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Stem Cell Reports. 2017 Sep 12;9(3):807-819. doi: 10.1016/j.stemcr.2017.07.012. Epub 2017 Aug 10.

Mitigating Ischemic Injury of Stem Cell-Derived Insulin-Producing Cells after Transplant.

Author information

1
Department of Surgery, University of California San Francisco, San Francisco, CA 94143, USA.
2
UCSF Diabetes Center, University of California San Francisco, San Francisco, CA 94143, USA; Barbara Davis Center for Diabetes, School of Medicine, University of Colorado Denver, Aurora, CO 80045, USA.
3
UCSF Diabetes Center, University of California San Francisco, San Francisco, CA 94143, USA.
4
Department of Surgery, University of California San Francisco, San Francisco, CA 94143, USA; UCSF Diabetes Center, University of California San Francisco, San Francisco, CA 94143, USA. Electronic address: qizhi.tang@ucsf.edu.

Abstract

The advent of large-scale in vitro differentiation of human stem cell-derived insulin-producing cells (SCIPC) has brought us closer to treating diabetes using stem cell technology. However, decades of experiences from islet transplantation show that ischemia-induced islet cell death after transplant severely limits the efficacy of the therapy. It is unclear to what extent human SCIPC are susceptible to ischemia. In this study, we show that more than half of SCIPC die shortly after transplantation. Nutrient deprivation and hypoxia acted synergistically to kill SCIPC in vitro. Amino acid supplementation rescued SCIPC from nutrient deprivation, likely by providing cellular energy. Generating SCIPC under physiological oxygen tension of 5% conferred hypoxia resistance without affecting their differentiation or function. A two-pronged strategy of physiological oxygen acclimatization during differentiation and amino acid supplementation during transplantation significantly improved SCIPC survival after transplant.

KEYWORDS:

graft survival; hypoxia; ischemia; islet transplant; nutrient deprivation; stem cell-derived insulin-producing cells; type 1 diabetes

PMID:
28803916
PMCID:
PMC5599226
DOI:
10.1016/j.stemcr.2017.07.012
[Indexed for MEDLINE]
Free PMC Article

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