期刊
STEM CELLS
卷 32, 期 7, 页码 1831-1842出版社
WILEY
DOI: 10.1002/stem.1676
关键词
Diabetes; Adipose stem cells; Pancreas; Caspase; Cellular proliferation; Tissue regeneration
资金
- NIH [T32 HL079995, T32 DK065549, K08 DK080225, R03 DK089147, R01 DK093954, R01 CA138237-01, R01 CA155294-01]
- VA Merit Award [1I01BX001733]
- Sigma Beta Sorority
- Cryptic Masons Medical Research Foundation
- VA Merit Review [BX000860]
- NIDDK
Adipose-derived stromal/stem cells (ASCs) ameliorate hyperglycemia in rodent models of islet transplantation and autoimmune diabetes, yet the precise human ASC (hASC)-derived factors responsible for these effects remain largely unexplored. Here, we show that systemic administration of hASCs improved glucose tolerance, preserved beta cell mass, and increased beta cell proliferation in streptozotocin-treated nonobese diabetic/severe combined immunodeficient mice. Coculture experiments combining mouse or human islets with hASCs demonstrated that islet viability and function were improved by hASCs following prolonged culture or treatment with proinflammatory cytokines. Analysis of hASC-derived factors revealed vascular endothelial growth factor and tissue inhibitor of metalloproteinase 1 (TIMP-1) to be highly abundant factors secreted by hASCs. Notably, TIMP-1 secretion increased in the presence of islet stress from cytokine treatment, while TIMP-1 blockade was able to abrogate in vitro prosurvival effects of hASCs. Following systemic administration by tail vein injection, hASCs were detected in the pancreas and human TIMP-1 was increased in the serum of injected mice, while recombinant TIMP-1 increased viability in INS-1 cells treated with interleukin-1beta, interferon-gamma, and tumor necrosis factor alpha. In aggregate, our data support a model whereby factors secreted by hASCs, such as TIMP-1, are able to mitigate against beta cell death in rodent and in vitro models of type 1 diabetes through a combination of local paracrine as well as systemic effects.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据