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Liu J, Li Y, Zhang Y, Zhao Z, Liu B. Engineered stromal vascular fraction for tissue regeneration. Front Pharmacol 2025; 16:1510508. [PMID: 40183080 PMCID: PMC11966044 DOI: 10.3389/fphar.2025.1510508] [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: 10/13/2024] [Accepted: 02/19/2025] [Indexed: 04/05/2025] Open
Abstract
The treatment of various tissue injuries presents significant challenges, particularly in the reconstruction of large and severe tissue defects, with conventional clinical methods often yielding suboptimal results. However, advances in engineering materials have introduced new possibilities for tissue repair. Bioactive components are commonly integrated with synthetic materials to enhance tissue reconstruction. Stromal vascular fraction (SVF), an adipose-derived cell cluster, has shown considerable potential in tissue regeneration due to its simple and efficient way of obtaining and its richness in growth factors. Therefore, this review illustrated the preparation, characterization, mechanism of action, and applications of engineered SVF in various tissue repair processes, to provide some references for the option of better methods for tissue defect reconstruction.
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Affiliation(s)
- Jianfeng Liu
- Department of Hand and Foot Surgery, Orthopedics Center, The First Hospital of Jilin University, Changchun, China
- Engineering Laboratory of Tissue Engineering Biomaterials of Jilin Province, Changchun, China
| | - Yiwei Li
- Department of Hand and Foot Surgery, Orthopedics Center, The First Hospital of Jilin University, Changchun, China
- Engineering Laboratory of Tissue Engineering Biomaterials of Jilin Province, Changchun, China
| | - Yanan Zhang
- Department of Hand and Foot Surgery, Orthopedics Center, The First Hospital of Jilin University, Changchun, China
- Engineering Laboratory of Tissue Engineering Biomaterials of Jilin Province, Changchun, China
| | - Zhiwei Zhao
- Department of Hand and Foot Surgery, Orthopedics Center, The First Hospital of Jilin University, Changchun, China
- Engineering Laboratory of Tissue Engineering Biomaterials of Jilin Province, Changchun, China
| | - Bin Liu
- Department of Hand and Foot Surgery, Orthopedics Center, The First Hospital of Jilin University, Changchun, China
- Engineering Laboratory of Tissue Engineering Biomaterials of Jilin Province, Changchun, China
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Rehak L, Giurato L, Monami M, Meloni M, Scatena A, Panunzi A, Manti GM, Caravaggi CMF, Uccioli L. The Immune-Centric Revolution Translated into Clinical Application: Peripheral Blood Mononuclear Cell (PBMNC) Therapy in Diabetic Patients with No-Option Critical Limb-Threatening Ischemia (NO-CLTI)-Rationale and Meta-Analysis of Observational Studies. J Clin Med 2024; 13:7230. [PMID: 39685690 DOI: 10.3390/jcm13237230] [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: 09/10/2024] [Revised: 11/04/2024] [Accepted: 11/21/2024] [Indexed: 12/18/2024] Open
Abstract
Chronic limb-threatening ischemia (CLTI), the most advanced form of peripheral arterial disease (PAD), is the comorbidity primarily responsible for major lower-limb amputations, particularly for diabetic patients. Autologous cell therapy has been the focus of efforts over the past 20 years to create non-interventional therapeutic options for no-option CLTI to improve limb perfusion and wound healing. Among the different available techniques, peripheral blood mononuclear cells (PBMNC) appear to be the most promising autologous cell therapy due to physio-pathological considerations and clinical evidence, which will be discussed in this review. A meta-analysis of six clinical studies, including 256 diabetic patients treated with naive, fresh PBMNC produced via a selective filtration point-of-care device, was conducted. PBMNC was associated with a mean yearly amputation rate of 15.7%, a mean healing rate of 62%, and a time to healing of 208.6 ± 136.5 days. Moreover, an increase in TcPO2 and a reduction in pain were observed. All-cause mortality, with a mean rate of 22.2% and a yearly mortality rate of 18.8%, was reported. No serious adverse events were reported. Finally, some practical and financial considerations are provided, which point to the therapy's recommendation as the first line of treatment for this particular and crucial patient group.
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Affiliation(s)
- Laura Rehak
- Athena Cell Therapy Technologies, 50126 Florence, Italy
| | - Laura Giurato
- Department of Biomedicine and Prevention, Diabetes-Endocrine Section CTO Hospital, Tor Vergata University of Rome, 00133 Rome, Italy
| | - Matteo Monami
- Department of Diabetology Azienda Ospedaliera Universitaria Careggi, University of Florence, 50134 Florence, Italy
| | - Marco Meloni
- Diabetic Foot Unit, Department of Systems Medicine, Tor Vergata University of Rome, 00133 Rome, Italy
| | - Alessia Scatena
- Diabetology Unit, San Donato Hospital Arezzo, Local Health Authorities Southeast Tuscany, 52100 Arezzo, Italy
| | - Andrea Panunzi
- Department of Biomedicine and Prevention, Diabetes-Endocrine Section CTO Hospital, Tor Vergata University of Rome, 00133 Rome, Italy
- PhD School of Applied Medical and Surgical Sciences, University of Rome Tor Vergata Italy, 00133 Rome, Italy
| | | | | | - Luigi Uccioli
- Department of Biomedicine and Prevention, Diabetes-Endocrine Section CTO Hospital, Tor Vergata University of Rome, 00133 Rome, Italy
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Mundluru VK, Naidu MJ, Mundluru RT, Jeyaraman N, Muthu S, Ramasubramanian S, Jeyaraman M. Non-enzymatic methods for isolation of stromal vascular fraction and adipose-derived stem cells: A systematic review. World J Methodol 2024; 14:94562. [PMID: 38983657 PMCID: PMC11229868 DOI: 10.5662/wjm.v14.i2.94562] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2024] [Revised: 05/03/2024] [Accepted: 05/30/2024] [Indexed: 06/13/2024] Open
Abstract
BACKGROUND Adipose-derived stem cells (ADSCs) and the stromal vascular fraction (SVF) have garnered substantial interest in regenerative medicine due to their potential to treat a wide range of conditions. Traditional enzymatic methods for isolating these cells face challenges such as high costs, lengthy processing time, and regu-latory complexities. AIM This systematic review aimed to assess the efficacy and practicality of non-enzymatic, mechanical methods for isolating SVF and ADSCs, comparing these to conventional enzymatic approaches. METHODS Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a comprehensive literature search was conducted across multiple databases. Studies were selected based on inclusion criteria focused on non-enzymatic isolation methods for SVF and ADSCs from adipose tissue. The risk of bias was assessed, and a qualitative synthesis of findings was performed due to the methodological heterogeneity of the included studies. RESULTS Nineteen studies met the inclusion criteria, highlighting various mechanical techniques such as centrifugation, vortexing, and ultrasonic cavitation. The review identified significant variability in cell yield and viability, and the integrity of isolated cells across different non-enzymatic methods compared to enzymatic procedures. Despite some advantages of mechanical methods, including reduced processing time and avoidance of enzymatic reagents, the evidence suggests a need for optimization to match the cell quality and therapeutic efficacy achievable with enzymatic isolation. CONCLUSION Non-enzymatic, mechanical methods offer a promising alternative to enzymatic isolation of SVF and ADSCs, potentially simplifying the isolation process and reducing regulatory hurdles. However, further research is necessary to standardize these techniques and ensure consistent, high-quality cell yields for clinical applications. The development of efficient, safe, and reproducible non-enzymatic isolation methods could significantly advance the field of regenerative medicine.
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Affiliation(s)
- Vamsi Krishna Mundluru
- Department of Orthopaedics, MJ Naidu Super Speciality Hospital, Vijayawada 520002, Andhra Pradesh, India
- Department of Regenerative Medicine, StemC Clinics, Vijayawada 520002, Andhra Pradesh, India
| | - MJ Naidu
- Department of Orthopaedics, MJ Naidu Super Speciality Hospital, Vijayawada 520002, Andhra Pradesh, India
- Department of Regenerative Medicine, StemC Clinics, Vijayawada 520002, Andhra Pradesh, India
| | - Ravi Teja Mundluru
- Department of Orthopaedics, MJ Naidu Super Speciality Hospital, Vijayawada 520002, Andhra Pradesh, India
- Department of Regenerative Medicine, StemC Clinics, Vijayawada 520002, Andhra Pradesh, India
| | - Naveen Jeyaraman
- Department of Regenerative Medicine, StemC Clinics, Vijayawada 520002, Andhra Pradesh, India
- Department of Orthopaedics, ACS Medical College and Hospital, Dr. MGR Educational and Research Institute, Chennai 600077, Tamil Nadu, India
- Department of Orthopaedics, Orthopaedic Research Group, Coimbatore 641045, Tamil Nadu, India
| | - Sathish Muthu
- Department of Orthopaedics, Orthopaedic Research Group, Coimbatore 641045, Tamil Nadu, India
- Department of Orthopaedics, Government Medical College and Hospital, Karur 639004, Tamil Nadu, India
- Department of Biotechnology, Faculty of Engineering, Karpagam Academy of Higher Education, Coimbatore 641021, Tamil Nadu, India
| | - Swaminathan Ramasubramanian
- Department of Orthopaedics, Government Medical College, Omandurar Government Estate, Chennai 600002, Tamil Nadu, India
| | - Madhan Jeyaraman
- Department of Regenerative Medicine, StemC Clinics, Vijayawada 520002, Andhra Pradesh, India
- Department of Orthopaedics, ACS Medical College and Hospital, Dr. MGR Educational and Research Institute, Chennai 600077, Tamil Nadu, India
- Department of Orthopaedics, Orthopaedic Research Group, Coimbatore 641045, Tamil Nadu, India
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Yu W, Wang Z, Dai Y, Zhao S, Chen H, Wang S, Xie H. Autologous fat grafting for postoperative breast reconstruction: A systemic review. Regen Ther 2024; 26:1010-1017. [PMID: 39553540 PMCID: PMC11564784 DOI: 10.1016/j.reth.2024.10.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2024] [Revised: 09/22/2024] [Accepted: 10/10/2024] [Indexed: 11/19/2024] Open
Abstract
Autologous fat grafting technology has become a new method for breast reconstruction after breast surgery due to its advantages of simple operation, low immunogenicity, fewer complications, high patient acceptance, and natural filling effect. However, the unpredictable fate of transplanted fat limits its widespread application. Currently, many studies have made certain progress in improving the survival rate of fat grafts. This article provides an overview of autologous fat grafting technology, including the mechanisms of fat graft survival, techniques for obtaining and transplanting adipose tissue, methods for enhancing graft survival, and complications associated with fat grafting.
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Affiliation(s)
| | | | - Yuhan Dai
- Department of Breast Surgery, The First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China
| | - Shuhan Zhao
- Department of Breast Surgery, The First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China
| | - Huilin Chen
- Department of Breast Surgery, The First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China
| | - Shui Wang
- Department of Breast Surgery, The First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China
| | - Hui Xie
- Department of Breast Surgery, The First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China
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Bensemmane L, Milliat F, Treton X, Linard C. Systemically delivered adipose stromal vascular fraction mitigates radiation-induced gastrointestinal syndrome by immunomodulating the inflammatory response through a CD11b + cell-dependent mechanism. Stem Cell Res Ther 2023; 14:325. [PMID: 37953266 PMCID: PMC10641938 DOI: 10.1186/s13287-023-03562-7] [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: 03/01/2023] [Accepted: 11/07/2023] [Indexed: 11/14/2023] Open
Abstract
BACKGROUND Stromal vascular fraction (SVF) treatment promoted the regeneration of the intestinal epithelium, limiting lethality in a mouse model of radiation-induced gastrointestinal syndrome (GIS). The SVF has a heterogeneous cell composition; the effects between SVF and the host intestinal immunity are still unknown. The specific role of the different cells contained in the SVF needs to be clarified. Monocytes-macrophages have a crucial role in repair and monocyte recruitment and activation are orchestrated by the chemokine receptors CX3CR1 and CCR2. METHODS Mice exposed to abdominal radiation (18 Gy) received a single intravenous injection of SVF (2.5 × 106 cells), obtained by enzymatic digestion of inguinal fat tissue, on the day of irradiation. Intestinal immunity and regeneration were evaluated by flow cytometry, RT-PCR and histological analyses. RESULTS Using flow cytometry, we showed that SVF treatment modulated intestinal monocyte differentiation at 7 days post-irradiation by very early increasing the CD11b+Ly6C+CCR2+ population in the intestine ileal mucosa and accelerating the phenotype modification to acquire CX3CR1 in order to finally restore the F4/80+CX3CR1+ macrophage population. In CX3CR1-depleted mice, SVF treatment fails to mature the Ly6C-MCHII+CX3CR1+ population, leading to a macrophage population deficit associated with proinflammatory environment maintenance and defective intestinal repair; this impaired SVF efficiency on survival. Consistent with a CD11b+ being involved in SVF-induced intestinal repair, we showed that SVF-depleted CD11b+ treatment impaired F4/80+CX3CR1+macrophage pool restoration and caused loss of anti-inflammatory properties, abrogating stem cell compartment repair and survival. CONCLUSIONS These data showed that SVF treatment mitigates the GIS-involving immunomodulatory effect. Cooperation between the monocyte in SVF and the host monocyte defining the therapeutic properties of the SVF is necessary to guarantee the effective action of the SVF on the GIS.
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Affiliation(s)
- Lydia Bensemmane
- PSE-SANTE/SERAMED/LRMed, Institut de Radioprotection et de Sûreté Nucléaire (IRSN), 92260, Fontenay-Aux-Roses, France
| | - Fabien Milliat
- PSE-SANTE/SERAMED/LRMed, Institut de Radioprotection et de Sûreté Nucléaire (IRSN), 92260, Fontenay-Aux-Roses, France
| | | | - Christine Linard
- PSE-SANTE/SERAMED/LRMed, Institut de Radioprotection et de Sûreté Nucléaire (IRSN), 92260, Fontenay-Aux-Roses, France.
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Yuan Y, Fan Y, Zhou Y, Qiu R, Kang W, Liu Y, Chen Y, Wang C, Shi J, Liu C, Li Y, Wu M, Huang K, Liu Y, Zheng L. Linker histone variant H1.2 is a brake on white adipose tissue browning. Nat Commun 2023; 14:3982. [PMID: 37414781 PMCID: PMC10325996 DOI: 10.1038/s41467-023-39713-w] [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: 01/03/2023] [Accepted: 06/27/2023] [Indexed: 07/08/2023] Open
Abstract
Adipose-tissue is a central metabolic organ for whole-body energy homeostasis. Here, we find that highly expressed H1.2, a linker histone variant, senses thermogenic stimuli in beige and brown adipocytes. Adipocyte H1.2 regulates thermogenic genes in inguinal white-adipose-tissue (iWAT) and affects energy expenditure. Adipocyte H1.2 deletion (H1.2AKO) male mice show promoted iWAT browning and improved cold tolerance; while overexpressing H1.2 shows opposite effects. Mechanistically, H1.2 binds to the promoter of Il10rα, which encodes an Il10 receptor, and positively regulates its expression to suppress thermogenesis in a beige cell autonomous manner. Il10rα overexpression in iWAT negates cold-enhanced browning of H1.2AKO male mice. Increased H1.2 level is also found in WAT of obese humans and male mice. H1.2AKO male mice show alleviated fat accumulation and glucose intolerance in long-term normal chow-fed and high fat diet-fed conditions; while Il10rα overexpression abolishes these effects. Here, we show a metabolic function of H1.2-Il10rα axis in iWAT.
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Affiliation(s)
- Yangmian Yuan
- Hubei Key Laboratory of Cell Homeostasis, Frontier Science Center for Immunology and Metabolism, College of Life Sciences, Wuhan University, 430072, Wuhan, China
| | - Yu Fan
- Hubei Key Laboratory of Cell Homeostasis, Frontier Science Center for Immunology and Metabolism, College of Life Sciences, Wuhan University, 430072, Wuhan, China
| | - Yihao Zhou
- Hubei Key Laboratory of Cell Homeostasis, Frontier Science Center for Immunology and Metabolism, College of Life Sciences, Wuhan University, 430072, Wuhan, China
| | - Rong Qiu
- Hubei Key Laboratory of Cell Homeostasis, Frontier Science Center for Immunology and Metabolism, College of Life Sciences, Wuhan University, 430072, Wuhan, China
| | - Wei Kang
- Hubei Key Laboratory of Cell Homeostasis, Frontier Science Center for Immunology and Metabolism, College of Life Sciences, Wuhan University, 430072, Wuhan, China
| | - Yu Liu
- Hubei Key Laboratory of Cell Homeostasis, Frontier Science Center for Immunology and Metabolism, College of Life Sciences, Wuhan University, 430072, Wuhan, China
| | - Yuchen Chen
- School of Pharmacy, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Huazhong University of Science and Technology, 430030, Wuhan, China
| | - Chenyu Wang
- Hubei Key Laboratory of Cell Homeostasis, Frontier Science Center for Immunology and Metabolism, College of Life Sciences, Wuhan University, 430072, Wuhan, China
| | - Jiajian Shi
- School of Pharmacy, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Huazhong University of Science and Technology, 430030, Wuhan, China
| | - Chengyu Liu
- Department of Transfusion Medicine, Wuhan Hospital of Traditional Chinese and Western Medicine, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, China
| | - Yangkai Li
- Department of Thoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, China
| | - Min Wu
- Hubei Key Laboratory of Cell Homeostasis, Frontier Science Center for Immunology and Metabolism, College of Life Sciences, Wuhan University, 430072, Wuhan, China
| | - Kun Huang
- School of Pharmacy, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Huazhong University of Science and Technology, 430030, Wuhan, China
| | - Yong Liu
- Hubei Key Laboratory of Cell Homeostasis, Frontier Science Center for Immunology and Metabolism, College of Life Sciences, Wuhan University, 430072, Wuhan, China
| | - Ling Zheng
- Hubei Key Laboratory of Cell Homeostasis, Frontier Science Center for Immunology and Metabolism, College of Life Sciences, Wuhan University, 430072, Wuhan, China.
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Bonanni M, Rehak L, Massaro G, Benedetto D, Matteucci A, Russo G, Esperto F, Federici M, Mauriello A, Sangiorgi GM. Autologous Immune Cell-Based Regenerative Therapies to Treat Vasculogenic Erectile Dysfunction: Is the Immuno-Centric Revolution Ready for the Prime Time? Biomedicines 2022; 10:biomedicines10051091. [PMID: 35625828 PMCID: PMC9138496 DOI: 10.3390/biomedicines10051091] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2022] [Revised: 04/30/2022] [Accepted: 05/02/2022] [Indexed: 02/04/2023] Open
Abstract
About 35% of patients affected by erectile dysfunction (ED) do not respond to oral phosphodiesterase-5 inhibitors (PDE5i) and more severe vasculogenic refractory ED affects diabetic patients. Innovative approaches, such as regenerative therapies, including stem cell therapy (SCT) and platelet-rich plasma (PRP), are currently under investigation. Recent data point out that the regenerative capacity of stem cells is strongly influenced by local immune responses, with macrophages playing a pivotal role in the injury response and as a coordinator of tissue regeneration, suggesting that control of the immune response could be an appealing approach in regenerative medicine. A new generation of autologous cell therapy based on immune cells instead of stem cells, which could change regenerative medicine for good, is discussed. Increasing safety and efficacy data are coming from clinical trials using peripheral blood mononuclear cells to treat no-option critical limb ischemia and diabetic foot. In this review, ongoing phase 1/phase 2 stem cell clinical trials are discussed. In addition, we examine the mechanism of action and rationale, as well as propose a new generation of regenerative therapies, evolving from typical stem cell or growth factor to immune cell-based medicine, based on autologous peripheral blood mononuclear cells (PBMNC) concentrates for the treatment of ED.
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Affiliation(s)
- Michela Bonanni
- Department of Biomedicine and Prevention, Institute of Cardiology, University of Rome Tor Vergata, 00133 Rome, Italy; (M.B.); (G.M.); (D.B.); (A.M.); (G.R.)
| | - Laura Rehak
- Athena Biomedical Innovations, 50126 Florence, Italy;
| | - Gianluca Massaro
- Department of Biomedicine and Prevention, Institute of Cardiology, University of Rome Tor Vergata, 00133 Rome, Italy; (M.B.); (G.M.); (D.B.); (A.M.); (G.R.)
| | - Daniela Benedetto
- Department of Biomedicine and Prevention, Institute of Cardiology, University of Rome Tor Vergata, 00133 Rome, Italy; (M.B.); (G.M.); (D.B.); (A.M.); (G.R.)
| | - Andrea Matteucci
- Department of Biomedicine and Prevention, Institute of Cardiology, University of Rome Tor Vergata, 00133 Rome, Italy; (M.B.); (G.M.); (D.B.); (A.M.); (G.R.)
- Division of Cardiology San Filippo Neri Hospital, 00135 Rome, Italy
| | - Giulio Russo
- Department of Biomedicine and Prevention, Institute of Cardiology, University of Rome Tor Vergata, 00133 Rome, Italy; (M.B.); (G.M.); (D.B.); (A.M.); (G.R.)
| | | | - Massimo Federici
- Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy;
| | - Alessandro Mauriello
- Department of Experimental Medicine, University of Rome Tor Vergata, 00133 Rome, Italy;
| | - Giuseppe Massimo Sangiorgi
- Department of Biomedicine and Prevention, Institute of Cardiology, University of Rome Tor Vergata, 00133 Rome, Italy; (M.B.); (G.M.); (D.B.); (A.M.); (G.R.)
- Correspondence:
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Guerrero J, Dasen B, Frismantiene A, Pigeot S, Ismail T, Schaefer DJ, Philippova M, Resink TJ, Martin I, Scherberich A. OUP accepted manuscript. Stem Cells Transl Med 2022; 11:213-229. [PMID: 35259280 PMCID: PMC8929526 DOI: 10.1093/stcltm/szab021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2021] [Accepted: 10/31/2021] [Indexed: 11/24/2022] Open
Abstract
Cells of the stromal vascular fraction (SVF) of human adipose tissue have the capacity to generate osteogenic grafts with intrinsic vasculogenic properties. However, cultured adipose-derived stromal cells (ASCs), even after minimal monolayer expansion, lose osteogenic capacity in vivo. Communication between endothelial and stromal/mesenchymal cell lineages has been suggested to improve bone formation and vascularization by engineered tissues. Here, we investigated the specific role of a subpopulation of SVF cells positive for T-cadherin (T-cad), a putative endothelial marker. We found that maintenance during monolayer expansion of a T-cad-positive cell population, composed of endothelial lineage cells (ECs), is mandatory to preserve the osteogenic capacity of SVF cells in vivo and strongly supports their vasculogenic properties. Depletion of T-cad-positive cells from the SVF totally impaired bone formation in vivo and strongly reduced vascularization by SVF cells in association with decreased VEGF and Adiponectin expression. The osteogenic potential of T-cad-depleted SVF cells was fully rescued by co-culture with ECs from a human umbilical vein (HUVECs), constitutively expressing T-cad. Ectopic expression of T-cad in ASCs stimulated mineralization in vitro but failed to rescue osteogenic potential in vivo, indicating that the endothelial nature of the T-cad-positive cells is the key factor for induction of osteogenesis in engineered grafts based on SVF cells. This study demonstrates that crosstalk between stromal and T-cad expressing endothelial cells within adipose tissue critically regulates osteogenesis, with VEGF and adiponectin as associated molecular mediators.
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Affiliation(s)
- Julien Guerrero
- Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Boris Dasen
- Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Agne Frismantiene
- Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Sebastien Pigeot
- Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Tarek Ismail
- Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland
- Department of Plastic, Reconstructive, Aesthetic and Hand Surgery, University Hospital Basel, Basel, Switzerland
| | - Dirk J Schaefer
- Department of Plastic, Reconstructive, Aesthetic and Hand Surgery, University Hospital Basel, Basel, Switzerland
| | - Maria Philippova
- Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Therese J Resink
- Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Ivan Martin
- Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Arnaud Scherberich
- Corresponding author: Arnaud Scherberich, Department of Biomedicine, Hebelstrasse 20, University Hospital Basel, 4031 Basel, Switzerland. Tel: +41 061 328 73 75;
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Magenta A, Florio MC, Ruggeri M, Furgiuele S. Autologous cell therapy in diabetes‑associated critical limb ischemia: From basic studies to clinical outcomes (Review). Int J Mol Med 2021; 48:173. [PMID: 34278463 DOI: 10.3892/ijmm.2021.5006] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2020] [Accepted: 09/30/2020] [Indexed: 01/13/2023] Open
Abstract
Cell therapy is becoming an attractive alternative for the treatment of patients with no‑option critical limb ischemia (CLI). The main benefits of cell therapy are the induction of therapeutic angiogenesis and neovascularization that lead to an increase in blood flow in the ischemic limb and tissue regeneration in non‑healing cutaneous trophic lesions. In the present review, the current state of the art of strategies in the cell therapy field are summarized, focusing on intra‑operative autologous cell concentrates in diabetic patients with CLI, examining different sources of cell concentrates and their mechanisms of action. The present study underlined the detrimental effects of the diabetic condition on different sources of autologous cells used in cell therapy, and also in delaying wound healing capacity. Moreover, relevant clinical trials and critical issues arising from cell therapy trials are discussed. Finally, the new concept of cell therapy as an adjuvant therapy to increase wound healing in revascularized diabetic patients is introduced.
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Affiliation(s)
| | - Maria Cristina Florio
- Laboratory of Cardiovascular Science, National Institute on Aging (NIA), National Institutes of Health (NIH), Baltimore, MD 21224, USA
| | - Massimo Ruggeri
- Department of Vascular Surgery, San Camillo de Lellis Hospital, I‑02100 Rieti, Italy
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François P, Rusconi G, Arnaud L, Mariotta L, Giraudo L, Minonzio G, Veran J, Bertrand B, Dumoulin C, Grimaud F, Lyonnet L, Casanova D, Giverne C, Cras A, Magalon G, Dignat-George F, Sabatier F, Magalon J, Soldati G. Inter-center comparison of good manufacturing practices-compliant stromal vascular fraction and proposal for release acceptance criteria: a review of 364 productions. Stem Cell Res Ther 2021; 12:373. [PMID: 34210363 PMCID: PMC8252207 DOI: 10.1186/s13287-021-02445-z] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2021] [Accepted: 06/10/2021] [Indexed: 11/10/2022] Open
Abstract
Background Even though the manufacturing processes of the stromal vascular fraction for clinical use are performed in compliance with the good manufacturing practices applying to advanced therapy medicinal products, specifications related to stromal vascular fraction quality remain poorly defined. We analyzed stromal vascular fraction clinical batches from two independent good manufacturing practices-compliant manufacturing facilities, the Swiss Stem Cell Foundation (SSCF) and Marseille University Hospitals (AP-HM), with the goal of defining appropriate and harmonized release acceptance criteria. Methods This retrospective analysis reviewed the biological characteristics of 364 batches of clinical-grade stromal vascular fraction. Collected data included cell viability, recovery yield, cell subset distribution of stromal vascular fraction, and microbiological quality. Results Stromal vascular fraction from SSCF cohort demonstrated a higher viability (89.33% ± 4.30%) and recovery yield (2.54 × 105 ± 1.22 × 105 viable nucleated cells (VNCs) per mL of adipose tissue) than stromal vascular fraction from AP-HM (84.20% ± 5.96% and 2.25 × 105 ± 1.11 × 105 VNCs per mL). AP-HM batches were significantly less contaminated (95.71% of sterile batches versus 74.15% for SSCF batches). The cell subset distribution was significantly different (higher proportion of endothelial cells and lower proportion of leukocytes and pericytes in SSCF cohort). Conclusions Both centers agreed that a good manufacturing practices-compliant stromal vascular fraction batch should exert a viability equal or superior to 80%, a minimum recovery yield of 1.50 × 105 VNCs per mL of adipose tissue, a proportion of adipose-derived stromal cells at least equal to 20%, and a proportion of leukocytes under 50%. In addition, a multiparameter gating strategy for stromal vascular fraction analysis is proposed. Supplementary Information The online version contains supplementary material available at 10.1186/s13287-021-02445-z.
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Affiliation(s)
- Pauline François
- Cell Therapy Department, Hôpital de la Conception, AP-HM, INSERM CIC BT 1409, 147 Bd Baille, 13005, Marseille, France.,Aix Marseille Univ, INSERM, INRA, C2VN, Marseille, France
| | - Giulio Rusconi
- Swiss Stem Cell Foundation, Gentilino, Lugano, Switzerland.,Department of Biotechnology and Life Sciences, University of Insubria, Varese, Italy
| | - Laurent Arnaud
- Vascular Biology Department, Hôpital de la Conception, AP-HM, Marseille, France
| | - Luca Mariotta
- Swiss Stem Cell Foundation, Gentilino, Lugano, Switzerland
| | - Laurent Giraudo
- Cell Therapy Department, Hôpital de la Conception, AP-HM, INSERM CIC BT 1409, 147 Bd Baille, 13005, Marseille, France
| | - Greta Minonzio
- Swiss Stem Cell Foundation, Gentilino, Lugano, Switzerland
| | - Julie Veran
- Cell Therapy Department, Hôpital de la Conception, AP-HM, INSERM CIC BT 1409, 147 Bd Baille, 13005, Marseille, France
| | - Baptiste Bertrand
- Plastic Surgery Department, Hôpital de la Conception, AP-HM, Marseille, France
| | - Chloé Dumoulin
- Cell Therapy Department, Hôpital de la Conception, AP-HM, INSERM CIC BT 1409, 147 Bd Baille, 13005, Marseille, France
| | - Fanny Grimaud
- Cell Therapy Department, Hôpital de la Conception, AP-HM, INSERM CIC BT 1409, 147 Bd Baille, 13005, Marseille, France
| | - Luc Lyonnet
- Vascular Biology Department, Hôpital de la Conception, AP-HM, Marseille, France
| | - Dominique Casanova
- Plastic Surgery Department, Hôpital de la Conception, AP-HM, Marseille, France
| | - Camille Giverne
- Normandie Univ, UNIROUEN, INSERM, U1234, Rouen University Hospital, Department of Immunology and Biotherapy, Rouen, France
| | - Audrey Cras
- Assistance Publique-Hôpitaux de Paris, Saint-Louis Hospital, Cell Therapy Unit, Cord blood Bank and CIC-BT501, Paris, France
| | | | - Françoise Dignat-George
- Aix Marseille Univ, INSERM, INRA, C2VN, Marseille, France.,Vascular Biology Department, Hôpital de la Conception, AP-HM, Marseille, France
| | - Florence Sabatier
- Cell Therapy Department, Hôpital de la Conception, AP-HM, INSERM CIC BT 1409, 147 Bd Baille, 13005, Marseille, France.,Aix Marseille Univ, INSERM, INRA, C2VN, Marseille, France.,Remedex, Marseille, France
| | - Jeremy Magalon
- Cell Therapy Department, Hôpital de la Conception, AP-HM, INSERM CIC BT 1409, 147 Bd Baille, 13005, Marseille, France. .,Aix Marseille Univ, INSERM, INRA, C2VN, Marseille, France. .,Remedex, Marseille, France.
| | - Gianni Soldati
- Swiss Stem Cell Foundation, Gentilino, Lugano, Switzerland
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Abstract
PURPOSE OF REVIEW Immunotherapy strategies alternative to current antiretroviral therapies will need to address viral diversity while increasing the immune system's ability to efficiently target the latent virus reservoir. Antibody-based molecules can be designed based on broadly neutralizing and non-neutralizing antibodies that target free virions and infected cells. These multispecific molecules, either by IgG-like or non-IgG-like in structure, aim to target several independent HIV-1 epitopes and/or engage effector cells to eliminate the replicating virus and infected cells. This detailed review is intended to stimulate discussion on future requirements for novel immunotherapeutic molecules. RECENT FINDINGS Bispecific and trispecific antibodies are engineered as a single molecules to target two or more independent epitopes on the HIV-1 envelope (Env). These antibody-based molecules have increased avidity for Env, leading to improved neutralization potency and breadth compared with single parental antibodies. Furthermore, bispecific and trispecific antibodies that engage cellular receptors with one arm of the molecule help concentrate inhibitory molecules to the sites of potential infection and facilitate engagement of immune effector cells and Env-expressing target cells for their elimination. SUMMARY Recently engineered antibody-based molecules of different sizes and structures show promise in vitro or in vivo and are encouraging candidates for HIV treatment.
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Affiliation(s)
- Marina Tuyishime
- Department of Surgery, Duke University Medical Center, Durham, NC, USA
| | - Guido Ferrari
- Department of Surgery, Duke University Medical Center, Durham, NC, USA
- Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC, USA
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Frapin L, Clouet J, Chédeville C, Moraru C, Samarut E, Henry N, André M, Bord E, Halgand B, Lesoeur J, Fusellier M, Guicheux J, Le Visage C. Controlled release of biological factors for endogenous progenitor cell migration and intervertebral disc extracellular matrix remodelling. Biomaterials 2020; 253:120107. [PMID: 32450408 DOI: 10.1016/j.biomaterials.2020.120107] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2019] [Revised: 04/20/2020] [Accepted: 05/06/2020] [Indexed: 02/06/2023]
Abstract
The recent description of resident stem/progenitor cells in degenerated intervertebral discs (IVDs) supports the notion that their regenerative capacities could be harnessed to stimulate endogenous repair of the nucleus pulposus (NP). In this study, we developed a delivery system based on pullulan microbeads (PMBs) for sequential release of the chemokine CCL-5 to recruit these disc stem/progenitor cells to the NP tissue, followed by the release of the growth factors TGF-β1 and GDF-5 to induce the synthesis of a collagen type II- and aggrecan-rich extracellular matrix (ECM). Bioactivity of released CCL5 on human adipose-derived stem cells (hASCs), selected to mimic disc stem/progenitors, was demonstrated using a Transwell® chemotaxis assay. The regenerative effects of loaded PMBs were investigated in ex vivo spontaneously degenerated ovine IVDs. Fluorescent hASCs were seeded on the top cartilaginous endplates (CEPs); the degenerated NPs were injected with PMBs loaded with CCL5, TGF-β1, and GDF-5; and the IVDs were then cultured for 3, 7, and 28 days to allow for cell migration and disc regeneration. The PMBs exhibited sustained release of biological factors for 21 days. Ex vivo migration of seeded hASCs from the CEP toward the NP was demonstrated, with the cells migrating a significantly greater distance when loaded PMBs were injected (5.8 ± 1.3 mm vs. 3.5 ± 1.8 mm with no injection of PMBs). In ovine IVDs, the overall NP cellularity, the collagen type II and the aggrecan staining intensities, and the Tie2+ progenitor cell density in the NP were increased at day 28 compared to the control groups. Considered together, PMBs loaded with CCL5/TGF-β1/GDF-5 constitute an innovative and promising strategy for controlled release of growth factors to promote cell recruitment and extracellular matrix remodelling.
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Affiliation(s)
- Leslie Frapin
- Inserm, UMR 1229, RMeS, Regenerative Medicine and Skeleton, Université de Nantes, ONIRIS, Nantes, F-44042, France; Université de Nantes, UFR Odontologie, Nantes, F-44042, France
| | - Johann Clouet
- Inserm, UMR 1229, RMeS, Regenerative Medicine and Skeleton, Université de Nantes, ONIRIS, Nantes, F-44042, France; Université de Nantes, UFR Odontologie, Nantes, F-44042, France; CHU Nantes, Pharmacie Centrale, PHU 11, Nantes, F-44093, France; Université de Nantes, UFR Sciences Biologiques et Pharmaceutiques, Nantes, F-44035, France
| | - Claire Chédeville
- Inserm, UMR 1229, RMeS, Regenerative Medicine and Skeleton, Université de Nantes, ONIRIS, Nantes, F-44042, France; Université de Nantes, UFR Odontologie, Nantes, F-44042, France
| | - Constantin Moraru
- Inserm, UMR 1229, RMeS, Regenerative Medicine and Skeleton, Université de Nantes, ONIRIS, Nantes, F-44042, France; Université de Nantes, UFR Odontologie, Nantes, F-44042, France; CHU Nantes, Service de Neurotraumatologie, PHU4 OTONN, Nantes, F-44093, France
| | - Edouard Samarut
- Inserm, UMR 1229, RMeS, Regenerative Medicine and Skeleton, Université de Nantes, ONIRIS, Nantes, F-44042, France; Université de Nantes, UFR Odontologie, Nantes, F-44042, France; CHU Nantes, Service de Neurotraumatologie, PHU4 OTONN, Nantes, F-44093, France
| | - Nina Henry
- Inserm, UMR 1229, RMeS, Regenerative Medicine and Skeleton, Université de Nantes, ONIRIS, Nantes, F-44042, France; Université de Nantes, UFR Odontologie, Nantes, F-44042, France
| | - Manon André
- Inserm, UMR 1229, RMeS, Regenerative Medicine and Skeleton, Université de Nantes, ONIRIS, Nantes, F-44042, France; Université de Nantes, UFR Odontologie, Nantes, F-44042, France; SC3M -"Electron Microscopy, Microcharacterization, and Functional Morphohistology Imaging" Core Facility, Structure Fédérative de Recherche François Bonamy, INSERM - UMS016, CNRS 3556, CHU Nantes, Université de Nantes, Nantes, Nantes, F-04402, France
| | - Eric Bord
- Inserm, UMR 1229, RMeS, Regenerative Medicine and Skeleton, Université de Nantes, ONIRIS, Nantes, F-44042, France; Université de Nantes, UFR Odontologie, Nantes, F-44042, France; CHU Nantes, Service de Neurotraumatologie, PHU4 OTONN, Nantes, F-44093, France
| | - Boris Halgand
- Inserm, UMR 1229, RMeS, Regenerative Medicine and Skeleton, Université de Nantes, ONIRIS, Nantes, F-44042, France; Université de Nantes, UFR Odontologie, Nantes, F-44042, France; CHU Nantes, PHU4 OTONN, Nantes, F-44093, France
| | - Julie Lesoeur
- Inserm, UMR 1229, RMeS, Regenerative Medicine and Skeleton, Université de Nantes, ONIRIS, Nantes, F-44042, France; Université de Nantes, UFR Odontologie, Nantes, F-44042, France; SC3M -"Electron Microscopy, Microcharacterization, and Functional Morphohistology Imaging" Core Facility, Structure Fédérative de Recherche François Bonamy, INSERM - UMS016, CNRS 3556, CHU Nantes, Université de Nantes, Nantes, Nantes, F-04402, France
| | - Marion Fusellier
- Inserm, UMR 1229, RMeS, Regenerative Medicine and Skeleton, Université de Nantes, ONIRIS, Nantes, F-44042, France; Université de Nantes, UFR Odontologie, Nantes, F-44042, France; Department of Diagnostic Imaging, CRIP, National Veterinary School (ONIRIS), Nantes, F-44307, France
| | - Jérôme Guicheux
- Inserm, UMR 1229, RMeS, Regenerative Medicine and Skeleton, Université de Nantes, ONIRIS, Nantes, F-44042, France; Université de Nantes, UFR Odontologie, Nantes, F-44042, France; SC3M -"Electron Microscopy, Microcharacterization, and Functional Morphohistology Imaging" Core Facility, Structure Fédérative de Recherche François Bonamy, INSERM - UMS016, CNRS 3556, CHU Nantes, Université de Nantes, Nantes, Nantes, F-04402, France; CHU Nantes, PHU4 OTONN, Nantes, F-44093, France.
| | - Catherine Le Visage
- Inserm, UMR 1229, RMeS, Regenerative Medicine and Skeleton, Université de Nantes, ONIRIS, Nantes, F-44042, France; Université de Nantes, UFR Odontologie, Nantes, F-44042, France.
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Stefanis AJ, Groh T, Arenbergerova M, Arenberger P, Bauer PO. Stromal Vascular Fraction and its Role in the Management of Alopecia: A Review. THE JOURNAL OF CLINICAL AND AESTHETIC DERMATOLOGY 2019; 12:35-44. [PMID: 32038756 PMCID: PMC6937163] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 06/10/2023]
Abstract
Adipose cells organized in small clusters under the reticular dermis closely interact with hair follicular cells and regulate the hair cycle. Intradermal adipocyte progenitor cells are activated toward the end of the telogen phase to proliferate and differentiate into mature adipocytes. These cells, surrounding the hair follicles, secrete signaling molecules that control the progression of the hair cycle. Diseases associated with defects in adipocyte homeostasis, such as lipodystrophy and focal dermal hypoplasia, lead to alopecia. In this review, we discuss the potential influence of stromal vascular fraction from adipose tissue in the management of alopecia as well as its involvement in preclinical and clinical trials.
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Affiliation(s)
- Athanasios J Stefanis
- Drs. Stefanis, Arenbergerova, and Arenberger are with the Department of Dermatology and Venereology, Faculty Hospital Kralovske Vinohrady and Third Medical Faculty of Charles University in Prague, the Czech Republic
- Drs. Groh and Bauer are with Bioinova, Ltd. in Prague, the Czech Republic
| | - Tomas Groh
- Drs. Stefanis, Arenbergerova, and Arenberger are with the Department of Dermatology and Venereology, Faculty Hospital Kralovske Vinohrady and Third Medical Faculty of Charles University in Prague, the Czech Republic
- Drs. Groh and Bauer are with Bioinova, Ltd. in Prague, the Czech Republic
| | - Monika Arenbergerova
- Drs. Stefanis, Arenbergerova, and Arenberger are with the Department of Dermatology and Venereology, Faculty Hospital Kralovske Vinohrady and Third Medical Faculty of Charles University in Prague, the Czech Republic
- Drs. Groh and Bauer are with Bioinova, Ltd. in Prague, the Czech Republic
| | - Petr Arenberger
- Drs. Stefanis, Arenbergerova, and Arenberger are with the Department of Dermatology and Venereology, Faculty Hospital Kralovske Vinohrady and Third Medical Faculty of Charles University in Prague, the Czech Republic
- Drs. Groh and Bauer are with Bioinova, Ltd. in Prague, the Czech Republic
| | - Peter O Bauer
- Drs. Stefanis, Arenbergerova, and Arenberger are with the Department of Dermatology and Venereology, Faculty Hospital Kralovske Vinohrady and Third Medical Faculty of Charles University in Prague, the Czech Republic
- Drs. Groh and Bauer are with Bioinova, Ltd. in Prague, the Czech Republic
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14
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Abstract
Adipose stem cells (ASCs) are the basis of procedures intended for tissue regeneration. These cells are heterogeneous, owing to various factors, including the donor age, sex, body mass index, and clinical condition; the isolation procedure (liposuction or fat excision); the place from where the cells were sampled (body site and depth of each adipose depot); culture surface; type of medium (whether supplemented with fetal bovine serum or xeno-free), that affect the principal phenotypic features of ASCs. The features related to ASCs heterogeneity are relevant for the success of therapeutic procedures; these features include proliferation capacity, differentiation potential, immunophenotype, and the secretome. These are important characteristics for the success of regenerative tissue engineering, not only because of their effects upon the reconstruction and healing exerted by ASCs themselves, but also because of the paracrine signaling of ASCs and its impact on recipient tissues. Knowledge of sources of heterogeneity will be helpful in the standardization of ASCs-based procedures. New avenues of research could include evaluation of the effects of the use of more homo1geneous ASCs for specific purposes, the study of ASCs-recipient interactions in heterologous cell transplantation, and the characterization of epigenetic changes in ASCs, as well as investigations of the effect of the metabolome upon ASCs behavior in culture.
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15
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Magalon J, Velier M, Simoncini S, François P, Bertrand B, Daumas A, Benyamine A, Boissier R, Arnaud L, Lyonnet L, Fernandez S, Dignat-George F, Casanova D, Guillet B, Granel B, Paul P, Sabatier F. Molecular profile and proangiogenic activity of the adipose-derived stromal vascular fraction used as an autologous innovative medicinal product in patients with systemic sclerosis. Ann Rheum Dis 2019; 78:391-398. [PMID: 30612118 DOI: 10.1136/annrheumdis-2018-214218] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2018] [Revised: 10/31/2018] [Accepted: 11/16/2018] [Indexed: 12/11/2022]
Abstract
OBJECTIVE The autologous stromal vascular fraction (SVF) from adipose tissue is an alternative to cultured adipose-derived stem cells for use in regenerative medicine and represents a promising therapy for vasculopathy and hand disability in systemic sclerosis (SSc). However, the bioactivity of autologous SVF is not documented in this disease context. This study aimed to compare the molecular and functional profiles of the SVF-based medicinal product obtained from SSc and healthy subjects. METHODS Good manufacturing practice (GMP)-grade SVF from 24 patients with SSc and 12 healthy donors (HD) was analysed by flow cytometry to compare the distribution of the CD45- and CD45+ haematopoietic cell subsets. The ability of SVF to form a vascular network was assessed using Matrigel in vivo assay. The transcriptomic and secretory profiles of the SSc-SVF were assessed by RNA sequencing and multiplex analysis, respectively, and were compared with the HD-SVF. RESULTS The distribution of the leucocyte, endothelial, stromal, pericyte and transitional cell subsets was similar for SSc-SVF and HD-SVF. SSc-SVF retained its vasculogenic capacity, but the density of neovessels formed in SVF-loaded Matrigel implanted in nude mice was slightly decreased compared with HD-SVF. SSc-SVF displayed a differential molecular signature reflecting deregulation of angiogenesis, endothelial activation and fibrosis. CONCLUSIONS Our study provides the first evidence that SSc does not compromise the vascular repair capacity of SVF, supporting its use as an innovative autologous biotherapy. The characterisation of the specific SSc-SVF molecular profile provides new perspectives for delineating markers of the potency of SVF and its targets for the treatment of SSc.
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Affiliation(s)
- Jérémy Magalon
- Cell Therapy Department, Hôpital de la Conception, AP-HM, INSERM CIC BT 1409, Marseille, France
- INSERM, INRA, C2VN, Aix-Marseille University, Marseille, France
| | - Mélanie Velier
- Cell Therapy Department, Hôpital de la Conception, AP-HM, INSERM CIC BT 1409, Marseille, France
- INSERM, INRA, C2VN, Aix-Marseille University, Marseille, France
| | | | - Pauline François
- Cell Therapy Department, Hôpital de la Conception, AP-HM, INSERM CIC BT 1409, Marseille, France
- INSERM, INRA, C2VN, Aix-Marseille University, Marseille, France
| | - Baptiste Bertrand
- INSERM, INRA, C2VN, Aix-Marseille University, Marseille, France
- Plastic Surgery Department, Hôpital de la Conception, AP-HM, Marseille, France
| | - Aurélie Daumas
- Internal Medicine Department, Hôpital Nord & Hôpital de la Timone, AP-HM, Marseille, France
| | - Audrey Benyamine
- INSERM, INRA, C2VN, Aix-Marseille University, Marseille, France
- Internal Medicine Department, Hôpital Nord & Hôpital de la Timone, AP-HM, Marseille, France
| | - Romain Boissier
- INSERM, INRA, C2VN, Aix-Marseille University, Marseille, France
- Urology Surgery Department, Hôpital de la Conception, AP-HM, Marseille, France
| | - Laurent Arnaud
- Vascular Biology Department, Hôpital de la Conception, AP-HM, Marseille, France
| | - Luc Lyonnet
- Vascular Biology Department, Hôpital de la Conception, AP-HM, Marseille, France
| | | | - Françoise Dignat-George
- INSERM, INRA, C2VN, Aix-Marseille University, Marseille, France
- Vascular Biology Department, Hôpital de la Conception, AP-HM, Marseille, France
| | - Dominique Casanova
- Plastic Surgery Department, Hôpital de la Conception, AP-HM, Marseille, France
| | - Benjamin Guillet
- INSERM, INRA, C2VN, Aix-Marseille University, Marseille, France
- CERIMED, Aix-Marseille University, AP-HM, Marseille, France
| | - Brigitte Granel
- INSERM, INRA, C2VN, Aix-Marseille University, Marseille, France
- Internal Medicine Department, Hôpital Nord & Hôpital de la Timone, AP-HM, Marseille, France
| | - Pascale Paul
- Cell Therapy Department, Hôpital de la Conception, AP-HM, INSERM CIC BT 1409, Marseille, France
- INSERM, INRA, C2VN, Aix-Marseille University, Marseille, France
| | - Florence Sabatier
- Cell Therapy Department, Hôpital de la Conception, AP-HM, INSERM CIC BT 1409, Marseille, France
- INSERM, INRA, C2VN, Aix-Marseille University, Marseille, France
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Ramakrishnan VM, Boyd NL. The Adipose Stromal Vascular Fraction as a Complex Cellular Source for Tissue Engineering Applications. TISSUE ENGINEERING. PART B, REVIEWS 2018; 24:289-299. [PMID: 28316259 PMCID: PMC6080106 DOI: 10.1089/ten.teb.2017.0061] [Citation(s) in RCA: 86] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/06/2017] [Accepted: 03/17/2017] [Indexed: 12/27/2022]
Abstract
A major challenge in tissue engineering is the generation of sufficient volumes of viable tissue for organ transplant. The development of a stable, mature vasculature is required to sustain the metabolic and functional activities of engineered tissues. Adipose stromal vascular fraction (SVF) cells are an easily accessible, heterogeneous cell system comprised of endothelial cells, macrophages, pericytes, and various stem cell populations. Collectively, SVF has been shown to spontaneously form vessel-like networks in vitro and robust, patent, and functional vasculatures in vivo. Capitalizing on this ability, we and others have demonstrated adipose SVF's utility in generating and augmenting engineered liver, cardiac, and vascular tissues, to name a few. This review highlights the scientific origins of SVF, the use of SVF as a clinically relevant vascular source, various SVF constituents and their roles, and practical considerations associated with isolating SVF for various tissue engineering applications.
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Affiliation(s)
- Venkat M. Ramakrishnan
- Cardiovascular Innovation Institute, Department of Physiology, University of Louisville School of Medicine, Louisville, Kentucky
| | - Nolan L. Boyd
- Cardiovascular Innovation Institute, Department of Physiology, University of Louisville School of Medicine, Louisville, Kentucky
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Kilinc MO, Santidrian A, Minev I, Toth R, Draganov D, Nguyen D, Lander E, Berman M, Minev B, Szalay AA. The ratio of ADSCs to HSC-progenitors in adipose tissue derived SVF may provide the key to predict the outcome of stem-cell therapy. Clin Transl Med 2018; 7:5. [PMID: 29417261 PMCID: PMC5803165 DOI: 10.1186/s40169-018-0183-8] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2017] [Accepted: 01/21/2018] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Stromal vascular fraction (SVF) represents an attractive source of adult stem cells and progenitors, holding great promise for numerous cell therapy approaches. In 2017, it was reported that 1524 patients received autologous SVF following the enzymatic digestion of liposuction fat. The treatment was safe and effective and patients showed significant clinical improvement. In a collaborative study, we analyzed SVF obtained from 58 patients having degenerative, inflammatory, autoimmune diseases, and advanced stage cancer. RESULTS Flow analysis showed that freshly isolated SVF was very heterogeneous and harbored four major subsets specific to adipose tissue; CD34high CD45- CD31- CD146- adipose-derived stromal/stem cells (ADSCs), CD34low CD45+ CD206+CD31- CD146- hematopoietic stem cell-progenitors (HSC-progenitors), CD34high CD45- CD31+CD146+ adipose tissue-endothelial cells and CD45-CD34-CD31-CD146+ pericytes. Culturing and expanding of SVF revealed a homogenous population lacking hematopoietic lineage markers CD45 and CD34, but were positive for CD90, CD73, CD105, and CD44. Flow cytometry sorting of viable individual subpopulations revealed that ADSCs had the capacity to grow in adherent culture. The identity of the expanded cells as mesenchymal stem cells (MSCs) was further confirmed based on their differentiation into adipogenic and osteogenic lineages. To identify the potential factors, which may determine the beneficial outcome of treatment, we followed 44 patients post-SVF treatment. The gender, age, clinical condition, certain SVF-dose and route of injection, did not play a role on the clinical outcome. Interestingly, SVF yield seemed to be affected by patient's characteristic to various extents. Furthermore, the therapy with adipose-derived and expanded-mesenchymal stem cells (ADE-MSCs) on a limited number of patients, did not suggest increased efficacies compared to SVF treatment. Therefore, we tested the hypothesis that a certain combination, rather than individual subset of cells may play a role in determining the treatment efficacy and found that the combination of ADSCs to HSC-progenitor cells can be correlated with overall treatment efficacy. CONCLUSIONS We found that a 2:1 ratio of ADSCs to HSC-progenitors seems to be the key for a successful cell therapy. These findings open the way to future rational design of new treatment regimens for individuals by adjusting the cell ratio before the treatment.
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Affiliation(s)
- Mehmet Okyay Kilinc
- Department of Biochemistry, Biocenter, University of Wuerzburg, Am Hubland, 97070 Würzburg, Germany
- StemImmune Inc., San Diego, CA 92122 USA
| | | | | | | | | | | | - Elliot Lander
- Cell Surgical Network and California Stem Cell Treatment Center, Rancho Mirage, CA 92270 USA
| | - Mark Berman
- Cell Surgical Network and California Stem Cell Treatment Center, Rancho Mirage, CA 92270 USA
| | - Boris Minev
- StemImmune Inc., San Diego, CA 92122 USA
- Radiation Medicine, Moores Cancer Center, University of California San Diego, La Jolla, CA 92037 USA
| | - Aladar A. Szalay
- Department of Biochemistry, Biocenter, University of Wuerzburg, Am Hubland, 97070 Würzburg, Germany
- StemImmune Inc., San Diego, CA 92122 USA
- Radiation Medicine, Moores Cancer Center, University of California San Diego, La Jolla, CA 92037 USA
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Menzi N, Osinga R, Todorov A, Schaefer DJ, Martin I, Scherberich A. Wet milling of large quantities of human excision adipose tissue for the isolation of stromal vascular fraction cells. Cytotechnology 2018; 70:807-817. [PMID: 29344745 DOI: 10.1007/s10616-018-0190-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2017] [Accepted: 01/08/2018] [Indexed: 12/21/2022] Open
Abstract
The isolation of stromal vascular fraction (SVF) cells from excised human adipose tissue, for clinical or research purposes, implies the tedious and time consuming process of manual mincing prior to enzymatic digestion. Since no efficient alternative technique to this current standard procedure has been proposed so far, the aim of this study was to test a milling procedure, using two simple, inexpensive and commercially available manual meat grinders, to process large amounts of adipose tissue. The procedure was assessed on adipose tissue resections from seven human donors and compared to manual mincing with scalpels. The processed adipose tissues were digested and the resulting SVF cells compared in terms of number, clonogenicity and differentiation capacity. After 10 min of processing, either device tested yielded on average sixfold more processed material for subsequent cell isolation than manual mincing. The isolation yield of SVF cells (isolated cells per ml of adipose tissue), their viability, phenotype, clonogenicity and osteogenic/adipogenic differentiation capacity, tested by production of mineralized matrix and lipid vacuoles, respectively, were comparable. This new method is practical and inexpensive and represents an efficient alternative to the current standard for large scale adipose tissue resection processing. A device based on the milling principle could be embedded within a streamlined system for isolation and clinical use of SVF cells from adipose tissue excision.
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Affiliation(s)
- Nadia Menzi
- Department of Biomedicine, University Hospital Basel, University of Basel, Hebelstrasse 20, 4031, Basel, Switzerland.,Department of Plastic, Reconstructive, Aesthetic and Hand Surgery, University Hospital Basel, Spitalstrasse 21, 4031, Basel, Switzerland
| | - Rik Osinga
- Department of Biomedicine, University Hospital Basel, University of Basel, Hebelstrasse 20, 4031, Basel, Switzerland.,Department of Plastic, Reconstructive, Aesthetic and Hand Surgery, University Hospital Basel, Spitalstrasse 21, 4031, Basel, Switzerland
| | - Atanas Todorov
- Department of Biomedicine, University Hospital Basel, University of Basel, Hebelstrasse 20, 4031, Basel, Switzerland.,Department of Biomedical Engineering, University of Basel, Gewerbestrasse 14, 4123, Allschwil, Switzerland
| | - Dirk Johannes Schaefer
- Department of Plastic, Reconstructive, Aesthetic and Hand Surgery, University Hospital Basel, Spitalstrasse 21, 4031, Basel, Switzerland
| | - Ivan Martin
- Department of Biomedicine, University Hospital Basel, University of Basel, Hebelstrasse 20, 4031, Basel, Switzerland. .,Department of Biomedical Engineering, University of Basel, Gewerbestrasse 14, 4123, Allschwil, Switzerland.
| | - Arnaud Scherberich
- Department of Biomedicine, University Hospital Basel, University of Basel, Hebelstrasse 20, 4031, Basel, Switzerland.,Department of Plastic, Reconstructive, Aesthetic and Hand Surgery, University Hospital Basel, Spitalstrasse 21, 4031, Basel, Switzerland.,Department of Biomedical Engineering, University of Basel, Gewerbestrasse 14, 4123, Allschwil, Switzerland
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Caggiati A, Germani A, Di Carlo A, Borsellino G, Capogrossi MC, Picozza M. Naturally Adipose Stromal Cell-Enriched Fat Graft: Comparative Polychromatic Flow Cytometry Study of Fat Harvested by Barbed or Blunt Multihole Cannula. Aesthet Surg J 2017; 37:591-602. [PMID: 28052909 DOI: 10.1093/asj/sjw211] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Background Fat grafts enriched with cells of the stromal vascular fraction (SVF), especially adipose-derived stromal cells (ASCs), exhibit significantly improved retention over non enriched, plain fat. Different types of liposuction cannulae may yield lipoaspirates with different subpopulations of cells. Moreover, preparation of adipose tissue for transplantation typically involves centrifugation, which creates a density gradient of fat. Objectives The authors sought to determine whether liposuction with a barbed or smooth cannula altered the enrichment of the SVF, and specifically ASCs, in low-density (LD) and high-density (HD) fractions of centrifuged adipose tissue. Methods Fat was harvested from 2 abdominal sites of 5 healthy women with a barbed or smooth multihole blunt-end cannula. After centrifugation, LD and HD fat fractions were digested with collagenase and analyzed by polychromatic flow cytometry to identify and enumerate distinct populations of cells. Results Overall cell yield and the number of immune cells were consistently higher in HD fractions than in LD fractions, regardless of the cannula employed. More living cells, and specifically more ASCs, populated the HD fractions of lipoaspirates obtained with a barbed cannula than with a smooth cannula. Conclusions In this study, lipoaspiration with a barbed cannula and isolation of the HD layer of centrifuged adipose tissue yielded maximal amounts of SVF cells, including ASCs.
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Affiliation(s)
- Alessio Caggiati
- Director of the Plastic Surgery Unit, Istituto Dermopatico dell'Immacolata-IRCCS-FLMM, Rome, Italy
| | - Antonia Germani
- Consultant, Istituto Dermopatico dell'Immacolata-IRCCS Scientific Board, Rome, Italy
| | - Anna Di Carlo
- Research Fellow, Laboratory of Vascular Pathology, Istituto Dermopatico dell'Immacolata-IRCCS, Rome, Italy
| | - Giovanna Borsellino
- Research Associate, Neuroimmunology and Flow Cytometry Units, Santa Lucia Foundation, Rome, Italy
| | - Maurizio C Capogrossi
- Head, Laboratory of Vascular Pathology, Istituto Dermopatico dell'Immacolata-IRCCS, Rome, Italy
| | - Mario Picozza
- Research Fellow, Laboratory of Vascular Pathology, Istituto Dermopatico dell'Immacolata-IRCCS, Rome, Italy
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Hanke A, Prantl L, Wenzel C, Nerlich M, Brockhoff G, Loibl M, Gehmert S. Semi-automated extraction and characterization of Stromal Vascular Fraction using a new medical device. Clin Hemorheol Microcirc 2017; 64:403-412. [PMID: 27886006 DOI: 10.3233/ch-168124] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
INTRODUCTION The stem cell rich Stromal Vascular Fraction (SVF) can be harvested by processing lipo-aspirate or fat tissue with an enzymatic digestion followed by centrifugation. To date neither a standardised extraction method for SVF nor a generally admitted protocol for cell application in patients exists. A novel commercially available semi-automated device for the extraction of SVF promises sterility, consistent results and usability in the clinical routine. The aim of this work was to compare the quantity and quality of the SVF between the new system and an established manual laboratory method. MATERIAL AND METHODS SVF was extracted from lipo-aspirate both by a prototype of the semi-automated UNiStation™ (NeoGenesis, Seoul, Korea) and by hand preparation with common laboratory equipment. Cell composition of the SVF was characterized by multi-parametric flow-cytometry (FACSCanto-II, BD Biosciences). The total cell number (quantity) of the SVF was determined as well the percentage of cells expressing the stem cell marker CD34, the leucocyte marker CD45 and the marker CD271 for highly proliferative stem cells (quality). RESULTS Lipo-aspirate obtained from six patients was processed with both the novel device (d) and the hand preparation (h) which always resulted in a macroscopically visible SVF. However, there was a tendency of a fewer cell yield per gram of used lipo-aspirate with the device (d: 1.1×105±1.1×105 vs. h: 2.0×105±1.7×105; p = 0.06). Noteworthy, the percentage of CD34+ cells was significantly lower when using the device (d: 57.3% ±23.8% vs. h: 74.1% ±13.4%; p = 0.02) and CD45+ leukocyte counts tend to be higher when compared to the hand preparation (d: 20.7% ±15.8% vs. h: 9.8% ±7.1%; p = 0.07). The percentage of highly proliferative CD271+ cells was similar for both methods (d:12.9% ±9.6% vs. h: 13.4% ±11.6%; p = 0.74) and no differences were found for double positive cells of CD34+/CD45+ (d: 5.9% ±1.7% vs. h: 1.7% ±1.1%; p = 0.13), CD34+/CD271+ (d: 24.1% ±12.0% vs. h: 14.2% ±8.5%; p = 0.07). DISCUSSION The semi-automated closed system provides a considerable amount of sterile SVF with high reproducibility. Furthermore, the SVF extracted by both methods showed a similar cell composition which is in accordance with the data from literature. This semi-automated device offers an opportunity to take research and application of the SVF one step further to the clinic.
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Affiliation(s)
- Alexander Hanke
- Department of Plastic Surgery, University Medical Center Regensburg, Germany.,Applied Stem Cell Research Center, University Medical Center Regensburg, Germany
| | - Lukas Prantl
- Department of Plastic Surgery, University Medical Center Regensburg, Germany.,Applied Stem Cell Research Center, University Medical Center Regensburg, Germany
| | - Carina Wenzel
- Department of Plastic Surgery, University Medical Center Regensburg, Germany.,Applied Stem Cell Research Center, University Medical Center Regensburg, Germany
| | - Michael Nerlich
- Department of Trauma Surgery, University Medical Center Regensburg, Germany
| | - Gero Brockhoff
- Department of Obstetrics and Gynecology, University Medical Center Regensburg, Regensburg, Germany
| | - Markus Loibl
- Applied Stem Cell Research Center, University Medical Center Regensburg, Germany.,Department of Trauma Surgery, University Medical Center Regensburg, Germany
| | - Sebastian Gehmert
- Applied Stem Cell Research Center, University Medical Center Regensburg, Germany.,Department of Orthopaedics and Trauma Surgery, University Hospital Basel, Switzerland
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McFarlin BK, Carpenter KC, Henning AL, Venable AS. Consumption of a high-fat breakfast on consecutive days alters preclinical biomarkers for atherosclerosis. Eur J Clin Nutr 2016; 71:239-244. [PMID: 28000693 DOI: 10.1038/ejcn.2016.242] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2016] [Revised: 08/11/2016] [Accepted: 09/13/2016] [Indexed: 12/30/2022]
Abstract
BACKGROUND/OBJECTIVES Recent research has speculated that the risk of developing atherosclerosis is due to the accumulation of the effects of daily diet choices. The purpose of this study was to examine which of our previously identified preclinical disease risk biomarkers were further elevated when consuming a high-fat (644±50 kcal; 100% recommended dietary allowance for fat), high-calorie (1118±100 kcal; 70% daily caloric needs) breakfast on consecutive days. Young, normal weight females (N=7) participated in this study. SUBJECTS/METHODS Blood samples were taken premeal and hourly for 5-h postprandial. Serum biomarkers (C-peptide, eotaxin, gastric inhibitory polypeptide, granulocyte colony-stimulating factor (G-CSF), granulocyte-monocyte colony-stimulating factor (GM-CSF), insulin, leptin, monocyte chemoattractant protein 1, pancreatic polypeptide (PPY) and tumor necrosis factor-α), monocyte concentration, and adhesion molecule expression (CD11a, CD18 and CD54) were measured. Area under the curve was calculated for each outcome variable as a function of day and data were analyzed for significance. RESULTS We found significant (P<0.05) increases on Day 2 for: GM-CSF (+47%; P=0.041), G-CSF (+31%; P=0.012), PPY (+51%; P=0.049), total monocyte (+110%; P=0.043), pro-inflammatory (PI) monocyte (+60%; P=0.012), PI monocyte CD18 (+960%; P=0.003), PI monocyte CD11a (+230%; P=0.006), and PI monocyte CD54 (+208%; P=0.015). CONCLUSIONS To our knowledge, the present study is the first to report changes in selected biomarkers and monocytes following eating a high-fat, high-calorie breakfast on consecutive days in humans. More research is needed to determine how transient the observed changes are and what the long-term implications for disease risk are.
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Affiliation(s)
- B K McFarlin
- Applied Physiology Laboratory, University of North Texas, Denton, TX, USA.,Department of Biological Sciences, University of North Texas, Denton, TX, USA
| | - K C Carpenter
- Native American Community Health Center, Inc., Phoenix, AZ, USA
| | - A L Henning
- Applied Physiology Laboratory, University of North Texas, Denton, TX, USA.,Department of Biological Sciences, University of North Texas, Denton, TX, USA
| | - A S Venable
- Applied Physiology Laboratory, University of North Texas, Denton, TX, USA.,Department of Biological Sciences, University of North Texas, Denton, TX, USA
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Shift toward Mechanical Isolation of Adipose-derived Stromal Vascular Fraction: Review of Upcoming Techniques. PLASTIC AND RECONSTRUCTIVE SURGERY-GLOBAL OPEN 2016; 4:e1017. [PMID: 27757339 PMCID: PMC5055005 DOI: 10.1097/gox.0000000000001017] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2016] [Accepted: 07/05/2016] [Indexed: 12/28/2022]
Abstract
Standard isolation of adipose stromal vascular fraction (SVF) requires the use of collagenase and is considered more than “minimally manipulated” by current good manufacturing practice requirements. Alternatively, nonenzymatic isolation methods have surfaced using physical forces to separate cells from the adipose matrix. The purpose of this study was to review the literature on the use of mechanical isolation protocols and compare the results. The implication for use as a standard procedure in practice is discussed.
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23
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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]
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Cell-Assisted Skin Grafting: Improving Texture and Elasticity of Skin Grafts through Autologous Cell Transplantation. Plast Reconstr Surg 2016; 137:58e-66e. [PMID: 26710061 DOI: 10.1097/prs.0000000000001949] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND Full-thickness skin grafts are widely used in plastic and reconstructive surgery. Their poor textural durability and associated contracture make them less desirable than skin flaps. Currently, stromal vascular fraction cells hold great promise because of their angiogenic potential, which may ameliorate the hypoxic period after skin grafting. In this study, autologous transplantation of stromal vascular fraction cells was used in combination with skin grafts to determine whether it improved the texture and other physical property of skin grafts. METHODS Stromal vascular fraction cells were isolated and injected under full-thickness skin grafts in a cohort of 20 rats; a second cohort of 20 rats served as controls. Skin grafts were harvested and analyzed on days 14, 30, and 90 after injections. Bioluminescent imaging with luciferase-stromal vascular fraction cells was used for cell tracing. Contracture ratios, elasticity modulus, and the stiffness of each graft were evaluated. Angiogenesis was evaluated using immunohistochemical techniques against vascular endothelial growth factor. Blood flow signals of the graft were also measured, and expression of vascular endothelial growth factor, hepatocyte growth factor, and basic fibroblast growth factor was assessed in all grafts. RESULTS Stromal vascular fraction cells markedly decreased the contracture of skin grafts and improved their resilience and elasticity after 1 month. Histologically, the cells enhanced skin thickness and skin vascularization. Moreover, expression of vascular endothelial growth factor, basic fibroblast growth factor, and hepatocyte growth factor also increased in the stromal vascular fraction group. CONCLUSION Autologous stromal vascular fraction cell transplantation enhances angiogenesis after skin grafting and improves the texture and elasticity of skin grafts.
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25
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Guillaume-Jugnot P, Daumas A, Magalon J, Sautereau N, Veran J, Magalon G, Sabatier F, Granel B. State of the art. Autologous fat graft and adipose tissue-derived stromal vascular fraction injection for hand therapy in systemic sclerosis patients. Curr Res Transl Med 2016; 64:35-42. [PMID: 27140597 DOI: 10.1016/j.retram.2016.01.006] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2015] [Accepted: 01/04/2016] [Indexed: 01/27/2023]
Abstract
Systemic sclerosis is an autoimmune disease characterized by sclerosis (hardening) of the skin and deep viscera associated with microvascular functional and structural alteration, which leads to chronic ischemia. In the hands of patients, ischemic and fibrotic damages lead to both pain and functional impairment. Hand disability creates a large burden in professional and daily activities, with social and psychological consequences. Currently, the proposed therapeutic options for hands rely mainly on hygienic measures, vasodilatator drugs and physiotherapy, but have many constraints and limited effects. Developing an innovative therapeutic approach is crucial to reduce symptoms and improve the quality of life. The discovery of adult stem cells from adipose tissue has increased the interest to use adipose tissue in plastic and regenerative surgery. Prepared as freshly isolated cells for immediate autologous transplantation, adipose tissue-derived stem cell therapy has emerged as a therapeutic alternative for the regeneration and repair of damaged tissues. We aim to update literature in the interest of autologous fat graft or adipose derived from stromal vascular fraction cell-based therapy for the hands of patients who suffer from systemic sclerosis.
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Affiliation(s)
- P Guillaume-Jugnot
- Service de médecine interne, hôpital Nord, Assistance publique-Hôpitaux de Marseille (AP-HM), 13915 Marseille cedex 05, France
| | - A Daumas
- Service de médecine interne, gériatrie et thérapeutique, hôpital de la Timone, AP-HM, 13385 Marseille cedex 05, France
| | - J Magalon
- Laboratoire de culture et thérapie cellulaire, Inserm CBT-1409, hôpital de la Conception, AP-HM, 13385 Marseille cedex 05, France
| | - N Sautereau
- Service de médecine interne, hôpital Nord, Assistance publique-Hôpitaux de Marseille (AP-HM), 13915 Marseille cedex 05, France
| | - J Veran
- Laboratoire de culture et thérapie cellulaire, Inserm CBT-1409, hôpital de la Conception, AP-HM, 13385 Marseille cedex 05, France
| | - G Magalon
- Service de chirurgie plastique et réparatrice, hôpital de la Conception, AP-HM, 13385 Marseille cedex 05, France
| | - F Sabatier
- Laboratoire de culture et thérapie cellulaire, Inserm CBT-1409, hôpital de la Conception, AP-HM, 13385 Marseille cedex 05, France; Inserm UMR 1076 Vascular Research Centre of Marseille, Aix-Marseille université, 13385 Marseille cedex 05, France
| | - B Granel
- Service de médecine interne, hôpital Nord, Assistance publique-Hôpitaux de Marseille (AP-HM), 13915 Marseille cedex 05, France; Inserm UMR 1076 Vascular Research Centre of Marseille, Aix-Marseille université, 13385 Marseille cedex 05, France.
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Navarro A, Marín S, Riol N, Carbonell-Uberos F, Miñana MD. Fibroblast-Negative CD34-Negative Cells from Human Adipose Tissue Contain Mesodermal Precursors for Endothelial and Mesenchymal Cells. Stem Cells Dev 2015; 24:2280-96. [DOI: 10.1089/scd.2015.0013] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023] Open
Affiliation(s)
- Amparo Navarro
- Regenerative Medicine Laboratory, Fundación Hospital General Universitario, Valencia, Spain
| | - Severiano Marín
- Department of Plastic and Reconstructive Surgery, Consorcio Hospital General Universitario, Valencia, Spain
| | - Nicasia Riol
- Immunohematology Service, Centro de Transfusiones, Valencia, Spain
| | | | - María Dolores Miñana
- Regenerative Medicine Laboratory, Fundación Hospital General Universitario, Valencia, Spain
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Li M, Zhang G, Zhang X, Lv G, Wei X, Yuan H, Hou J. Overexpression of B7-H3 in CD14+ monocytes is associated with renal cell carcinoma progression. Med Oncol 2014; 31:349. [DOI: 10.1007/s12032-014-0349-1] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2014] [Accepted: 11/11/2014] [Indexed: 10/24/2022]
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