Mesenchymal stem cell dysfunction in diabetes

Fijany, Arman; Sayadi, Lohrasb; Khoshab, Nima; Banyard, Derek A.; Shaterian, Ashkaun; Alexander, Michael P.; Lakey, Johnathan R T; Paydar, Keyianoosh Z.; Evans, Gregory R. D.; Widgerow, Alan D.

doi:10.1007/s11033-018-4516-x

Cited by 52 publications

(34 citation statements)

References 110 publications

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“…from the removal of adipose tissue to implant during production and/or transport. It should be stressed, however, that ASCs from patients with inflammatory diseases display functional abnormalities and lower inflammatory capacities . Furthermore, it seems important to define the fistulous disease to be treated.…”

Section: Discussionmentioning

confidence: 99%

Autologous adipose-derived stem cells for the treatment of complex cryptoglandular perianal fistula: A randomized clinical trial with long-term follow-up

García‐Arranz

García-Olmo

Herreros

et al. 2019

Stem Cells Translational Medicine

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The aim of this clinical trial (ID Number NCT01803347) was to determine the safety and efficacy of autologous adipose‐derived stem cells (ASCs) for treatment of cryptoglandular fistula. This research was conducted following an analysis of the mistakes of a same previous phase III clinical trial. We designed a multicenter, randomized, single‐blind clinical trial, recruiting 57 patients. Forty‐four patients were categorized as belonging to the intent‐to‐treat group. Of these, 23 patients received 100 million ASCs plus intralesional fibrin glue (group A) and 21 received intralesional fibrin glue (group B), both after a deeper curettage of tracks and closure of internal openings. Fistula healing was defined as complete re‐epithelialization of external openings. Those patients in whom the fistula had not healed after 16 weeks were eligible for retreatment. Patients were evaluated at 1, 4, 16, 36, and 52 weeks and 2 years after treatment. Results were assessed by an evaluator blinded to the type of treatment. After 16 weeks, the healing rate was 30.4% in group A and 42.8% in group B, rising to 55.0% and 63.1%, respectively, at 52 weeks. At the end of the study (2 years after treatment), the healing rate remained at 50.0% in group A and had reduced to 26.3% in group B. The safety of the cellular treatment was confirmed and no impact on fecal continence was detected. The main conclusion was that autologous ASCs for the treatment of cryptoglandular perianal fistula is safe and can favor long‐term and sustained fistula healing.

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Section: Discussionmentioning

confidence: 99%

Autologous adipose-derived stem cells for the treatment of complex cryptoglandular perianal fistula: A randomized clinical trial with long-term follow-up

García‐Arranz

García-Olmo

Herreros

et al. 2019

Stem Cells Translational Medicine

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“…Changes in systemic and local microenvironment, like those of diabetes mellitus, may compromise MSC intrinsic functions. Indeed, insulin resistance, hyperglycemia, persistent inflammation, increased oxidative stress, and the accumulation of advanced glycation end products affect proliferation, differentiation, angiogenic capability, and cytokine secretion of MSCs from bone marrow and subcutaneous adipose tissue (Fijany et al, 2019; van de Vyver, 2017). The effect of metabolic derangements on BFP–MSCs, however, has never been explored.…”

Section: Introductionmentioning

confidence: 99%

Platelet‐rich plasma counteracts detrimental effect of high‐glucose concentrations on mesenchymal stem cells from Bichat fat pad

D’Esposito

Lecce

Marenzi

et al. 2020

J Tissue Eng Regen Med

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Diabetic patients display increased risk of periodontitis and failure in bone augmentation procedures. Mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP) represent a relevant advantage in tissue repair process and regenerative medicine. We isolated MSCs from Bichat's buccal fat pad (BFP) and measured the effects of glucose and PRP on cell number and osteogenic differentiation potential. Cells were cultured in the presence of 5.5-mM glucose (low glucose [LG]) or 25-mM glucose (high glucose [HG]). BFP-MSC number was significantly lower when cells were cultured in HG compared with those in LG. Following osteogenic differentiation procedures, calcium accumulation, alkaline phosphatase activity, and expression of osteogenic markers were significantly lower in HG compared with LG. Exposure of BFP-MSC to PRP significantly increased cell number and osteogenic differentiation potential, reaching comparable levels in LG and in HG. Thus, high-glucose concentrations impair BFP-MSC growth and osteogenic differentiation. However, these detrimental effects are largely counteracted by PRP. K E Y W O R D S Bichat's buccal fat pad, bone reconstruction, diabetes, mesenchymal stem cells, platelet-rich plasma Vittoria D'Esposito and Manuela Lecce equally contributed to this work.

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“…However, high concentration of glucose may promote the expression level of PPAR-γ and C/EBP-α in the cells of MSCs to differentiate into adipocytes and osteoblasts [47,48]. When using autologous MSC for cell therapy, MSCs function deteriorates as patients age [49,50], and complications related to diabetic MSCs dysfunction contribute to the major pathological changes seen in the growing diabetic population [51]. However, the use of allogeneic MSC therapy also has problems such as short survival time [52] and gene contamination of others.…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal stem cells modified by FGF21 and GLP1 ameliorate lipid metabolism while reducing blood glucose in type 2 diabetic mice

Xue¹,

Xiao

Yu³

et al. 2020

Preprint

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Objective: The purpose of the study was to investigate the therapeutic effects and safety of genetic modified mesenchymal stem cells (MSCs) in type 2 diabetes mellitues (T2DM).Methods: MSCs derived from adipose tissue were modified with over-expression of FGF21 and GLP1, which was achieved through lentiviral particles transduction. The cells were transplanted to the BKS.Cg-Dock7m+/+Leprdb/Nju mice (T2DM mice model). The injections of physiological saline (0.1 mL), Liraglutide (0.5mg/kg) were employed as negative and positive controls respectively. The protein analyses were performed using ELISA or western blot analysis, while quantitative real-time PCR was adopted for gene expression.Results: The genetic modification had no effects on morphology, differentiation ability, or immunophenotype of MSCs. Moreover, MSC-FGF21+GLP1 cells exhibited significantly increased expression of FGF21 and GLP1. In T2DM model mice, the transplantation of MSC-FGF21+GLP1 cells ameliorated blood glucose and weight, promoted the secretion of insulin, enhanced the recovery of liver structures, and improved lipid profiles. Moreover, FGF21 and GLP1 exhibited synergistic effects in regulation of glucolipid metabolism through controlling the expression of insulin, srebp1 and srebp2.Conclusion: The stem cell treatment based on MSCs modified by FGF21 and GLP1 genes is an effective approach for treatment of T2DM.

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Mesenchymal stem cell dysfunction in diabetes

Cited by 52 publications

References 110 publications

Autologous adipose-derived stem cells for the treatment of complex cryptoglandular perianal fistula: A randomized clinical trial with long-term follow-up

Autologous adipose-derived stem cells for the treatment of complex cryptoglandular perianal fistula: A randomized clinical trial with long-term follow-up

Platelet‐rich plasma counteracts detrimental effect of high‐glucose concentrations on mesenchymal stem cells from Bichat fat pad

Mesenchymal stem cells modified by FGF21 and GLP1 ameliorate lipid metabolism while reducing blood glucose in type 2 diabetic mice

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