Abstract
BackgroundBone marrow-derived mononuclear cells (BM-MNC) consist of a heterogeneous mix of mesenchymal stem cells (MSC), hematopoietic progenitor cells (HPC), endothelial progenitor cells (EPC), monocytes, lymphocytes and pluripotent stem cells. Whereas the importance of MSC and EPC has been well documented in bone healing and regeneration studies, the role of pluripotent stem cells is still poorly understood. In the present study we evaluated if and how Very Small Embryonic Like cells (VSEL), isolated from rat BM-MNC, contribute to bone healing.MethodsLarge bone defects were made in the femurs of 38 Sprague Dawley female rats and treated with β-TCP scaffold granules seeded with male VSEL; BM-MNC, VSEL-depleted BM-MNC or scaffold alone, and bone healing was evaluated at 8 weeks post-surgery.ResultsBone healing was significantly increased in defects treated with VSEL and BM-MNC, compared to defects treated with VSEL-depleted BM-MNC. Donor cells were detected in new bone tissue, in all the defects treated with cells, and in fibrous tissue only in defects treated with VSEL-depleted BM-MNC. The number of CD68+ cells was the highest in the VSEL-depleted group, whereas the number of TRAP positive cells was the lowest in this group.ConclusionsBased on the results, we can conclude that VSEL play a role in BM-MNC induced bone formation. In our rat femur defect model, in defects treated with VSEL-depleted BM-MNC, osteoclastogenesis and bone formation were decreased, and foreign body reaction was increased.
Highlights
Bone non-unions and large defects, due to trauma, disease, excision of tumors or congenital defects, are important clinical problems that represent a major challenge for the patients who suffer with them, the physicians who treat them and the healthcare system, responsible for their high costs
Bone marrow-derived mononuclear cells (BM-MNC) consists of a heterogeneous mix of mononuclear cells containing mesenchymal stem cells (MSC), hematopoietic progenitor cells (HPC), endothelial progenitor cells (EPC), and pluripotent stem cells [5]
Adult pluripotent stem cells have been described by several groups, and depending on the group and the isolation protocol used, have been assigned different names, including, spore-like stem cells [6], multipotent adult stem cells (MASC) [7], multilineage-differentiating stress enduring (Muse) cells [8], multipotent adult progenitor cells (MAPC) [9], and very small embryonic-like stem cells (VSEL) [10, 11]
Summary
Bone non-unions and large defects, due to trauma, disease, excision of tumors or congenital defects, are important clinical problems that represent a major challenge for the patients who suffer with them, the physicians who treat them and the healthcare system, responsible for their high costs. Current treatments such as callus distraction, cortical allografts, and metallic, polymeric or ceramic implants, enjoy varying degrees of success, autologous bone grafts are still considered to be the gold standard treatment. Bone marrow-derived mononuclear cells (BM-MNC) consist of a heterogeneous mix of mesenchymal stem cells (MSC), hematopoietic progenitor cells (HPC), endothelial progenitor cells (EPC), monocytes, lymphocytes and pluripotent stem cells. In the present study we evaluated if and how Very Small Embryonic Like cells (VSEL), isolated from rat BM-MNC, contribute to bone healing
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