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Angiogenin derived from ABCB5+ mesenchymal stem cells improves diabetic wound via enhancing angiogenesis

ABSTRACT: Severe angiopathy has been postulated as a major driver for diabetes associated secondary complications. So far the knowledge on underlying mechanisms and thereon based therapeutic options to attenuate these pathologies are limited. Here we systematically administered ABCB5+ MSCs for the treatment of chronic non-healing diabetic wounds employing db/db mice, a type II diabetes model as their number markedly declined during diabetes. We found that administration of ABCB5+ MSCs markedly accelerates wound closure in diabetic db/db mice as opposed to the vehicle treated control group. Strikingly, administration of ABCB5+ MSCs at the edges of the diabetic wounds triggered considerable neoangiogenesis, most likely by the releasing a Ribonuclease angiogenin that was identified through secretome analysis of ABCB5+ MSCs. Interestingly, silencing of angiogenin in ABCB5+ MSCs significantly delayed wound closure in diabetic db/db mice indicating its key role in skin regeneration. Moreover, angiogenin also impacted the polarization of macrophages. The findings from this study will provide novel insight into the unique capacity of ABCB5+ MSCs to mount an adaptive response at the wound site with the delivery of angiogenic molecules holds significant promise for the therapy of non-healing diabetes foot ulcers, and other pathologies with impaired angiogenesis. The benefits for refined stem cell based therapies is virtually unlimited.

ORGANISM(S): Homo sapiens

PROVIDER: GSE144169 | GEO | 2020/01/24

REPOSITORIES: GEO

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Angiogenin Released from ABCB5+ Stromal Precursors Improves Healing of Diabetic Wounds by Promoting Angiogenesis

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Smad7-based biologic targeting epidermis and stroma promotes healing of diabetic wounds in mice and pigs

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Gene expression profile at single cell level of skin cells isolated from db/db mice

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