Human adipose tissue-derived mesenchymal stem cells differentiate into insulin, somatostatin, and glucagon expressing cells

Timper, Katharina; Seboek, Dalma; Eberhardt, Michael; Linscheid, Philippe; Christ‐Crain, Mirjam; Keller, Ulrich; Müller, Beat; Zulewski, Henryk

doi:10.1016/j.bbrc.2006.01.072

Cited by 397 publications

(281 citation statements)

References 32 publications

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“…In our study the transdifferentiation of h-AD-MSCs into IS-MSC with the ability to secrete insulin and C-peptide in response to glucose, were confirmed by examining the role of transcription factor expression, particularly Pax-6, Isl-1 and Pdx-1/Ipf-1; which were shown to be essential in pancreatic development, growth and activation of the insulin gene, leading to insulin expression (Timper et al 2006).…”

Section: Discussionsupporting

confidence: 63%

“…There is an increasing body of evidence suggesting that MSC are able to differentiate into insulin producing cells and to correct hyperglycaemia at least in rodents (Timper et al 2006;Kodama et al 2003;Tang et al 2004). Transdifferentiation is a reported phenomenon whereby one cell type committed to and progressing along a specific developmental lineage switches into another cell type of a different lineage (Song and Tuan 2004).…”

Section: Discussionmentioning

confidence: 99%

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In-vitro generation of human adipose tissue derived insulin secreting cells: up-regulation of Pax-6, Ipf-1 and Isl-1

2013

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We present a study of up-regulation of genes responsible for pancreatic development in glucose-sensitive insulin-secreting mesenchymal stem cells (IS-MSC) generated and differentiated from human adipose tissue (h-AD), with use of our specific differentiation media and without use of any xenogenic material. Anterior wall abdominal fat was collected from 56 volunteers and cultured in selfdesigned proliferation medium for 10 days. Cells were harvested by trypsinization and differentiated into insulin-expressing cells using self-designed differentiation medium for 3 days followed by evaluation for transcriptional factors Pax-6, Ipf-1, Isl-1, C-peptide and insulin secretion. Generated IS-MSC showed expression of Pax-6, Pdx-6 and Isl-1. Non-differentiated MSC as well as their further culture in absence of differentiation medium were used as negative controls. Generated 56 IS-MSC cell-lines were glucose responsive i.e. mean C-Peptide and insulin secretion levels were measured 0.41 ng/ml and 13.13 lU/ml, respectively, in absence of glucose which rose to 1.18 ng/ml and 83.42 lU/ml, respectively, following glucose challenge (p \ 0.001). The mean rise in C-peptide and insulin secretion levels was 2.88 and 6.35 fold, respectively. To conclude insulin-secreting h-AD-MSC can be generated safely and effectively with application of specific differentiation media without xenogeneic material/any genetic modification, showing expression of transcriptional factors Pax-6, Ipf-1 and Isl-1.

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Section: Discussionsupporting

confidence: 63%

Section: Discussionmentioning

confidence: 99%

In-vitro generation of human adipose tissue derived insulin secreting cells: up-regulation of Pax-6, Ipf-1 and Isl-1

2013

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“…15 However, controversial data on the ability of mesenchymal stem cells to differentiate into insulin-producing cells both in vitro and in vivo have been reported. [19][20][21][22][23] Major interest has been recently raised by the evidence that insulinproducing cells can be obtained following the in vitro expansion of an intermediate mesenchymal proliferating cell population apparently derived from a reversible epithelialmesenchymal transition of pancreatic b-cells. 24, 25 Similar results have been obtained from the exocrine compartment of human pancreas.…”

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confidence: 99%

Generation and expansion of multipotent mesenchymal progenitor cells from cultured human pancreatic islets

et al. 2007

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Cellular models and culture conditions for in vitro expansion of insulin-producing cells represent a key element to develop cell therapy for diabetes. Initial evidence that human b-cells could be expanded after undergoing a reversible epithelialmesenchymal transition has been recently negated by genetic lineage tracing studies in mice. Here, we report that culturing human pancreatic islets in the presence of serum resulted in the emergence of a population of nestin-positive cells. These proliferating cells were mainly C-peptide negative, although in the first week in culture, proliferating cells, insulin promoter factor-1 (Ipf-1) positive, were observed. Later passages of islet-derived cells were Ipf-1 negative and displayed a mesenchymal phenotype. These human pancreatic islet-derived mesenchymal (hPIDM) cells were expanded up to 10 14 cells and were able to differentiate toward adipocytes, osteocytes and chondrocytes, similarly to mesenchymal stem/precursor cells. Interestingly, however, under serum-free conditions, hPIDM cells lost the mesenchymal phenotype, formed islet-like clusters (ILCs) and were able to produce and secrete insulin. These data suggest that, although these cells are likely to result from preexisting mesenchymal cells rather than b-cells, hPIDM cells represent a valuable model for further developments toward future replacement therapy in diabetes. Cell Death and Differentiation (2007) 14, 1860-1871; doi:10.1038/sj.cdd.4402199; published online 6 July 2007Type 1 diabetes mellitus is a chronic disease resulting from the selective autoimmune destruction of pancreatic insulinproducing b-cells. Transplantation therapy represents a potential cure for type 1 diabetes mellitus, 1 but is limited by availability of human pancreatic tissue. For this reason, a great effort has been made to develop new methods for generating b-like cells in vitro, 2,3 despite of evidence that cultured b-cells have limited proliferative capacity and reduced insulin production. 4 Several attempts have been made to identify stem/progenitors cells within pancreatic tissue as a potential source for transplantable insulinproducing tissue. Unfortunately, the origin of new b-cells in adult pancreas is not known. Some in vivo studies suggested the presence of pancreatic progenitor cells within islets, 5 whereas others reported that new adult b-cells might rather originate from pre-existing b-cells. 6 Additional studies suggested that progenitor cells may reside within the pancreatic ductal epithelium 2-7 or in the acinar tissue. 8,9 Nevertheless, the exact nature and localization of adult pancreatic stem/ progenitor cells remains controversial [9][10][11][12][13][14][15][16] and their existence in vivo, at least in mice, has recently been questioned. 6 Recent evidence has shown that human embryonic stem cells are able to differentiate into insulin-producing cells in vitro, thus potentially leading to an unlimited source of cells for transplantation. 17 These two authors contributed equally to this work. 5 These two authors share...

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“…Timper et al (2006) noticed that human adipose derived stem cells (ADSCs) are able to adopt a pancreatic endocrine cell phenotype ex vivo. ADSCs were induced to differentiate into an insulin-producing cells by defined culture conditions within 3 days.…”

Section: Differentiation Of Adipose Derived Stem Cellsmentioning

confidence: 99%

“…Expression of ABCG2 was decreased and PAX-6 was no induced by the 3 days differentiation procedure. Upregulation of pancreatic transcription factors IPF-1, ISL-1, NGN3 and islet hormones was observed during the differentiation period (Timper et al 2006). Chandra (2009) demonstrated three-step differentiation protocol of IPCs from murine epididymal adipose stem cells (mE-ASCs).…”

Section: Differentiation Of Adipose Derived Stem Cellsmentioning

confidence: 99%

Differentiation of Stem Cells into Insulin-Producing Cells: Current Status and Challenges

Pokrywczyńska

Krzyzanowska

Jundziłł

et al. 2013

Arch. Immunol. Ther. Exp.

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Diabetes mellitus is one of the most serious public health challenges of the twenty-first century. Allogenic islet transplantation is an efficient therapy for type 1 diabetes. However, immune rejection, side effects of immunosuppressive treatment as well as lack of sufficient donor organs limits its potential. In recent years, several promising approaches for generation of new pancreatic b cells have been developed. This review provides an overview of current status of pancreatic and extra-pancreatic stem cells differentiation into insulin-producing cells and the possible application of these cells for diabetes treatment. The PubMed database was searched for English language articles published between 2001 and 2012, using the keyword combinations: diabetes mellitus, differentiation, insulin-producing cells, stem cells.

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Human adipose tissue-derived mesenchymal stem cells differentiate into insulin, somatostatin, and glucagon expressing cells

Cited by 397 publications

References 32 publications

In-vitro generation of human adipose tissue derived insulin secreting cells: up-regulation of Pax-6, Ipf-1 and Isl-1

In-vitro generation of human adipose tissue derived insulin secreting cells: up-regulation of Pax-6, Ipf-1 and Isl-1

Generation and expansion of multipotent mesenchymal progenitor cells from cultured human pancreatic islets

Differentiation of Stem Cells into Insulin-Producing Cells: Current Status and Challenges

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