PhD Student Manipal Centre for Biotherapeutics Research, Manipal Academy of Higher Education, Manipal, Karnataka, India MAHE, Manipal, Karnataka, India
Abstract: Wound healing is a multifaceted biological process that necessitates synchronized cellular activities, involving cell proliferation, migration, and the remodeling of the extracellular matrix. Mesenchymal stromal cells (MSCs) have received significant attention due to their regenerative capabilities, primarily attributed to their secretome, which consists of bioactive molecules and extracellular vesicles. Recent studies indicate that priming MSCs with external factors can enhance their therapeutic efficacy. This study investigates the effects of Netrin-1 (N1) priming on the regenerative potential of MSC-derived secretome, focusing on key cellular functions essential for wound healing. MSCs were isolated from Wharton's Jelly of human umbilical cords, characterized, and subjected to priming with recombinant N1 protein for 48 hours. Further the conditioned media from these cultures were collected and assessed for their wound healing potential. Functional assays demonstrated that the secretome from N1-primed MSCs exhibited significantly improved wound healing capabilities compared to that of unprimed MSCs. Specifically, the primed secretome displayed enhanced anti-inflammatory properties by facilitating macrophage polarization, promoting fibroblast migration and proliferation, and significantly increasing tube formation by HUVECs, indicating superior vascularization and regenerative abilities. These findings indicate that priming of MSCs with N1 results in a notable increase in the secretion of factors associated with cell survival, anti-inflammation, and angiogenesis in the conditioned media. Thus, the N1-primed MSC secretome emerges as a potent therapeutic agent for wound healing, vascularization, and regeneration. Future research will focus on developing and evaluating an appropriate delivery system for the secretome to further enhance its therapeutic potential and ensure targeted delivery in preclinical models for wound healing. This integrated approach opens significant avenues for advancing therapeutic modalities in regenerative medicine.
Funding Source: Manipal Academy of Higher Education
