lncRNAs GAS5 and MALAT1 Contained in Human Adipose Stem Cell (hASC)-Derived Exosomes Drive the Cell-Free Repair and Regeneration of Wounds In Vivo.

Wound healing progresses through four phases: hemostasis, inflammation, proliferation, and remodeling. Wounds may become chronic if this process is disrupted. The use of small extracellular vesicle (sEV; EVs < 200 nm) exosomes (exo; ~40-120 nm) derived from human adipose stem cells (hASCs) as a treatment for wounds is well studied. The cargo of these exosomes is of great interest as this accelerates wound healing. Our previous studies identified lncRNAs GAS5 and MALAT1 as packaged and enriched in hASC exosomes. In this study, we use a rat model to examine the effects on wound healing when hASC exosomes are depleted of GAS5 and MALAT1. Rats were wounded and wounds were treated with 100 μg hASC(exo) or hASC(exo)-G-M every 2 days for 1 week. qPCR was completed to evaluate the molecular effects of depletion of GAS5 and MALAT1 from hASC(exo). RNAseq was performed on wound tissue to evaluate the molecular mechanisms changed by hASC(exo)-G-M in wound healing. While hASC(exo)-G-M significantly improved wound healing rate compared to control wounds, healing occurred slower than in wounds treated with hASC(exo) that were not depleted of GAS5 and MALAT1. Overall, this study reveals that molecular functions associated with healing are reduced in the absence of GAS5 and MALAT1, highlighting the importance of these lncRNAs.