Association between in vivo bone formation and ex vivo migratory capacity of human bone marrow stromal cells

Abstract

IntroductionThere is a clinical need for developing systemic transplantation protocols for use of human skeletal stem cells (also known bone marrow stromal stem cells) (hBMSC) in tissue regeneration. In systemic transplantation studies, only a limited number of hBMSC home to injured tissues suggesting that only a subpopulation of hBMSC possesses “homing” capacity. Thus, we tested the hypothesis that a subpopulation of hBMSC defined by ability to form heterotopic bone in vivo, is capable of homing to injured bone.MethodsWe tested ex vivo and in vivo homing capacity of a number of clonal cell populations derived from telomerized hBMSC (hBMSC-TERT) with variable ability to form heterotopic bone when implanted subcutaneously in immune deficient mice. In vitro transwell migration assay was used and the in vivo homing ability of transplanted hBMSC to bone fractures in mice was visualized by bioluminescence imaging (BLI). In order to identify the molecular phenotype associated with enhanced migration, we carried out comparative DNA microarray analysis of gene expression of hBMSC-derived high bone forming (HBF) clones versus low bone forming (LBF) clones.ResultsHBF clones were exhibited higher ex vivo transwell migration and following intravenous injection, better in vivo homing ability to bone fracture when compared to LBF clones. Comparative microarray analysis of HBF versus LBF clones identified enrichment of gene categories of chemo-attraction, adhesion and migration associated genes. Among these, platelet-derived growth factor receptor (PDGFR) α and β were highly expressed in HBF clones. Follow up studies showed that the chemoattractant effects of PDGF in vitro was more enhanced in HBF compared to LBF clones and this effect was reduced in presence of a PDGFRβ-specific inhibitor: SU-16 f. Also, PDGF exerted greater chemoattractant effect on PDGFRβ+ cells sorted from LBF clones compared to PDGFRβ- cells.ConclusionOur data demonstrate phenotypic and molecular association between in vivo bone forming ability and migratory capacity of hBMSC. PDGFRβ can be used as a potential marker for the prospective selection of hBMSC populations with high migration and bone formation capacities suitable for clinical trials for enhancing bone regeneration.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-015-0188-9) contains supplementary material, which is available to authorized users.

Optimization of pure platelet-rich plasma preparation: A comparative study of pure platelet-rich plasma obtained using different centrifugal conditions in a single-donor model

“…IL-1β and TNF-α are the primary cytokines for inflammation and matrix degradation ( 8 , 13 , 20 , 25 ). Therefore, the present study also assessed the concentration of IL-1β and TNF-α in PCP and P-PRP obtained using different conditions.…”

“…The results demonstrated that P-PRP obtained using the optimal conditions significantly promoted the proliferation and migration of hBMSCs and hACs compared with P-PRP obtained using other conditions. Numerous studies have demonstrated that the promotion of proliferation and migration of hBMSCs is beneficial for the regeneration of bone ( 25 ) and cartilage ( 32 ) and that the promotion of proliferation and migration of hACs is beneficial for the treatment of arthritis ( 33 ). Therefore, P-PRP obtained using the optimal conditions identified may also be more effective in the treatment of bone defects, osteochondral defects and arthritis.…”

Activation, homing, and role of the mesenchymal stem cells in the inflammatory environment

“…However, the findings of the present study suggest that only a limited number of BMSCs used in systemic transplantations possess homing capacity toward injured tissue. A molecular signature that defines this population has been identified, and a surface marker PDGFRβ can be employed for potential isolation of the BMSCs with enhanced migratory capacity 87. Recent data also demonstrate functional association between in vivo bone forming ability and homing capacity of BMSCs.…”

Preparing Platelet-Rich Plasma with Whole Blood Harvested Intraoperatively During Spinal Fusion

“…Our results demonstrated that PRP prepared from harvested blood and venous blood had similar effects on promoting proliferation and enhancing viability of HBMSCs. It is universally known that HBMSCs proliferation and viability are beneficial for tissue regeneration in bone or osteochondral lesions [ 29 , 30 ]. Therefore, PRP prepared from harvested blood and venous blood may have similar outcomes in spinal fusion.…”