Abstract
Recent approaches have sought to harness the potential of stem cells to regenerate bone that is lost as a consequence of trauma or disease. Bone marrow aspirate (BMA) provides an autologous source of osteoprogenitors for such applications. However, previous studies indicated that the concentration of osteoprogenitors present in BMA is less than required for robust bone regeneration. We provide further evidence for the importance of BMA enrichment for skeletal tissue engineering strategies using a novel acoustic wave-facilitated filtration strategy to concentrate BMA for osteoprogenitors, clinically applicable for intraoperative orthopedic use. Femoral BMA from 15 patients of an elderly cohort was concentrated for the nucleated cell fraction against erythrocytes and excess plasma volume via size exclusion filtration facilitated by acoustic agitation. The effect of aspirate concentration was assessed by assays for colony formation, flow cytometry, multilineage differentiation and scaffold seeding efficiency. BMA was filtered to achieve a mean 4.2-fold reduction in volume with a corresponding enrichment of viable and functional osteoprogenitors, indicated by flow cytometry and assays for colony formation. Enhanced osteogenic and chondrogenic differentiation was observed using concentrated aspirate and enhanced cell-seeding efficiency onto allogeneic bone graft as an effect of osteoprogenitor concentration relative specifically to the concentration of erythrocytes in the aspirate. These studies provide evidence for the importance of BMA nucleated cell concentration for both cell differentiation and cell seeding efficiency and demonstrate the potential of this approach for intraoperative application to enhance bone healing.
Highlights
Tissue engineering strategies seek to harness the regenerative potential of stem or progenitor cells to replace tissue lost or damaged through injury or disease
Counts of viable cells after a 2-fold and 4-fold reduction in volume revealed a corresponding increase in the concentration of nucleated cells (NCs) in the concentrated aspirate relative to both volume and erythrocyte concentration (Figure 2A)
Flow cytometry analysis of commonly used markers for osteoprogenitors revealed enrichment of these cells in the concentrated Bone marrow aspirate (BMA) volume (Figure 2B), and an increase in the concentration of CFU-F was observed via colony-forming efficiency analysis (Figure 2C)
Summary
Tissue engineering strategies seek to harness the regenerative potential of stem or progenitor cells to replace tissue lost or damaged through injury or disease. This low cell concentration is sufficient when transplanting bulk autograft bone, where cells are translocated within their existing osteoinductive environment (and supplemented by osteoprogenitors present within the bone matrix [17,18]), robust skeletal regeneration using aspirated bone marrow appears likely to require pre-emptive cellular enrichment (19e21). These studies provide evidence for the importance of BMA nucleated cell concentration for both cell differentiation and cell seeding efficiency and demonstrate the potential of this approach for intraoperative application to enhance bone healing
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