Allogeneic Transplantation of an Adipose-Derived Stem Cell Sheet Combined With Artificial Skin Accelerates Wound Healing in a Rat Wound Model of Type 2 Diabetes and Obesity

Bone tissue regeneration is considered to be the optimal solution for bone loss. However, diabetic patients have a greater risk of poor bone healing or bone grafting failure than nondiabetics. The purpose of this study was to investigate the influence of the complexes of an adipose-derived stem cell sheet (ASC sheet) and Bio-Oss® bone granules on bone healing in type 2 diabetes mellitus (T2DM) rats with the addition of semaphorin 3A (Sema3A). The rat ASC sheets showed stronger osteogenic ability than ASCs in vitro, as indicated by the extracellular matrix mineralization and the expression of osteogenesis-related genes at mRNA level. An ASC sheet combined with Bio-Oss® bone granules promoted bone formation in T2DM rats as indicated by microcomputed tomography (micro-CT) and histological analysis. In addition, Sema3A promoted the osteogenic differentiation of ASC sheets in vitro and local injection of Sema3A promoted T2DM rats’ calvarial bone regeneration based on ASC sheet and Bio-Oss® bone granule complex treatment. In conclusion, the local injection of Sema3A and the complexes of ASC sheet and Bio-Oss® bone granules could promote osseous healing and are potentially useful to improve bone healing for T2DM patients.

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Semaphorin 3A-modified adipose-derived stem cell sheet may improve osseointegration in a type 2 diabetes mellitus rat model

Molecular Medicine Reports ◽

10.3892/mmr.2016.5568 ◽

2016 ◽

Vol 14 (3) ◽

pp. 2449-2456 ◽

Cited By ~ 6

Author(s):

Kaixiu Fang ◽

Wen Song ◽

Lifeng Wang ◽

Xiaoru Xu ◽

Naiwen Tan ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Stem Cell ◽

Rat Model ◽

Cell Sheet ◽

Semaphorin 3A ◽

Adipose Derived Stem Cell

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ID: 1014 Expanded autologous adipose derived stem cell transplantation for type 2 diabetes mellitus

Biomedical Research and Therapy ◽

10.15419/bmrat.v4is.292 ◽

2017 ◽

Vol 4 (S) ◽

pp. 88

Author(s):

Phuong Thi-Bich Le ◽

Phuc Van Pham ◽

Ngoc Bich Vu ◽

Loan Thi-Tung Dang ◽

Ngoc Kim Phan

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Stem Cell ◽

Blood Glucose ◽

Blood Glucose Level ◽

Glucose Level ◽

Therapeutic Effects ◽

Adipose Derived Stem Cell

Introduction: Type 2 diabetes mellitus (T2D) is the most common form of diabetes mellitus, accounting for 90% of diabetes mellitus in patients. At the present time, although T2D can be treated by various drugs and therapies using insulin replacement, reports have shown that complications including microvascular, macrovascular complications and therapy resistance can occur in patients on long term treatment. Stem cell therapy is regarded as a promising therapy for diabetes mellitus, including T2D. The aim of this study was to evaluate the safety and therapeutic effect of expanded autologous adipose derived stem cell (ADSC) transplantation for T2D treatment; the pilot study included 3 patients who were followed for 3 months. Methods: The ADSCs were isolated from stromal vascular fractions, harvested from the belly of the patient,and expanded for 21 days per previously published studies. Before transplantation, ADSCs were evaluated for endotoxin, mycoplasma contamination, and karyotype. All patients were transfused with ADSCs at 1-2x106 cells/kg of body weight.Patients were evaluated for criteria related to transplantation safety and therapeutic effects; these included fever, blood glucose level before transplantation of ADSCs, and blood glucose level after transplantation (at 1, 2 and 3 months). Results: The results showed that all samples of ADSCs exhibited the MSC phenotype with stable karyotype (2n=46), there was no contamination of mycoplasma, and endotoxin levels were low (<0.25 EU/mL). No adverse effects were detected after 3 months of transplantation. Decreases of blood glucose levels were recorded in all patients. Conclusion: The findings from this initial study show that expanded autologous ADSCs may be a promising treatment for T2D.

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KGF-2 and FGF-21 poloxamer 407 hydrogel coordinates inflammation and proliferation homeostasis to enhance wound repair of scalded skin in diabetic rats

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2019-001009 ◽

2020 ◽

Vol 8 (1) ◽

pp. e001009 ◽

Cited By ~ 2

Author(s):

Xuanxin Yang ◽

Rongshuai Yang ◽

Min Chen ◽

Qingde Zhou ◽

Yingying Zheng ◽

...

Keyword(s):

Type 2 Diabetes ◽

Wound Healing ◽

Growth Factor ◽

Granulation Tissue ◽

Inflammatory Responses ◽

Poloxamer 407 ◽

Thermosensitive Hydrogel ◽

Gk Rats ◽

Wound Model

ObjectiveThe present study focused on the development of a poloxamer 407 thermosensitive hydrogel loaded with keratinocyte growth factor-2 (KGF-2) and fibroblast growth factor-21 (FGF-21) as a therapeutic biomaterial in a scald-wound model of type-2 diabetes in Goto-Kakizaki (GK) rats.Research design and methodsIn this study, a poloxamer 407 thermosensitive hydrogel loaded with KGF-2 and/or FGF-21 was prepared and its physical and biological properties were characterized. The repairing effects of this hydrogel were investigated in a scald-wound model of type-2 diabetes in GK rats. The wound healing rate, epithelialization, and formation of granulation tissue were examined, and biomarkers reflecting regulation of proliferation and inflammation were quantified by immunostaining and Western blotting. T tests and analyses of variance were used for statistical analysis via Graphpad Prism V.6.0.ResultsA 17.0% (w/w) poloxamer 407 combined with 1.0% (w/w) glycerol exhibited controlled release characteristics and a three-dimensional structure. A KGF-2/FGF-21 poloxamer hydrogel promoted cellular migration without apoptosis. This KGF-2/FGF-21 poloxamer hydrogel also accelerated wound healing of scalded skin in GK rats better than that of a KGF-2 or FGF-21 hydrogel alone due to accelerated epithelialization, formation of granulation tissue, collagen synthesis, and angiogenesis via inhibition of inflammatory responses and increased expression of alpha-smooth muscle actin (α-SMA), collagen III, pan-keratin, transforming growth factor-β (TGF-β), vascular endothelial growth factor (VEGF), and CD31.ConclusionsA KGF-2/FGF-21 poloxamer hydrogel accelerated wound healing of scalded skin in GK rats, which was attributed to a synergistic effect of KGF-2-mediated cellular proliferation and FGF-21-mediated inhibition of inflammatory responses. Taken together, our findings provide a novel and potentially important insight into improving wound healing in patients with diabetic ulcers.

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Dyslipidemia Is a Major Factor in Stem Cell Damage Induced by Uncontrolled Long-Term Type 2 Diabetes and Obesity in the Rat, as Suggested by the Effects on Stem Cell Culture

Journal of Sexual Medicine ◽

10.1016/j.jsxm.2018.09.019 ◽

2018 ◽

Vol 15 (12) ◽

pp. 1678-1697 ◽

Cited By ~ 6

Author(s):

Maryam Masouminia ◽

Robert Gelfand ◽

Istvan Kovanecz ◽

Dolores Vernet ◽

James Tsao ◽

...

Keyword(s):

Type 2 Diabetes ◽

Cell Culture ◽

Stem Cell ◽

Cell Damage ◽

Stem Cell Culture ◽

Diabetes And Obesity ◽

Term Type

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Expanded autologous adipose derived stem cell transplantation for type 2 diabetes mellitus

Biomedical Research and Therapy ◽

10.15419/bmrat.v3i12.141 ◽

2016 ◽

Vol 3 (12) ◽

pp. 1034 ◽

Cited By ~ 2

Author(s):

Phuong Thi-Bich Le ◽

Phuc Van Pham ◽

Ngoc Bich Vu ◽

Loan Thi-Tung Dang ◽

Ngoc Kim Phan

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Stem Cell ◽

Blood Glucose ◽

Blood Glucose Level ◽

Glucose Level ◽

Therapeutic Effects ◽

Adipose Derived Stem Cell

Introduction: Type 2 diabetes mellitus (T2D) is the most common form of diabetes mellitus, accounting for 90% of diabetes mellitus in patients. At the present time, althoughT2D can be treated by various drugs and therapies using insulin replacement, reports have shown that complications including microvascular, macrovascular complications and therapy resistance can occur in patients on long term treatment. Stem cell therapy is regarded as a promising therapy for diabetes mellitus, including T2D. The aim of this study was to evaluate the safety and therapeutic effect of expanded autologous adipose derived stem cell (ADSC) transplantation for T2D treatment; the pilot study included 3 patients who were followed for 3 months. Methods: The ADSCs were isolated from stromal vascular fractions, harvested from the belly of the patient,and expanded for 21 days per previously published studies. Before transplantation, ADSCs were evaluated for endotoxin, mycoplasma contamination, and karyotype.All patients were transfused with ADSCs at 1-2x106 cells/kg of body weight.Patients were evaluated for criteria related to transplantation safety and therapeutic effects; these included fever, blood glucose level before transplantation of ADSCs, and blood glucose level after transplantation (at 1, 2 and 3 months).Results: The results showed that all samples of ADSCs exhibited the MSC phenotype with stable karyotype (2n=46), there was no contamination of mycoplasma, and endotoxin levels were low (0.25 EU/mL). No adverse effects were detected after 3 months of transplantation. Decreases of blood glucose levels were recorded in all patients. Conclusion: The findings from this initial study show that expanded autologous ADSCs may be a promising treatment for T2D.

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