Hair follicle mesenchymal stem cell exosomal lncRNA H19 inhibited NLRP3 pyroptosis to promote diabetic mouse skin wound healing

Abstract

Skin wounds caused by diabetes are a major medical problem. Mesenchymal stem cell-derived exosomes hold promise to quicken wound healing due to their ability to transfer certain molecules to target cells, including mRNAs, microRNAs, lncRNAs, and proteins. Nonetheless, the specific mechanisms underlying this impact are not elucidated. Therefore, this research aimed to investigate the effect of MSC-derived exosomes comprising long non-coding RNA (lncRNA) H19 on diabetic skin wound healing. Hair follicle mesenchymal stem cells (HF-MSCs) were effectively isolated and detected, and exosomes (Exo) were also isolated smoothly. Pretreatment with 30 mM glucose for 24 h (HG) could efficiently induce pyroptosis in HaCaT cells. Exosomal H19 enhanced HaCaT proliferation and migration and inhibited pyroptosis by reversing the stimulation of the NLRP3 inflammasome. Injection of exosomes overexpressing lncRNA H19 to diabetic skin wound promoted sustained skin wound healing, whereas sh-H19 exosomes did not have this effect. In conclusion, Exosomes overexpressing H19 promoted HaCaT proliferation, migration and suppressed pyroptosis both in vitro and in vivo . Therefore, HFMSC-derived exosomes that overexpress H19 may be included in strategies for healing diabetic skin wounds.

Stem Cell-Derived Extracellular Vesicles: Promising Therapeutic Opportunities for Diabetic Wound Healing

“…Yang et al found that lncRNA H19 overexpression from HF-MSC-exos promoted HaCaT proliferation, migration, and inhibited apoptosis in vitro, and further enhanced diabetic skin wound healing in mouse models in vivo by reversing the stimulation of NLRP3 inflammasome-induced pyroptosis. 114 …”

Exosomes: The emerging mechanisms and potential clinical applications in dermatology

“…HucMSC-exos improved angiogenesis in the diabetic wound by transferring lncRNAs related to angiogenesis, such as PANTR1, H19, OIP5-AS1, and NR2F1-AS1 97 . Hair follicle MSC exosomal lncRNA H19 promoted proliferation and migration and inhibited NLRP3-related pyroptosis in keratinocytes to promote diabetic wound healing 98 . In addition, genetic engineering editing in MSCs can improve the therapeutic effect of MSC-exos on diabetic wounds.…”

Obesity and Wound Healing: Focus on Mesenchymal Stem Cells

“…In fact, ADSC-derived exosomes have been shown to inhibit both adipogenic differentiation and lipogenesis in ADSCs through activation of the Hedgehog (Hh) pathway [ 165 , 166 ]. Despite the promising results achieved with MSCs in the treatment of diabetes and its associated comorbidities, clinical data on the efficacy of autologous ADSCs are still lacking [ 167 , 168 ].…”