p16INK4A-Expressing Mesenchymal Stromal Cells Restore the Senescence-Clearance-Regeneration Sequence that is Impaired in Chronic Muscle Inflammation

Chikenji, Takako; Saito, Yuki; Konari, Naoto; Nakano, Masako; Mizue, Yuka; Otani, Miho; Fujimiya, Mineko

doi:10.2139/ssrn.3311841

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“…Accumulation of p15 INK4B + senescent PDGFR-α+ cells is also observed in diabetic patients, and non-diabetic patients have a decreased number of senescent cells during wound healing. PDGFR-α+ mesenchymal stromal cells in skeletal muscle exhibit transient senescence, and this promotes muscle regeneration after acute muscle injury 52,53 . PDGFR-α+ or vimentin+ cells in neonatal hearts exhibit transient senescence to promote regeneration 6,7 .…”

Section: Discussionmentioning

confidence: 99%

Altered regulation of mesenchymal cell senescence promotes pathological changes associated with diabetic wound healing

Kita

Saito

Miura

et al. 2021

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Pathologic diabetic wound healing is caused by sequential and progressive deterioration of hemostasis, inflammation, proliferation, and resolution/remodeling. Cellular senescence promotes physiological wound process; however, diabetic wounds exhibit low levels of senescent factors and accumulate senescent cells, which impair the healing process. In this study, we demonstrate that the number of p15INK4B + senescent PDGFR-α + mesenchymal cells in adipose tissue transiently increases in early phases of wound healing in non-diabetic mice and humans. Transplantation of adipose tissue from diabetic mice into non-diabetic mice results in wound healing impairment and an alteration in the cellular senescence-associated secretory phenotype (SASP), suggesting that insufficient induction of adipose tissue senescence after injury is a pathological mechanism of diabetic wound healing. These results give novel insight into how regulation of senescence in adipose tissue contributes to the wound healing process and provide the basis for the development of therapeutic approaches for wound healing impairment in diabetes.

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Section: Discussionmentioning

confidence: 99%