel, Switzerland
| | - Anna Marsano
- Departments of Biomedicine and Surgery, University of Basel and University Hospital of Basel, 4031, Basel, Switzerland.
| |
Collapse
|
36
|
Fujita Y, Kawamoto A. Stem cell-based peripheral vascular regeneration. Adv Drug Deliv Rev 2017; 120:25-40. [PMID: 28912015 DOI: 10.1016/j.addr.2017.09.001] [Citation(s) in RCA: 56] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2017] [Revised: 08/28/2017] [Accepted: 09/07/2017] [Indexed: 02/07/2023]
Abstract
Chronic critical limb ischemia (CLI) represents an end-stage manifestation of peripheral arterial disease (PAD). CLI patients are at very high risk of amputation and cardiovascular complications, leading to severe morbidity and mortality. Because many patients with CLI are ineligible for conventional revascularization procedures, it is urgently needed to explore alternative strategies to improve blood supply in the ischemic tissue. Although researchers initially focused on gene/protein therapy using proangiogenic growth factors/cytokines, recent discovery of somatic stem/progenitor cells including bone marrow (BM)-derived endothelial progenitor cells (EPCs) and mesenchymal stem cells (MSCs) has drastically developed the field of therapeutic angiogenesis for CLI. Overall, early phase clinical trials demonstrated that stem/progenitor cell therapies may be safe, feasible and potentially effective. However, only few late-phase clinical trials have been conducted. This review provides an overview of the preclinical and clinical reports to demonstrate the usefulness and the current limitations of the cell-based therapies.
Collapse
Affiliation(s)
- Yasuyuki Fujita
- Division of Vascular Regeneration, Unit of Regenerative Medicine, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation, Japan; Translational Research Informatics Center, Foundation for Biomedical Research and Innovation, Japan
| | - Atsuhiko Kawamoto
- Division of Vascular Regeneration, Unit of Regenerative Medicine, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation, Japan; Translational Research Informatics Center, Foundation for Biomedical Research and Innovation, Japan.
| |
Collapse
|
37
|
Carstens MH, Mendieta M, Pérez C, Villareal E, Garcia R. Assisted Salvage of Ischemic Fasciocutaneous Flap Using Adipose-Derived Mesenchymal Stem Cells: In-Situ Revascularization. Aesthet Surg J 2017; 37:S38-S45. [PMID: 29025216 PMCID: PMC5846702 DOI: 10.1093/asj/sjx052] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023] Open
Abstract
Adipose-derived mesenchymal stem cells (ASCs) have been shown to produce vascular endothelial growth factor (VEGF) and can increase perfusion in patients with critical limb ischemia. We will show that this concept can be applied to augment blood flow in zones of flap ischemia. We presented a case study of a 26-year-old man with a complex hand injury covered by a reverse radial perforator fasciocutaneous flap, which developed ischemic necrosis and was treated by debridement, transplantation of ASCs to enhance vascular support, and saline dressings. ASCs are found in the stromal vascular fraction (SVF), a heterogeneous collection of cells, including pericytes and endothelial cells, that is prepared from lipoaspirate using collagenase digestion followed by centrifugation. These were injected into the flap, the palmar tissues both subjacent and peripheral to the flap, and the skin-grafted donor site. The case was documented with photography, measurements at hand therapy, and follow-up angiography MRI. At 72 hours, new vessels appeared diffusely; at 1 week, the remaining tissues of flap were bleeding. The wound, 11 cm × 4 cm, contracted spontaneously and was healed at 21 days. The skin graft over the donor site demonstrated unusual suppleness and elasticity. 3D CT angiography disclosed a new layer of vascularity in the superficial tissues of the palm when compared with the normal side. The patient regained full composite flexion, pinch, opposition, and wrist extension. Application of ASCs into the supporting tissues surrounding the ischemic flap, and into the flap itself, constituted a form of in-situ revascularization (ISR) that was subjectively and objectively effective for this patient. LEVEL OF EVIDENCE 5.
Collapse
Affiliation(s)
- Michael H Carstens
- Dr Carstens is a Clinical Associate Professor of Plastic Surgery, Saint Louis University, St. Louis, MO; and a Professor of Plastic Surgery, National University of Nicaragua in Leon, Nicaragua. Dr Mendieta is a plastic surgeon in private practice in Managua, Nicaragua. Dr Pérez is a radiologist in private practice in Managua, Nicaragua. Dr Villareal is a physiatrist in private practice in Managua, Nicaragua. Mr Garcia is a physical therapist in private practice in Managua, Nicaragua
| | - Mauricio Mendieta
- Dr Carstens is a Clinical Associate Professor of Plastic Surgery, Saint Louis University, St. Louis, MO; and a Professor of Plastic Surgery, National University of Nicaragua in Leon, Nicaragua. Dr Mendieta is a plastic surgeon in private practice in Managua, Nicaragua. Dr Pérez is a radiologist in private practice in Managua, Nicaragua. Dr Villareal is a physiatrist in private practice in Managua, Nicaragua. Mr Garcia is a physical therapist in private practice in Managua, Nicaragua
| | - Cecilia Pérez
- Dr Carstens is a Clinical Associate Professor of Plastic Surgery, Saint Louis University, St. Louis, MO; and a Professor of Plastic Surgery, National University of Nicaragua in Leon, Nicaragua. Dr Mendieta is a plastic surgeon in private practice in Managua, Nicaragua. Dr Pérez is a radiologist in private practice in Managua, Nicaragua. Dr Villareal is a physiatrist in private practice in Managua, Nicaragua. Mr Garcia is a physical therapist in private practice in Managua, Nicaragua
| | - Esperanza Villareal
- Dr Carstens is a Clinical Associate Professor of Plastic Surgery, Saint Louis University, St. Louis, MO; and a Professor of Plastic Surgery, National University of Nicaragua in Leon, Nicaragua. Dr Mendieta is a plastic surgeon in private practice in Managua, Nicaragua. Dr Pérez is a radiologist in private practice in Managua, Nicaragua. Dr Villareal is a physiatrist in private practice in Managua, Nicaragua. Mr Garcia is a physical therapist in private practice in Managua, Nicaragua
| | - Rodolfo Garcia
- Dr Carstens is a Clinical Associate Professor of Plastic Surgery, Saint Louis University, St. Louis, MO; and a Professor of Plastic Surgery, National University of Nicaragua in Leon, Nicaragua. Dr Mendieta is a plastic surgeon in private practice in Managua, Nicaragua. Dr Pérez is a radiologist in private practice in Managua, Nicaragua. Dr Villareal is a physiatrist in private practice in Managua, Nicaragua. Mr Garcia is a physical therapist in private practice in Managua, Nicaragua
| |
Collapse
|
38
|
Costa M, Cerqueira MT, Santos TC, Sampaio-Marques B, Ludovico P, Marques AP, Pirraco RP, Reis RL. Cell sheet engineering using the stromal vascular fraction of adipose tissue as a vascularization strategy. Acta Biomater 2017; 55:131-143. [PMID: 28347862 DOI: 10.1016/j.actbio.2017.03.034] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2017] [Revised: 03/20/2017] [Accepted: 03/23/2017] [Indexed: 12/17/2022]
Abstract
Current vascularization strategies for Tissue Engineering constructs, in particular cell sheet-based, are limited by time-consuming and expensive endothelial cell isolation and/or by the complexity of using extrinsic growth factors. Herein, we propose an alternative strategy using angiogenic cell sheets (CS) obtained from the stromal vascular fraction (SVF) of adipose tissue that can be incorporated into more complex constructs. Cells from the SVF were cultured in normoxic and hypoxic conditions for up to 8days in the absence of extrinsic growth factors. Immunocytochemistry against CD31 and CD146 revealed spontaneous organization in capillary-like structures, more complex after hypoxic conditioning. Inhibition of HIF-1α pathway hindered capillary-like structure formation in SVF cells cultured in hypoxia, suggesting a role of HIF-1α. Moreover, hypoxic SVF cells showed a trend for increased secretion of angiogenic factors, which was reflected in increased network formation by endothelial cells cultured on matrigel using that conditioned medium. In vivo implantation of SVF CS in a mouse hind limb ischemia model revealed that hypoxia-conditioned CS led to improved restoration of blood flow. Both in vitro and in vivo data suggest that SVF CS can be used as simple and cost-efficient tools to promote functional vascularization of TE constructs. STATEMENT OF SIGNIFICANCE Neovascularization after implantation is a major obstacle for producing clinically viable cell sheet-based tissue engineered constructs. Strategies using endothelial cells and extrinsic angiogenic growth factors are expensive and time consuming and may raise concerns of tumorigenicity. In this manuscript, we describe a simplified approach using angiogenic cell sheets fabricated from the stromal vascular fraction of adipose tissue. The strong angiogenic behavior of these cell sheets, achieved without the use of external growth factors, was further stimulated by low oxygen culture. When implanted in an in vivo model of hind limb ischemia, the angiogenic cell sheets contributed to blood flux recovery. These cell sheets can therefore be used as a straightforward tool to increase the neovascularization of cell sheet-based thick constructs.
Collapse
Affiliation(s)
- Marina Costa
- 3B's Research Group - Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, 4805-017 Barco, Guimarães, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal; Institute of Biophysics and Biomedical Engineering, Faculty of Sciences of the University of Lisbon, Lisbon, Portugal
| | - Mariana T Cerqueira
- 3B's Research Group - Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, 4805-017 Barco, Guimarães, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - Tírcia C Santos
- 3B's Research Group - Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, 4805-017 Barco, Guimarães, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - Belém Sampaio-Marques
- Institute of Life and Health Sciences, School of Medicine, University of Minho, Braga, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - Paula Ludovico
- Institute of Life and Health Sciences, School of Medicine, University of Minho, Braga, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - Alexandra P Marques
- 3B's Research Group - Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, 4805-017 Barco, Guimarães, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - Rogério P Pirraco
- 3B's Research Group - Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, 4805-017 Barco, Guimarães, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - Rui L Reis
- 3B's Research Group - Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, 4805-017 Barco, Guimarães, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
| |
Collapse
|
39
|
Ito S, Kai Y, Masuda T, Tanaka F, Matsumoto T, Kamohara Y, Hayakawa H, Ueo H, Iwaguro H, Hedrick MH, Mimori K, Mori M. Long-term outcome of adipose-derived regenerative cell-enriched autologous fat transplantation for reconstruction after breast-conserving surgery for Japanese women with breast cancer. Surg Today 2017; 47:1500-1511. [PMID: 28555267 DOI: 10.1007/s00595-017-1544-4] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2017] [Accepted: 05/02/2017] [Indexed: 12/17/2022]
Abstract
PURPOSE More effective methods are needed for breast reconstruction after breast-conserving surgery for breast cancer. The aim of this clinical study was to assess the perioperative and long-term outcomes of adipose-derived regenerative cell (ADRC)-enriched autologous fat grafting. METHODS Ten female patients who had undergone breast-conserving surgery and adjuvant radiotherapy for breast cancer were enrolled. An ADRC-enriched fat graft prepared from the patient's adipose tissue was implanted at the time of adipose tissue harvest. The perioperative and long-term outcomes of the grafts, which included safety, efficacy, and questionnaire-based patient satisfaction, were investigated. RESULTS The mean operation time was 188 ± 30 min, and the mean duration of postoperative hospitalization was 1.2 ± 0.4 days. No serious postoperative complications were associated with the procedure. Neither recurrence nor metastatic disease was observed during the follow-up period (7.8 ± 1.5 years) after transplantation. Of 9 available patients, "more than or equal to average" satisfaction with breast appearance and overall satisfaction were reported by 6 (66.7%) and 5 (55.6%) patients, respectively. CONCLUSIONS ADRC-enriched autologous fat transplantation is thus considered to be safe perioperatively, with no long-term recurrence, for patients with breast cancer treated by breast-conserving surgery, and it may be an option for breast reconstruction, even after adjuvant radiotherapy.
Collapse
Affiliation(s)
- Shuhei Ito
- Department of Surgery, Kyushu University Beppu Hospital, 4546 Tsurumihara, Beppu, 874-0838, Japan
| | - Yuichiro Kai
- Department of Surgery, Kyushu University Beppu Hospital, 4546 Tsurumihara, Beppu, 874-0838, Japan.,Ueo Breast Surgical Hospital, Oita, Japan
| | - Takaaki Masuda
- Department of Surgery, Kyushu University Beppu Hospital, 4546 Tsurumihara, Beppu, 874-0838, Japan
| | - Fumiaki Tanaka
- Department of Surgery, Kyushu University Beppu Hospital, 4546 Tsurumihara, Beppu, 874-0838, Japan
| | - Toshifumi Matsumoto
- Department of Surgery, Kyushu University Beppu Hospital, 4546 Tsurumihara, Beppu, 874-0838, Japan
| | - Yukio Kamohara
- Department of Surgery, Kyushu University Beppu Hospital, 4546 Tsurumihara, Beppu, 874-0838, Japan
| | | | | | | | | | - Koshi Mimori
- Department of Surgery, Kyushu University Beppu Hospital, 4546 Tsurumihara, Beppu, 874-0838, Japan.
| | - Masaki Mori
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Japan
| |
Collapse
|
40
|
Im GI. Bone marrow-derived stem/stromal cells and adipose tissue-derived stem/stromal cells: Their comparative efficacies and synergistic effects. J Biomed Mater Res A 2017; 105:2640-2648. [PMID: 28419760 DOI: 10.1002/jbm.a.36089] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2017] [Revised: 03/13/2017] [Accepted: 04/11/2017] [Indexed: 12/20/2022]
Abstract
Mesenchymal stem cells (MSCs) are heterogeneous cell populations that serve as reserves for tissue regeneration in the presence of disease or injury. Although MSCs are found in various tissues, bone marrow-derived stem/stromal cells (BMSCs) and adipose tissue-derived stem/stromal cells (ADSCs) have been most thoroughly investigated. Furthermore, ADSCs have recently emerged as an attractive source of MSCs due to their abundance and availability. BMSCs and ADSCs demonstrate similar morphological characteristics, but their in vitro characteristics and differentiation abilities appear to differ. In this review, the author summarizes and compares current knowledge on BMSCs and ADSCs with particular emphasis on in vitro expansion and osteogenic/angiogenic potential, and reviews knowledge of their synergistic effects when co-applied. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2640-2648, 2017.
Collapse
Affiliation(s)
- Gun-Il Im
- Department of Orthopaedics, Dongguk University Ilsan Hospital, Goyang, Republic of Korea
| |
Collapse
|
41
|
Skin Tissue Engineering: Application of Adipose-Derived Stem Cells. BIOMED RESEARCH INTERNATIONAL 2017; 2017:9747010. [PMID: 28337463 PMCID: PMC5350314 DOI: 10.1155/2017/9747010] [Citation(s) in RCA: 69] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/14/2016] [Revised: 10/23/2016] [Accepted: 10/30/2016] [Indexed: 02/06/2023]
Abstract
Perception of the adipose tissue has changed dramatically over the last few decades. Identification of adipose-derived stem cells (ASCs) ultimately transformed paradigm of this tissue from a passive energy depot into a promising stem cell source with properties of self-renewal and multipotential differentiation. As compared to bone marrow-derived stem cells (BMSCs), ASCs are more easily accessible and their isolation yields higher amount of stem cells. Therefore, the ASCs are of high interest for stem cell-based therapies and skin tissue engineering. Currently, freshly isolated stromal vascular fraction (SVF), which may be used directly without any expansion, was also assessed to be highly effective in treating skin radiation injuries, burns, or nonhealing wounds such as diabetic ulcers. In this paper, we review the characteristics of SVF and ASCs and the efficacy of their treatment for skin injuries and disorders.
Collapse
|
42
|
Jin E, Chae DS, Son M, Kim SW. Angiogenic characteristics of human stromal vascular fraction in ischemic hindlimb. Int J Cardiol 2017; 234:38-47. [PMID: 28258850 DOI: 10.1016/j.ijcard.2017.02.080] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2016] [Revised: 02/03/2017] [Accepted: 02/20/2017] [Indexed: 10/20/2022]
Abstract
INTRODUCTION In this study, we sought to characterize the angio-vasculogenic property of human adipose tissue-derived stromal vascular fraction (SVF) and to determine the therapeutic potential of SVF in the context of experimental ischemia. Although human SVF is used for cell therapy, its angiogenic and vasculogenic characteristics have not been fully elucidated. METHODS AND RESULTS We conducted flow cytometry, microarray, quantitative (q)-PCR, Matrigel tube formation assays and in vivo therapeutic assays using an ischemic hind limb mouse model. Gene/micro RNA microarray, quantitative (q)-PCR results revealed that the representative pro-angiogenic factors were highly upregulated in SVF compared with human adipose-derived mesenchymal stem cells (ASCs). In addition, SVF exhibited high expression of endothelium-specific genes and showed robust in vitro micro-vascular formation. SVF was transplanted into ischemic mouse hind limbs and compared with ASC transplantation. SVF transplantation prevented limb loss and augmented blood perfusion, indicating that SVF promotes neovascularization in hind limb ischemia. Transplanted SVF showed high vasculogenic potential in vivo compared with transplanted ASCs. CONCLUSIONS Our data indicate that SVF has remarkable therapeutic effects on hind limb ischemia via robust angiogenic and vasculogenic activity.
Collapse
Affiliation(s)
- Enze Jin
- Department of Cardiology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Dong-Sik Chae
- Department of Orthopedic Surgery, International St. Mary's Hospital, Catholic Kwandong University College of Medicine, Incheon, Republic of Korea
| | - Mina Son
- Department of Medicine, College of Medicine, Catholic Kwandong University, Gangneung, Republic of Korea
| | - Sung-Whan Kim
- Department of Medicine, College of Medicine, Catholic Kwandong University, Gangneung, Republic of Korea.
| |
Collapse
|
43
|
Carstens MH, Gómez A, Cortés R, Turner E, Pérez C, Ocon M, Correa D. Non-reconstructable peripheral vascular disease of the lower extremity in ten patients treated with adipose-derived stromal vascular fraction cells. Stem Cell Res 2017; 18:14-21. [DOI: 10.1016/j.scr.2016.12.001] [Citation(s) in RCA: 42] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2016] [Revised: 11/04/2016] [Accepted: 12/02/2016] [Indexed: 12/22/2022] Open
|
44
|
Rotondo F, Romero MDM, Ho-Palma AC, Remesar X, Fernández-López JA, Alemany M. Quantitative analysis of rat adipose tissue cell recovery, and non-fat cell volume, in primary cell cultures. PeerJ 2016; 4:e2725. [PMID: 27917316 PMCID: PMC5131620 DOI: 10.7717/peerj.2725] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2016] [Accepted: 10/26/2016] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND White adipose tissue (WAT) is a complex, diffuse, multifunctional organ which contains adipocytes, and a large proportion of fat, but also other cell types, active in defense, regeneration and signalling functions. Studies with adipocytes often require their isolation from WAT by breaking up the matrix of collagen fibres; however, it is unclear to what extent adipocyte number in primary cultures correlates with their number in intact WAT, since recovery and viability are often unknown. EXPERIMENTAL DESIGN Epididymal WAT of four young adult rats was used to isolate adipocytes with collagenase. Careful recording of lipid content of tissue, and all fraction volumes and weights, allowed us to trace the amount of initial WAT fat remaining in the cell preparation. Functionality was estimated by incubation with glucose and measurement of glucose uptake and lactate, glycerol and NEFA excretion rates up to 48 h. Non-adipocyte cells were also recovered and their sizes (and those of adipocytes) were measured. The presence of non-nucleated cells (erythrocytes) was also estimated. RESULTS Cell numbers and sizes were correlated from all fractions to intact WAT. Tracing the lipid content, the recovery of adipocytes in the final, metabolically active, preparation was in the range of 70-75%. Cells showed even higher metabolic activity in the second than in the first day of incubation. Adipocytes were 7%, erythrocytes 66% and other stromal (nucleated cells) 27% of total WAT cells. However, their overall volumes were 90%, 0.05%, and 0.2% of WAT. Non-fat volume of adipocytes was 1.3% of WAT. CONCLUSIONS The methodology presented here allows for a direct quantitative reference to the original tissue of studies using isolated cells. We have also found that the "live cell mass" of adipose tissue is very small: about 13 µL/g for adipocytes and 2 µL/g stromal, plus about 1 µL/g blood (the rats were killed by exsanguination). These data translate (with respect to the actual "live cytoplasm" size) into an extremely high metabolic activity, which make WAT an even more significant agent in the control of energy metabolism.
Collapse
Affiliation(s)
- Floriana Rotondo
- Department of Biochemistry and Molecular Biomedicine, Faculty of Biology, University of Barcelona, Barcelona, Spain
- Institute of Biomedicine, University of Barcelona, Barcelona, Spain
| | - María del Mar Romero
- Department of Biochemistry and Molecular Biomedicine, Faculty of Biology, University of Barcelona, Barcelona, Spain
- Institute of Biomedicine, University of Barcelona, Barcelona, Spain
- CIBER OBN, Barcelona, Spain
| | - Ana Cecilia Ho-Palma
- Department of Biochemistry and Molecular Biomedicine, Faculty of Biology, University of Barcelona, Barcelona, Spain
| | - Xavier Remesar
- Department of Biochemistry and Molecular Biomedicine, Faculty of Biology, University of Barcelona, Barcelona, Spain
- Institute of Biomedicine, University of Barcelona, Barcelona, Spain
- CIBER OBN, Barcelona, Spain
| | - José Antonio Fernández-López
- Department of Biochemistry and Molecular Biomedicine, Faculty of Biology, University of Barcelona, Barcelona, Spain
- Institute of Biomedicine, University of Barcelona, Barcelona, Spain
- CIBER OBN, Barcelona, Spain
| | - Marià Alemany
- Department of Biochemistry and Molecular Biomedicine, Faculty of Biology, University of Barcelona, Barcelona, Spain
- Institute of Biomedicine, University of Barcelona, Barcelona, Spain
- CIBER OBN, Barcelona, Spain
| |
Collapse
|
45
|
Khan S, Villalobos MA, Choron RL, Chang S, Brown SA, Carpenter JP, Tulenko TN, Zhang P. Fibroblast growth factor and vascular endothelial growth factor play a critical role in endotheliogenesis from human adipose-derived stem cells. J Vasc Surg 2016; 65:1483-1492. [PMID: 27514438 DOI: 10.1016/j.jvs.2016.04.034] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2015] [Accepted: 04/08/2016] [Indexed: 01/22/2023]
Abstract
OBJECTIVE Adipose-derived stem cells (ASCs) are a potential adult mesenchymal stem cell source for restoring endothelial function in patients with critical limb ischemia. Fibroblast growth factor 2 (FGF2) and vascular endothelial growth factor (VEGF) play a major role in angiogenesis and wound healing. This study evaluated the effects of FGF and VEGF on the proliferation, migration, and potential endothelial differentiation of human ASCs with regards to their use as endothelial cell substitutes. METHODS ASCs were isolated from clinical lipoaspirates and cultured in M199 medium with fetal bovine serum (10%), FGF2 (10 ng/mL), VEGF (50 ng/mL), or combinations of FGF2 and VEGF. Cell proliferation rates, viability, and migration were measured by growth curves, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), and scratch assays. For cell attachment determinations, ASCs were seeded onto a scaffold of small intestinal submucosa for 5 days. Endothelial differentiation capabilities of ASCs were confirmed by expression of endothelial cell-specific markers using quantitative polymerase chain reaction, immunofluorescence staining, and cord formation on Matrigel (BD Biosciences, San Jose, Calif). PD173074, a selective inhibitor of FGF receptor, was used to confirm the importance of FGF signaling. RESULTS ASCs treated with FGF or combinations of FGF and VEGF showed increased proliferation rates and consistent differentiation toward an endothelial cell lineage increase in platelet endothelial cell adhesion molecule (CD31), von Willebrand factor, endothelial nitric oxide synthase, and vascular endothelial cadherin message, and in protein and cord formation on Matrigel. FGF and VEGF stimulated ASC migration and increased the attachment and retention after seeding onto a matrix graft of small intestinal submucosa. Blockade of FGF signaling with PD173074 abrogated ASC endothelial cell differentiation potential. CONCLUSIONS These results indicate that FGF and VEGF are ASC promoters for proliferation, migration, attachment, and endothelial differentiation. FGF and VEGF have a costimulatory effect on ASC endotheliogenesis. These results further suggest that ASCs with enhanced FGF signaling may potentially be used for tissue engineering and cell-based therapies in patients with critical limb ischemia.
Collapse
Affiliation(s)
- Sophia Khan
- Department of Surgery, Cooper University Hospital and Cooper Medical School of Rowan University, Camden, NJ
| | - Miguel A Villalobos
- Department of Surgery, Cooper University Hospital and Cooper Medical School of Rowan University, Camden, NJ
| | - Rachel L Choron
- Department of Surgery, Cooper University Hospital and Cooper Medical School of Rowan University, Camden, NJ
| | - Shaohua Chang
- Department of Surgery, Cooper University Hospital and Cooper Medical School of Rowan University, Camden, NJ
| | - Spencer A Brown
- Department of Surgery, Cooper University Hospital and Cooper Medical School of Rowan University, Camden, NJ
| | - Jeffrey P Carpenter
- Department of Surgery, Cooper University Hospital and Cooper Medical School of Rowan University, Camden, NJ
| | - Thomas N Tulenko
- Department of Surgery, Cooper University Hospital and Cooper Medical School of Rowan University, Camden, NJ
| | - Ping Zhang
- Department of Surgery, Cooper University Hospital and Cooper Medical School of Rowan University, Camden, NJ.
| |
Collapse
|
46
|
Kim M, Kim DI, Kim EK, Kim CW. CXCR4 Overexpression in Human Adipose Tissue-Derived Stem Cells Improves Homing and Engraftment in an Animal Limb Ischemia Model. Cell Transplant 2016; 26:191-204. [PMID: 27501830 DOI: 10.3727/096368916x692708] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
We investigated the effects of transplantation of CXCR4-overexpressing adipose tissue-derived stem cells (ADSCs) into a mouse diabetic hindlimb ischemia model on homing and engraftment as early as 48 h after transplant. CXCR4-overexpressing ADSCs were intramuscularly or intravenously injected into diabetic mice with hindlimb ischemia. After 48 h, muscle tissues in the femur and tibia were collected, and the CXCR4 expression pattern was analyzed by immunofluorescence staining. The homing and engraftment of transplanted CXCR4-overexpressing ADSCs into the ischemic area were significantly increased, and intravenous (systemic) injection resulted in the more effective delivery of stem cells to the target site 48 h posttransplantation. Furthermore, CXCR4-overexpressing ADSCs more efficiently contributed to long-term engraftment and muscle tissue regeneration than normal ADSCs in a limb ischemia model. In addition, the homing and engraftment of ADSCs were correlated with the CXCR4 transfection efficiency. These results demonstrated that enhanced CXCR4 signaling could significantly improve the early homing and engraftment of ADSCs into ischemic areas as well as the long-term engraftment and ultimate muscle tissue regeneration.
Collapse
|
47
|
Park IS, Chung PS, Ahn JC. Angiogenic Synergistic Effect of Adipose-Derived Stromal Cell Spheroids with Low-Level Light Therapy in a Model of Acute Skin Flap Ischemia. Cells Tissues Organs 2016; 202:307-318. [DOI: 10.1159/000445710] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/21/2016] [Indexed: 11/19/2022] Open
Abstract
Human adipose-derived mesenchymal stem cells (hASCs) are an attractive cell source for tissue engineering. However, one obstacle to this approach is that the transplanted hASC population can decline rapidly in the recipient tissue. The aim of this study was to investigate the effects of low-level light therapy (LLLT) on transplanted spheroid hASCs in skin flaps of mice. hASCs were cultured in monolayers or spheroids. LLLT, hASCs, spheroids and spheroids transplanted with LLLT were applied to the skin flaps. Healing of the skin flaps was assessed by gross evaluation and by hematoxylin and eosin staining and elastin van Gieson staining. Compared with the spheroid group, skin flap healing was enhanced in the spheroid + LLLT group, including the neovascularization and regeneration of skin appendages. The survival of hASCs was enhanced by decreased apoptosis of hASCs in the skin flaps of the spheroid + LLLT group. The secretion of growth factors was stimulated in the spheroid + LLLT group compared with the ASC and spheroid groups. These data suggest that LLLT was an effective biostimulator of spheroid hASCs in the skin flaps, enhancing the survival of hASCs and stimulating the secretion of growth factors.
Collapse
|
48
|
Van Pham P, Vu NB, Nguyen HT, Phan NK. Isolation of endothelial progenitor cells from human adipose tissue. BIOMEDICAL RESEARCH AND THERAPY 2016. [DOI: 10.7603/s40730-016-0024-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
|
49
|
Ataman MG, Uysal CA, Ertas NM, Bayraktar N, Terzi A, Borman H. The effect of adipose stromal vascular fraction on transverse rectus abdominis musculocutaneous flap: an experimental study. J Plast Surg Hand Surg 2016; 50:272-80. [PMID: 27010192 DOI: 10.3109/2000656x.2016.1159217] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND Transverse rectus abdominis musculocutaneous (TRAM) flap is one of the options in reconstruction after breast cancer surgery for breast reconstruction. Tissue necrosis often occurs in the third and fourth perfusion zones of the flap. A study was planned to find out the effects of adipose stromal vascular fraction (SVF) cells on viability of TRAM flap and the experimental model was designed to be applicable in clinical practice. METHODS Right inferior epigastric artery pedicled, 5 × 2.5 cm sized TRAM flap was used as a flap model in 30 rats in three groups (group 1: sham; group 2: phosphate-buffered saline (PBS); group 3: SVF cell injected). The viability of the flaps were assessed on the postoperative 7th day with photographs and software for the calculations. RESULTS The mean viable flap percentage to total flap area was recorded as 51.8% ± 11.19, 49.5% ± 10.30, 82.3% ± 9.56, in group 1, group 2, and group 3, respectively (p < 0.05). The mean capillary density was noted as 5.15 ± 0.56, 4.37 ± 0.58, and 12.40 ± 1.17 in groups 1, 2, and 3, respectively (p < 0.05). The fibrosis gradient indicated no difference between the groups (p > 0.05). The in-vivo differentiation of SVF cells to endothelial cells was noted. The blood VEGF levels showed a marked increase in the experimental group (p < 0.05). CONCLUSION The adipose SVF cells were found out to improve the TRAM flap viability and decrease necrosis, especially in zone 3 and 4.
Collapse
Affiliation(s)
- Murat Gorkem Ataman
- a Department of Plastic, Reconstructive Surgery , Baskent University Faculty of Medicine , Ankara , Turkey
| | - Cagri A Uysal
- a Department of Plastic, Reconstructive Surgery , Baskent University Faculty of Medicine , Ankara , Turkey
| | - Nilgun Markal Ertas
- a Department of Plastic, Reconstructive Surgery , Baskent University Faculty of Medicine , Ankara , Turkey
| | - Nilufer Bayraktar
- b Department of Biochemistry , Baskent University Faculty of Medicine , Ankara , Turkey
| | - Aysen Terzi
- c Department of Pathology , Baskent University Faculty of Medicine , Ankara , Turkey
| | - Huseyin Borman
- a Department of Plastic, Reconstructive Surgery , Baskent University Faculty of Medicine , Ankara , Turkey
| |
Collapse
|
50
|
Park IS, Mondal A, Chung PS, Ahn JC. Prevention of skin flap necrosis by use of adipose-derived stromal cells with light-emitting diode phototherapy. Cytotherapy 2016; 17:283-92. [PMID: 25659641 DOI: 10.1016/j.jcyt.2014.10.017] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2014] [Revised: 10/20/2014] [Accepted: 10/23/2014] [Indexed: 12/24/2022]
Abstract
BACKGROUND AIMS The aim of this study was to investigate the effects of low-level light therapy (LLLT) on transplanted human adipose-derived mesenchymal stromal cells (ASCs) in the skin flap of mice. METHODS LLLT, ASC transplantation and ASC transplantation with LLLT (ASC + LLLT) were applied to the skin flap. Immunostaining and Western blot analysis were performed to evaluate cell survival and differentiation and secretion of vascular endothelial growth factor and basic fibroblast growth factor by the ASCs. Vascular regeneration was assessed by means of immunostaining in addition to hematoxylin and eosin staining. In the ASC + LLLT group, the survival of ASCs was increased as the result of the decreased apoptosis of ASCs. RESULTS The secretion of growth factors was higher in this group as compared with ASCs alone. ASCs contributed to tissue regeneration through vascular cell differentiation and secretion of angiogenic growth factors. The ASC + LLLT group displayed improved treatment efficacy including neovascularization and tissue regeneration compared with ASCs alone. Transplanting ASCs to ischemic skin flaps improved therapeutic efficacy for ischemia treatment as the result of enhanced cell survival and paracrine effects. CONCLUSIONS These data suggest that LLLT is an effective biostimulator of ASCs in vascular regeneration, which enhances the survival of ASCs and stimulates the secretion of growth factors in skin flaps.
Collapse
Affiliation(s)
- In-Su Park
- Beckman Laser Institute Korea, Dankook University, Cheonan, Chungnam, Korea
| | - Arindam Mondal
- Beckman Laser Institute Korea, Dankook University, Cheonan, Chungnam, Korea
| | - Phil-Sang Chung
- Beckman Laser Institute Korea, Dankook University, Cheonan, Chungnam, Korea; Department of Otolaryngology-Head and Neck Surgery, College of Medicine, Dankook University, Cheonan, Chungnam, Korea
| | - Jin Chul Ahn
- Beckman Laser Institute Korea, Dankook University, Cheonan, Chungnam, Korea; Department of Biomedical Science, Dankook University, Cheonan, Chungnam, Korea; Biomedical Translational Research Institute, Dankook University, Cheonan, Chungnam, Korea.
| |
Collapse
|