Longer treatment period in distraction osteogenesis (DO) leads to more frequent complications. We developed a new technique of transplantation of culture expanded bone marrow cells (BMC) and platelet rich plasma (PRP) in DO of the long bones. Retrospective comparative study was conducted between the bones treated with and without BMC and PRP in DO to assess the efficacy of this new technique of transplantation. Ninety-two bones (46 patients) that were lengthened in our hospital and followed up until removal of the pins were divided into two groups according to the cell (BMC+PRP) treatment. The BMC-PRP(+) group consisted of 32 bones (14 femora, 18 tibiae) in 17 patients (10 boys and 7 girls), while the BMC-PRP(-) group consisted of 60 bones (25 femora, 35 tibiae) in 29 patients (13 boys and 16 girls). The clinical outcome including the age at operation, amount of length gained, the healing index, the delay in consolidation, and complications were compared between the two groups. The healing between the femoral and the tibial lengthening was also assessed. The average age at operation was 15.8 years in the BMC-PRP(+) group and 15.5 years in the BMC-PRP(-) group. Although there were no significant differences in the age at operation and the length gained between the two groups, the average healing indices of the BMC-PRP(+) group in short stature and in limb length discrepancy were significantly lower than those of the BMC-PRP(-) group (P=0.0019 and P=0.0031, respectively). A delay in consolidation was seen in 45% of the BMC-PRP(-) group but never observed in the BMC-PRP(+) group (P<0.0001). The rate of complications was 23% of the BMC-PRP(-) group and only 6% of the BMC-PRP(+) group (P=0.0406). The femoral lengthening showed significantly faster healing than the tibial lengthening by the BMC and PRP transplantation (P=0.0004) In conclusion, transplantation of BMC and PRP shortened the treatment period and reduced associated complications by accelerating new bone formation in DO.
"Enhanced callus formation was observed radiographically after first transplantation of marrow-derived mesenchymal stem cells and PLRG in all 3 cases. However, they applied a combination of two osteoinductive biomaterials and we do not know to what extent PLRG influenced bone formation in these cases . Our investigation showed that percutaneous L-PRP injection is a sufficient method to treat delayed union and is less invasive procedure than bone marrow injection. "
[Show abstract][Hide abstract] ABSTRACT: This article reports the efficacy of percutaneous autologous leukocyte-and platelet-rich plasma (L-PRP) injection into delayed union site as a minimally invasive method alternative to bone marrow aspirate and open grafting techniques. Each of 15 participants was followed on a regular basis with clinical examinations, roentgenograms. The average time to union was 8.4 weeks after L-PRP injection and the union was achieved in all cases. CD34+/45+ cells counts were increased by 410% and CD34+/45− cells counts were increased by 488% on average in L-PRP. Our investigation showed that L-PRP enrich in stem cells can produce the desired stimulatory response despite a substantial amount of vital bone cells from mesenchymal line. We believe that the using of L-PRP enriched in stem cells, growth factors and antimicrobial proteins might be a promising treatment method in regenerative medicine.
"     . Most of the clinical trials used autologous MSCs that were culture expanded   or bone marrow aspirate, concentrated using centrifugation  . Since MSCs were delivered with the intention to increase the pool of osteoprogenitor cells and not as agents to modulate immune cells, potential change induced by MSCs in the local microenvironment of immune cells was not considered in relation to bone healing. "
[Show abstract][Hide abstract] ABSTRACT: It is estimated that, of the 7.9 million fractures sustained in the United States each year, 5% to 20% result in delayed or impaired healing requiring therapeutic intervention. Following fracture injury, there is an initial inflammatory response that plays a crucial role in bone healing; however, prolonged inflammation is inhibitory for fracture repair. The precise spatial and temporal impact of immune cells and their cytokines on fracture healing remains obscure. Some cytokines are reported to be proosteogenic while others inhibit bone healing. Cell-based therapy utilizing mesenchymal stromal cells (MSCs) is an attractive option for augmenting the fracture repair process. Osteoprogenitor MSCs not only differentiate into bone, but they also exert modulatory effects on immune cells via a variety of mechanisms. In this paper, we review the current literature on both in vitro and in vivo studies on the role of the immune system in fracture repair, the use of MSCs in the enhancement of fracture healing, and interactions between MSCs and immune cells. Insight into this paradigm can provide valuable clues in identifying cellular and noncellular targets that can potentially be modulated to enhance both natural bone healing and bone repair augmented by the exogenous addition of MSCs.
Journal of Immunology Research 05/2015; 2015:1-17. DOI:10.1155/2015/752510 · 2.93 Impact Factor
"Notably, we frequently observed failed callus formation at the distal end of the gap, while that at the proximal end was less affected by the H-DO procedure. As described previously, engrafted MSCs, but not FBs, promoted callus formation in the H-DO gap    (Figs. 1D and E). However, immunohistochemical analysis with a human MHC class I-specific antibody (Fig. 1I) showed that the engrafted MSCs had disappeared from the DO gap by the end of the consolidation period (Fig. 1J), indicating that the engrafted MSCs accelerated callus formation by paracrine mechanisms. "
[Show abstract][Hide abstract] ABSTRACT: Distraction osteogenesis (DO) successfully induces large-scale skeletal tissue regeneration, but it involves an undesirably long treatment period. A high-speed DO mouse model (H-DO) with a distraction speed twice that of a control DO model failed to generate new bone callus in the distraction gap. Here we demonstrate that the local administration of serum-free conditioned medium from human mesenchymal stem cells (MSC-CM) accelerated callus formation in the mouse H-DO model. Secretomic analysis identified factors contained in MSC-CM that recruit murine bone marrow stromal cells (mBMSCs) and endothelial cells/endothelial progenitor cells (EC/EPCs), inhibit inflammation and apoptosis, and promote osteoblast differentiation, angiogenesis, and cell proliferation. Functional assays identified MCP-1/-3 and IL-3/-6 as essential factors in recruiting mBMSCs and EC/EPCs. IL-3/-6 also enhanced the osteogenic differentiation of mBMSCs. MSC-CM that had been depleted of MCP-1/-3 failed to recruit mBMSCs, and consequently failed to promote callus formation. Taken together, our data suggest that MSCs produce a broad repertoire of trophic factors with tissue-regenerative activities that accelerate healing in the DO process.
Bone 01/2014; 61. DOI:10.1016/j.bone.2013.12.029 · 3.97 Impact Factor
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