ISOLATION OF BONE MARROW MESENCHYMAL STEM CELLS EMBEDDED IN NATIVE TISSUE STROMA YIELDS ENRICHED HARVEST, IMPROVED ADHERENCE AND PROLIFERATION, AND UNIQUE SECRETOME

Background: The field of orthobiologics traditionally utilizes cellular products, including bone-marrow aspirate concentrate (BMAC), micronized adipose tissue, and platelet preparations to address pain from degenerative processes, orthopedic injuries and medical conditions characterized by chronic inflammation and tissue degradation. For BMAC, maximizing the concentration of mesenchymal stem cells (MSCs) in a reduced volume is thought to allow for the therapeutic delivery of the cellular concentrate, secretome, and extracellular vesicles to a site of orthopedic injury or surgical repair. The extracellular matrix (ECM) within the bone marrow stroma contains collagens and proteoglycans known to regulate cell proliferation, migration, differentiation, and cell-cell communication among resident bone marrow cells. This study aimed to evaluate the cellular effects on MSC health and function when harvested to retain their native tissue stroma. Methods: We evaluated a novel and unique processing method and device (BMAX™) to mechanically generate a purified MSC product derived from bone marrow in a nonenzymatic manner. BMAX™ products, including cells and stroma, were plated in MSC culture media and incubated for 3–14 days (P0-P1) before evaluation with flow cytometry for cell phenotyping and immunoassays for secretome profiling. Results: The orthobiologic product containing three-dimensional stromal components can be produced in minutes using an automated bedside device requiring minimal benchtop space. We found increased MSC adherence, improved proliferative density in culture, and significantly elevated enrichment of stromal-derived MSCs versus traditional BMAC centrifugation-based preparations. Further, we demonstrate a unique secretome profile in BMAX™ versus traditional BMAC centrifugation-based preparations. Conclusions: These qualities provide a novel and unique platform for autologous and allogeneic bone-marrow-derived therapy to better address inflammatory and destructive processes that may improve bone-marrow-derived cell therapies’ efficacy.