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Expansion of transplanted islets in mice by co-transplantation with adipose tissue-derived mesenchymal stem cells.

ABSTRACT: The shortage of donor islets is a significant obstacle for widespread clinical application of pancreatic islet transplantation. To investigate whether adipose tissue-derived mesenchymal stem cells (ADSCs) induce expansion of transplanted islets, we performed co-transplantation experiments in a mouse model. Streptozotosin (STZ)-induced diabetic mice transplanted with 50 syngeneic islets remained hyperglycemic. However, hyperglycemia was ameliorated gradually when 50 islets were co-transplanted with ADSCs but not separately grafted into the contralateral kidney. Insulin and proinsulin contents of 120-day grafts containing 50 islets co-transplanted with ADSCs were significantly increased compared with those of 50 isolated islets. The Ki67-positive ratios in islets of the naïve pancreas, at 30 and 120 days grafts were 0.23%, 2.12%, and 1.52%, respectively. Ki67-positive cells were predominantly Pdx1+ and insulin+ cells. These results demonstrate that co-transplantation with ADSCs induces proliferation of transplanted islets in mice, suggesting a potential solution for the low efficiency of islet transplantation.

SUBMITTER: Tanaka T

PROVIDER: S-EPMC5986537 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Expansion of transplanted islets in mice by co-transplantation with adipose tissue-derived mesenchymal stem cells.

Tanaka Tomoko T Kojima Daibo D Mera Toshiyuki T Matsumoto Masahito M Yasunami Yohichi Y Yanase Toshihiko T

Heliyon 20180517 5

The shortage of donor islets is a significant obstacle for widespread clinical application of pancreatic islet transplantation. To investigate whether adipose tissue-derived mesenchymal stem cells (ADSCs) induce expansion of transplanted islets, we performed co-transplantation experiments in a mouse model. Streptozotosin (STZ)-induced diabetic mice transplanted with 50 syngeneic islets remained hyperglycemic. However, hyperglycemia was ameliorated gradually when 50 islets were co-transplanted wi ...[more]

PMID: 29872765

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Project description:Mesenchymal stem cells (MSCs) possess self-renewal and multipotential differentiation abilities, and they are thought to be one of the most reliable stem cell sources for a variety of cell therapies. Recently, cell therapy using MSCs has been studied as a novel therapeutic approach for cancers that show refractory progress and poor prognosis. MSCs from different tissues have different properties. However, the effect of different MSC properties on their application in anticancer therapies has not been thoroughly investigated. In this study, to characterize the anticancer therapeutic application of MSCs from different sources, we established two different kinds of human MSCs: umbilical cord blood-derived MSCs (UCB-MSCs) and adipose-tissue-derived MSCs (AT-MSCs). We used these MSCs in a coculture assay with primary glioblastoma multiforme (GBM) cells to analyze how MSCs from different sources can inhibit GBM growth. We found that UCB-MSCs inhibited GBM growth and caused apoptosis, but AT-MSCs promoted GBM growth. Terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick-end labeling assay clearly demonstrated that UCB-MSCs promoted apoptosis of GBM via tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). TRAIL was expressed more highly by UCB-MSCs than by AT-MSCs. Higher mRNA expression levels of angiogenic factors (vascular endothelial growth factor, angiopoietin 1, platelet-derived growth factor, and insulin-like growth factor) and stromal-derived factor-1 (SDF-1/CXCL12) were observed in AT-MSCs, and highly vascularized tumors were developed when AT-MSCs and GBM were cotransplanted. Importantly, CXCL12 inhibited TRAIL activation of the apoptotic pathway in GBM, suggesting that AT-MSCs may support GBM development in vivo by at least two distinct mechanisms-promoting angiogenesis and inhibiting apoptosis. The opposite effects of AT-MSCs and UCB-MSCs on GBM clearly demonstrate that differences must be considered when choosing a stem cell source for safety in clinical application.

Dataset Information

Expansion of transplanted islets in mice by co-transplantation with adipose tissue-derived mesenchymal stem cells.

Publications

Expansion of transplanted islets in mice by co-transplantation with adipose tissue-derived mesenchymal stem cells.

Similar Datasets

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