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Nanofiber-expanded human CD34(+) cells heal cutaneous wounds in streptozotocin-induced diabetic mice

Despite advances in diabetic wound care, the significant number of amputations that occur every year demands more effective therapeutics. Herein, we offer an aminated polyethersulfone nanofiber-expanded human umbilical cord blood-derived CD34(+) cells (henceforth CD34(+) cells) effective therapy, te...

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Detalles Bibliográficos
Autores principales: Kanji, Suman, Das, Manjusri, Joseph, Matthew, Aggarwal, Reeva, Sharma, Sudarshana M., Ostrowski, Michael, Pompili, Vincent J., Mao, Hai-Quan, Das, Hiranmoy
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6557810/
https://www.ncbi.nlm.nih.gov/pubmed/31182750
http://dx.doi.org/10.1038/s41598-019-44932-7
Descripción
Sumario:Despite advances in diabetic wound care, the significant number of amputations that occur every year demands more effective therapeutics. Herein, we offer an aminated polyethersulfone nanofiber-expanded human umbilical cord blood-derived CD34(+) cells (henceforth CD34(+) cells) effective therapy, tested in cutaneous wounds developed in streptozotocin-induced diabetic NOD/SCID mice. We show that systemic administration of CD34(+) cells homed to the wound site and significantly accelerated wound closure. Wound closure was associated with improved re-epithelialization and increased neovascularization; and with decreased sustained pro-inflammatory activity of NF-κB and its downstream effector molecules TNF-α, IL-1β, and IL-6 at the wound bed. This finding was further supported by the observation of a decreased number of myeloperoxidase positive neutrophils, and concomitantly increased levels of IL-10. In addition, improved granulation tissue formation was observed along with higher collagen deposition and myofibroblasts and decreased expressions of MMP-1. Mechanistically, CD34(+) cells reduced the level of MMP-1 expression by inhibiting recruitment of NF-κB to the MMP-1 promoter site in dermal fibroblasts. In summary, we provide evidence of a novel nanofiber-expanded CD34(+) stem cell therapeutic development for treating diabetic wounds by defining their cellular and molecular mechanisms.