Abstract
BackgroundBiologics 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/PurposeThe 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 (Llo PRP) would induce migration to a greater extent than leukocyte-high platelet rich plasma (Lhi PRP) or BMC.MethodsBone marrow-derived MSCs were isolated from 8 horses. Migration of MSCs toward a biologic (BMC, Llo PRP, and Lhi 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.ResultsAll biologics resulted in a significantly greater percentage of MSCs migrated compared to the positive control (PDGF). MSCs migrated further toward BMC compared to Llo PRP. Cell migration, measured as cell flux, was greater toward BMC and Lhi PRP than Llo PRP.ConclusionThe biologics BMC and Lhi PRP elicit greater chemotaxis and chemokinesis of MSCs than Llo 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.
Highlights
Mesenchymal stromal cell (MSCs) implantation can improve tissue repair and patient function after musculoskeletal injury.[1,2,3,4,5,6,7] autologous MSC therapy is costly and time-consuming, requiring several weeks of culture to acquire sufficient cells for administration
MSCs migrated further toward bone marrow concentrate (BMC) compared to Llo platelet rich plasma (PRP)
MSCs recruited by bone marrow concentrate and platelet rich plasma preparation of the manuscript
Summary
Mesenchymal stromal cell (MSCs) implantation can improve tissue repair and patient function after musculoskeletal injury.[1,2,3,4,5,6,7] autologous MSC therapy is costly and time-consuming, requiring several weeks of culture to acquire sufficient cells for administration. This time requirement for culture delays patient treatment.[8] Use of allogeneic cells might circumvent these issues, but concerns remain about their antigenicity.[9,10,11] Further limiting the implementation of MSC therapy in patients is the lack of approval for use in humans by many governing regulatory agencies throughout the world. The hypothesis was that leukocyte-low platelet rich plasma (Llo PRP) would induce migration to a greater extent than leukocyte-high platelet rich plasma (Lhi PRP) or BMC
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