In Vivo and In Vitro Characterization of Insulin-Producing Cells Obtained From Murine Bone Marrow

Tang, Dongqi; Cao, Li-Zhen; Burkhardt, Brant R.; Xia, Chang-Qi; Litherland, Sally A.; Atkinson, Mark A.; Yang, Lijun

doi:10.2337/diabetes.53.7.1721

Cited by 357 publications

(279 citation statements)

References 48 publications

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“…For example, in a study carried out by Chen et al, the protocol involved a two-stage protocol during which rat bone marrow mesenchymal stem cells were preinduced for 24 h and reinduced for an additional 10 h. The entire induction process took less than 48 h (Chen et al 2004). On the other hand, in another study done by Tang et al (2004) using mouse bone marrow-derived stem cells, clusters of insulin-secreting cells started to appear in 2 months with better-defined clusters appearing in 4 months. Such wide variations in the induction period are not uncommon in published literature.…”

Section: Discussionmentioning

confidence: 93%

“…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%

“…Homozygosis or mutations in these genes in mice results in a complete pancreatic agenesis (Jonsson et al 1994). 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 (Kodama et al 2003;Tang et al 2004). …”

Section: Introductionmentioning

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: Discussionmentioning

confidence: 93%

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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“…A number of studies reporting differentiation of mesenchymal stem cells (MSCs) into insulin-producing cells (Chen et al 2004;Tang et al 2004). MSCs were isolated from many organs and tissues, such as bone marrow, fat tissue, umbilical cord blood, pancreas etc.…”

Section: Differentiation Of Mesenchymal 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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“…We previously demonstrated that rat hepatic oval stem cells [28] and bone marrow-derived stem cells [29] can be induced under the high-glucose in vitro culture conditions and in vivo transplantation to trans-differentiate and mature into glucose-responsive IPCs. To determine whether long-term high-glucose culture can induce the WB-1 cells to undergo further differentiation, we continued to culture WB-1 cells in the high-glucose medium.…”

Section: Pdx1-vp16-mediated Liver-stem Cell Transdifferentiation Intomentioning

confidence: 99%

Liver stem cell-derived β-cell surrogates for treatment of type 1 diabetes

Yang

2006

Autoimmunity Reviews

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Consistent with the common embryonic origin of liver and pancreas as well the similar glucosesensing systems in hepatocytes and pancreatic β-cells, it should not be surprising that liver stem cells/hepatocytes can transdifferentiate into insulin-producing cells under high-glucose culture conditions or by genetic reprogramming. Persistent expression of the pancreatic duodenal homeobox-1 (Pdx1) transcription factor or its super-active form Pdx1-VP16 fusion protein in hepatic cells reprograms these cells into pancreatic β-cell precursors. In vitro culture at elevated glucose concentrations or in vivo exposure to a hyperglycemia are required for further differentiation and maturation of liver-derived pancreatic β-cell precursor into functional insulinproducing pancreatic β-like cells. Under appropriate conditions, multiple pancreatic transcription factors can work in concert to reprogram liver stem/adult liver cells into functional insulinproducing cells. If such autologous liver-derived insulin-producing cells can be made to escape the type 1 diabetes-associated autoimmunity, they may serve as a valuable cell source for future cell replacement therapy without the need for life-long immunosuppression.

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In Vivo and In Vitro Characterization of Insulin-Producing Cells Obtained From Murine Bone Marrow

Cited by 357 publications

References 48 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

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

Liver stem cell-derived β-cell surrogates for treatment of type 1 diabetes

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