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 <i>GAS5</i> and <i>MALAT1</i> 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 <i>GAS5</i> and <i>MALAT1</i>. 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 <i>GAS5</i> and <i>MALAT1</i> 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 <i>GAS5</i> and <i>MALAT1</i>. Overall, this study reveals that molecular functions associated with healing are reduced in the absence of <i>GAS5</i> and <i>MALAT1</i>, highlighting the importance of these lncRNAs.