Facilitated recruitment of mesenchymal stromal cells by bone marrow concentrate and platelet rich plasma

BACKGROUND: Biologics containing growth factors are frequently used to enhance healing after musculoskeletal injuries. One mechanism of action is thought to be though the ability of biologics to induce homing and migration of endogenous mesenchymal stromal cells (MSCs) to a target tissue. However, the ability of biologics to stimulate chemotaxis (directed migration of cells) and chemokinesis (increase rate of cell migration) of MSCs is unknown. HYPOTHESIS/PURPOSE: The aim of this study was to directly compare the ability of biologics including platelet rich plasma (PRP) and bone marrow concentrate (BMC) to induce MSC migration. The hypothesis was that leukocyte-low platelet rich plasma (L(lo) PRP) would induce migration to a greater extent than leukocyte-high platelet rich plasma (L(hi) PRP) or BMC. METHODS: Bone marrow-derived MSCs were isolated from 8 horses. Migration of MSCs toward a biologic (BMC, L(lo) PRP, and L(hi) PRP) or the positive control platelet derived growth factor (PDGF) was continuously traced and measured for 24hrs using time-lapse microscopy and a microfluidics device. Cell migration, chemotaxis and chemokinesis were determined by measurements of displacement, number of cells migrated, and cell flux. RESULTS: All biologics resulted in a significantly greater percentage of MSCs migrated compared to the positive control (PDGF). MSCs migrated further toward BMC compared to L(lo) PRP. Cell migration, measured as cell flux, was greater toward BMC and L(hi) PRP than L(lo) PRP. CONCLUSION: The biologics BMC and L(hi) PRP elicit greater chemotaxis and chemokinesis of MSCs than L(lo) PRP. However, all biologics recruited the same number of MSCs suggesting that differences in other regenerative effects, such as growth factor concentration, between biologics should be strongly considered when choosing a biologic for treatment of musculoskeletal injuries. The results of this study have the potential to reduce the need, risks, and costs associated with MSC culture and delivery.