Related Experiment Video
Updated: May 3, 2026
Isolation of Rat Adipose Tissue Mesenchymal Stem Cells for Differentiation into Insulin-producing Cells
Published on: August 29, 2022
Human adipose-derived stromal/stem cells protect against STZ-induced hyperglycemia: analysis of hASC-derived
Tatsuyoshi M Kono1, Emily K Sims, Dan R Moss
1Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Abstract:
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 β cell mass, and increased β 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 β cell death in rodent and in vitro models of type 1 diabetes through a combination of local paracrine as well as systemic effects.
Insights
Human adipose-derived stromal/stem cells (hASCs) improve glucose control and protect pancreatic beta cells. These cells secrete factors like TIMP-1, which mitigate beta cell death in type 1 diabetes models.
Area of Science:
- Stem Cell Biology
- Immunology
- Metabolic Diseases
Background:
- Adipose-derived stromal/stem cells (ASCs) show promise in treating diabetes by improving hyperglycemia.
- The specific factors from human ASCs (hASCs) responsible for these therapeutic effects are not well understood.
Purpose of the Study:
- To investigate the mechanisms by which hASCs exert their protective effects on pancreatic beta cells.
- To identify key hASC-secreted factors involved in ameliorating hyperglycemia and preserving beta cell function.
Main Methods:
- Systemic administration of hASCs in streptozotocin-treated diabetic mice.
- Coculture of islets with hASCs under normal and inflammatory conditions.
- Analysis of hASC-secreted factors, including vascular endothelial growth factor and tissue inhibitor of metalloproteinase 1 (TIMP-1).
- In vitro studies using recombinant TIMP-1 and blockade experiments.
Main Results:
- hASCs improved glucose tolerance, preserved beta cell mass, and increased beta cell proliferation in diabetic mice.
- hASCs enhanced islet viability and function in vitro, particularly under cytokine-induced stress.
- Vascular endothelial growth factor and TIMP-1 were identified as abundant hASC-secreted factors.
- TIMP-1 secretion increased with islet stress, and TIMP-1 blockade reversed hASC prosurvival effects.
- hASCs were detected in the pancreas, and serum TIMP-1 levels increased post-injection.
Conclusions:
- hASC-derived factors, particularly TIMP-1, play a crucial role in protecting beta cells from death.
- These protective effects occur through both local paracrine and systemic mechanisms.
- hASCs represent a potential therapeutic strategy for type 1 diabetes by mitigating beta cell loss.
