Abstract:

Diabetic ulcers afflict millions of people worldwide, and new therapeutic modalities are required to tackle this difficult clinical problem. Extracellular vesicles (EVs) are plasma membrane-derived vesicles, and they can be released into the microenvironment from stem cells to stimulate tissue regeneration. Since adipose-derived stem cells (ASCs) are abundant and easily accessible, ASC-EVs harvested from healthy donors can become a “ready-to-use” therapeutic tool without the immunorejection side effects of allogeneic cell therapy. Previously our team has demonstrated the enhanced regenerative capabilities of 3D-cultured ASCs, including cell spheroids and cell sheets. Therefore, we aimed to investigate the therapeutic potential of EVs derived from 3D-cultured ASCs on diabetic wound healing.
Our data show that ASCs produce more EVs in the 3D culture condition, and these EVs also promoted endothelial cell proliferation and in vitro angiogenesis more effectively relative to EVs derived from monolayer ASCs. Moreover, in a cutaneous wound model of diabetic rats, ASC-EVs derived from 3D-culture condition showed a superior capability to enhance wound healing. Hence, the study provides important information regarding future application of EVs from 3D-cultured ASCs for patients with diabetic ulcers. The strategy of using EVs derived from 3D culture technique of ASCs holds great potential for future application in angiogenesis and wound healing therapies.

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