Abstract
Bone marrow mesenchymal stem/stromal cells (BMSCs) show great promise for bone repair, however they are isolated by an invasive bone marrow harvest and their regenerative potential decreases with age. Conversely, cord blood can be collected non-invasively after birth and contains MSCs (CBMSCs) that can be stored for future use. However, whether CBMSCs can replace BMSCs targeting bone repair is unknown. This study evaluates the in vitro osteogenic potential of unprimed, osteogenically primed, or chondrogenically primed CBMSCs and BMSCs and their in vivo bone forming capacity following ectopic implantation on biphasic calcium phosphate ceramics in nude mice. In vitro, alkaline phosphatase (intracellular, extracellular, and gene expression), and secretion of osteogenic cytokines (osteoprotegerin and osteocalcin) was significantly higher in BMSCs compared with CBMSCs, while CBMSCs demonstrated superior chondrogenic differentiation and secretion of interleukins IL-6 and IL-8. BMSCs yielded significantly more cell engraftment and ectopic bone formation compared to CBMSCs. However, priming of CBMSCs with either chondrogenic or BMP-4 supplements led to bone formation by CBMSCs. This study is the first direct quantification of the bone forming abilities of BMSCs and CBMSCs in vivo and, while revealing the innate superiority of BMSCs for bone repair, it provides avenues to induce osteogenesis by CBMSCs.
Highlights
Bone marrow mesenchymal stem/stromal cells (BMSCs) show great promise for bone repair, they are isolated by an invasive bone marrow harvest and their regenerative potential decreases with age
Both BMSCs and collected non-invasively after birth and contains mesenchymal stromal cell (MSC) (CBMSCs) showed positive expression of typical stem cell surface markers CD105, CD90, CD73, while they were negative for CD45, CD34, and CD3
Extracellular alkaline phosphatase (ALP) expression was significantly higher for BMSCs compared with CBMSCs at both days 7 and 14 (Fig. 1D,F)
Summary
Bone marrow mesenchymal stem/stromal cells (BMSCs) show great promise for bone repair, they are isolated by an invasive bone marrow harvest and their regenerative potential decreases with age. BMSCs yielded significantly more cell engraftment and ectopic bone formation compared to CBMSCs. priming of CBMSCs with either chondrogenic or BMP-4 supplements led to bone formation by CBMSCs. This study is the first direct quantification of the bone forming abilities of BMSCs and CBMSCs in vivo and, while revealing the innate superiority of BMSCs for bone repair, it provides avenues to induce osteogenesis by CBMSCs. Autologous bone grafting remains the gold standard method employed clinically to heal large bone defects, with bone being the second most transplanted tissue, after blood. CBMSCs that have undergone osteogenic priming prior to transplantation have demonstrated enhanced mineralization and bone regeneration in ectopic sites[16] and critical-sized bone defects[17] respectively Taken together, these evidences suggest that CBMSCs may be a possible alternative to BMSCs for bone regeneration since they exhibit osteogenic properties, avoid the invasive BM harvesting procedure, and can be banked at birth for later use. To establish whether priming of CBMSCs is a prerequisite prior to implantation, BMSCs and CBMSCs were transplanted after priming with standard osteogenic supplements, bone morphogenetic protein-4 (BMP-4), or chondrogenic differentiation
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