Human Adipose Tissue-Derived Mesenchymal Stem Cells Combined With Hematopoietic Stem Cell Transplantation Synthesize Insulin

Trivedi, Hargovind L; Vanikar, Aruna V; Thakker, U.; Firoze, A.; Dave, Shruti D; Patel, Chirag H.; Patel, J. D.; Bhargava, Anuj; Shankar, V.

doi:10.1016/j.transproceed.2008.03.113

Cited by 100 publications

(79 citation statements)

References 7 publications

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“…A cohort of diabetic patients in whom insulin secreting MSC were transplanted had no side/adverse effects or malignancy noted so far over a follow-up of 2.5 years (Trivedi et al 2008).…”

Section: Discussionmentioning

confidence: 94%

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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“…A cohort of diabetic patients in whom insulin secreting MSC were transplanted had no side/adverse effects or malignancy noted so far over a follow-up of 2.5 years (Trivedi et al 2008).…”

Section: Discussionmentioning

confidence: 94%

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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“…Reprogramming memory may suggest incomplete reprogramming of iPSCs, while if pPiPSCs could retain the properties of original cells that could be beneficial in clinical practice or basic research, they may have useful applications. ADSCs possess the capacity of multipotency (Oswald et al 2004, Lindroos et al 2011, high activity of secretion (Spaggiari et al 2009, Nguyen et al 2010, homing (Lamfers et al 2009), and immune modification (Yanez et al 2006), and have been widely used in cell replacement therapy (CRT) and clinical research (Trivedi et al 2008, Ichim et al 2010. We questioned as to whether pPiPSCs retained these favorable characteristics after reprogramming.…”

Section: Discussionmentioning

confidence: 99%

“…Owing to their low immunogenicity and immunosuppression in vivo and in vitro, ADSCs can be applied in healing immunodeficiency diseases such as graft-vs-host diseases (Yanez et al 2006), diabetes (Trivedi et al 2008), and rheumatoid arthritis (Ichim et al 2010). When antigens enter the body, their major histocompatibility complex (MHC) is the first to be recognized and provides the first signal of the immune response.…”

Section: Discussionmentioning

confidence: 99%

Characterization of porcine partially reprogrammed iPSCs from adipose-derived stem cells

Wei¹,

Li²,

Zhang³

et al. 2015

Reproduction

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Partially reprogrammed induced pluripotent stem cells (PiPSCs) have great potential for investigating reprogramming mechanisms and represent an alternative potential material for making genetically modified animals and regenerative medicine. To date, PiPSCs have scarcely been reported in detail when compared with mice and humans. In this study, we obtained PiPSCs from porcine adipose-derived stem cells (pADSCs) by ectopic expression of human transcription factors (OCT4, SOX2, c-MYC, and KLF4) in feeder-free condition. The morphology and proliferation activity of porcine PiPSCs (pPiPSCs) were similar to those of porcine fully reprogrammed iPSCs (pFiPSCs); furthermore, pPiPSCs expressed higher levels of the typical surface molecules (CD29) found in pADSCs. However, pPiPSCs were negative for key proteins (NANOG) connected with stemness and possessed lower differentiation ability in vivo and in vitro. When differentiationinhibiting factors were withdrawn, pPiPSCs-derived cells (pPiPSC-DCs) showed similar features to pADSCs in many aspects, including proliferation, differentiation, and immunosuppression. When both types of cells were used to produce cloned embryos, we found that the blastocyst formation rate of 19DC (one of the pPiPSC-DC cell lines)-derived cloned embryos was obviously higher than that of others. The total cell number of 19DC-derived blastocysts was significantly higher than the 30DC (one pFiPSC-DC cell line)-derived blastocysts. In all, through limited differentiation ability, the proliferation activity of pPiPSCs is similar to that of pFiPSCs, and pPiPSCs can retain several of the features of pADSCs, which are beneficial to cell therapy. Furthermore, the differentiation of pPiPSCs is more favorable for producing high-quality reconstructed embryos. Free Chinese abstract: A Chinese translation of this abstract is freely available at

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“…In vitro functionality of these cells was also confirmed by insulin production and release in a glucose-responsive manner. [4][5][6] We decided to infuse the cells in portal circulation since liver is the most tolerogenic organ 7 . LADA is believed to be an auto-immune disorder and once the cells are infused in to thymus, it helps in preventing the rejection of these cells by inducing central tolerance 8 .…”

Section: Discussionmentioning

confidence: 99%

Autologous Adipose Tissue Derived Insulin-Secreting Mesenchymal Stem Cell Transplantation In Late Onset of Autoimmune Mediated Diabetes Mellitus (LADA) – Case Report

Dave

Vanikar

Trivedi³

et al. 2013

Int Jour of Biomed Res

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Human Adipose Tissue-Derived Mesenchymal Stem Cells Combined With Hematopoietic Stem Cell Transplantation Synthesize Insulin

Cited by 100 publications

References 7 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

Characterization of porcine partially reprogrammed iPSCs from adipose-derived stem cells

Autologous Adipose Tissue Derived Insulin-Secreting Mesenchymal Stem Cell Transplantation In Late Onset of Autoimmune Mediated Diabetes Mellitus (LADA) – Case Report

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