Differentiation of adipose-derived stem cells into functional islet-like cells using Conophlline and Nicotinamide

doi:10.3969/j.issn.2095-4344.2013.06.013

Abstract

Abstract:

BACKGROUND: Allogenic islet transplantation for type 1 diabetes is limited by shortage of donor islet cells and immune suppression, bioengineered islet-like clusters developed from autogenic stem cells might benefit diabetic patients by immunorejection free and off-shelf cellular treatment.
OBJECTIVE: To investigate whether adipose tissue from adults have the potential to differentiate into insulin secreting, glucose responsive, functional islet-like clusters and to develop a practical approach for islet bioengineering in vitro.
METHODS: Human adipose stem cells were isolated, cultured and expanded from human subcutaneous adipose tissue. Conophylline, a new plant derived inducer, in combination with other factors were used to induce human adipose stem cells into islet-like clusters and their efficiencies for islet-like clusters generation were compared. Differentiated cells were identified by tissue specific surface marker staining, reverse transcription-PCR and immunocytochemistry at protein and mRNA level. Finally, insulin secretion of cell clusters in different glucose concentrations was tested with enzyme-linked immunosorbent assay.
RESULTS AND CONCLUSION: Multipotential adipose stem cells were cultured and expanded from adult subcutaneous adipose tissues. Those stem cells were conveniently differentiated into glucose responsive and insulin-secreting functional islet-like clusters. Conophylline in combination with Nicotinamide have the best efficiency of differentiating human adipose stem cells into islet cells.

Key words: stem cells, adipose-derived stem cells, nicotinamide, conophlline, adipose-derived stem cells, islet-like cells, diabetes, insulin, differentiation, efficient induction, islet differentiation, stem cell photographs-containing paper

CLC Number:

R394.2

Yang Ping, Zheng Qin-long, Wang Jin-feng, Huang Jia-xue. Differentiation of adipose-derived stem cells into functional islet-like cells using Conophlline and Nicotinamide[J]. Chinese Journal of Tissue Engineering Research, 2013, 17(6): 1024-1028.

Figures/Tables 5

References

[1] Vija L, Farge D, Gautier JF, et al. Mesenchymal stem cells: Stem cell therapy perspectives for type 1 diabetes. Diabetes＆Metabolism. 2009;35(2):85-93.

[2] Shapiro AM, Lakey JR, Ryan EA, et al. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid free immunosuppressive regimen. N Engl J Med. 2000;343(4):230-238.

[3] Shapiro AM, Ricordi C, Hering BJ, et al. International trial of the Edmonton protocol for islet transplantation. N Engl J Med. 2006;355(13):1318-1330.

[4] Zuk PA, Zhu M, MizunoH, et al. Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng. 2001;7(2):211-228.

[5] Zuk PA, Zhu M, Ashjian P, et al. Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell. 2002;13(12): 4279-4295.

[6] Schaffler A, Buchler C. Concise review: Adipose tissue-derived stromal cells-basic and clinical implications for novel cell-based therapies. Stem Cells. 2007;25(4):818-827.

[7] Timper K, Seboek D, Eberhardt M, et al. Human adipose tissue-derived mesenchymal stem cells differentiate into insulin, somatostatin,and glucagon expressing cells. Biochem Biophys Res Commun. 2006;341(4):1135-1140.

[8] Dubois SG, Floyd EZ, Zvonic S, et al. Isolation of Human Adipose-derived Stem Cells from Biopsies and Liposuction Specimens. Methods in Molecular Biology. 2008;449:69-79.

[9] Hisanaga E, Park KY, Yamada S, et a1. A simple method to induce differentiation of murine bone marrow mesenchymal cells to insulin-producing cells using conophylline and betacellulin-delta4. Endocrine Journal. 2008;55(3):535-543.

[10] Li HD, Wei J, Mu CZ. Chinese Bulletin of Life Sciences. 2007; 19(4):401-408. 李宏丹,魏嘉,穆长征. 1型糖尿病的干细胞治疗研究进展[J]. 生命科学,2007,19(4):401-408.

[11] Lee J, Han DJ, Kim SC. In vitro differentiation of human adipose tissue-derived stem cells into cells with pancreatic phenotype by regenerating pancreas extract. Biochemical and Biophysical Reseach Communications. 2008;375(4): 547-551.

[12] Ogata T, Li L, Yamada S, et al. Promotion of betacell differentiation by conophylline in fetal and neonatalrat pancreas. Diabetes. 2004;53(10):2596-2602.

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