Application of adipose-derived mesenchymal stem cell 3D structure, Microblock, as a skin regeneration therapy

Adipose-derived mesenchymal stem cells (Ad-MSCs) have been widely studied for their regenerative potential in skin wound healing due to their ability to modulate inflammation, regulate immune responses, promote angiogenesis, and facilitate extracellular matrix (ECM) remodeling. However, the therapeutic efficacy of single-cell transplantation is often limited by low engraftment efficiency and transient effects, restricting its long-term regenerative impact. To overcome these challenges, we developed a spheroid-like structure, Microblock (MiB), designed to enhance the expression of key regenerative proteins compared to conventional single-cell Ad-MSCs. To evaluate its therapeutic potential, we conducted a wound healing assay in a rat model and performed proteomic analysis to investigate its underlying molecular mechanisms. Additionally, a comprehensive non-clinical safety evaluation, including toxicity, tumorigenicity, biodistribution, and persistence studies, was conducted to assess its feasibility for clinical application. Our findings demonstrated that MiB significantly enhanced skin regeneration and tissue remodeling, as evidenced by the upregulation of ECM-related proteins such as Collagen Type I and fibronectin and the activation of TGF-β1 signaling. Furthermore, key TGF-β target proteins associated with VEGFA signaling were identified, and MiB treatment resulted in a substantial increase in collagen deposition. These results suggest that MiB effectively promotes skin regeneration by reinforcing ECM remodeling and activating essential signaling pathways. Compared to single-cell Ad-MSC transplantation, MiB exhibited superior regenerative potential, highlighting its promise as a novel cell-based therapeutic for skin repair and laying the groundwork for future clinical applications.