Fate of mesenchymal stem cells transplanted to osteonecrosis of femoral head

Abstract

The purpose of this study was to investigate the survival and differentiation status of MSCs transplanted to ONFH. Traumatic ONFH was surgically produced in skeletally mature mongrel dogs. Osteonecrosis was treated with either saline (control) or autologous mesenchymal stem cells (MSCs) transplantation after decompression. Green fluorescent protein (GFP) was used to track the transplanted MSCs, the differentiation of MSCs were evaluated by fluorescent double-labeling with GFP between osteocalcin or von Willebrand factor (vWF) at 2nd, 8th, and 12th week after the transplantation. It was demonstrated that GFP-positive cells were present in the necrotic area up to 12 weeks after the transplantation, their number increased from 15% at 2nd week to 38% at 12th week (p < 0.05). Neither osteocalcin nor vWF was detected by immunocytochemistry in GFP-labeled MSCs in vitro, but osteocalcin was immunohistochemically positive in 90% of the GFP-labeled MSCs in vivo, while vWF was still negative. The vWF expression was of no significant difference between the control group and MSCs-transplanted group. The percentages of trabeculae bone volume were 9.36% and 8.42% at 2nd week (p > 0.05), 22.82% and 14.72% at 8th week, and 31.08% and 20.66% at 12th week (p < 0.05) in MSCs-transplanted group and control group, respectively; new trabeculae bone in MSCs-transplanted group was significantly increased as compared to that of control group at 8th and 12th week. The results demonstrated that the transplanted MSCs could survive, proliferate, and differentiate into osteoblasts directly, which contributed to the accelerated repair process. The possible mechanism is site-dependant differentiation. ß

Treatment of Osteonecrosis of the Femoral Head with VEGF₁₆₅ Transgenic Bone Marrow Mesenchymal Stem Cells in Mongrel Dogs

“…Recently, we confirmed the survival of BMSCs implanted into a canine model of ONFH and found that BMSCs in vivo demonstrated the differentiation characteristics of osteoblasts but not vascular endothelial cells [Yan et al, 2009].…”

“…Importantly, this procedure improved the blood supply of the cell implantation region, which contributed to the survival of implanted cells. Although we have identified the survival and primary differentiation of BMSCs in the area of ONFH of the same canine model [Yan et al, 2009], the exact mechanisms of such differentiation and the distribution of cells in necrotic areas remain largely unknown.…”

Cytotherapy of osteonecrosis of the femoral head: a mini review

“…The authors concluded that direct injection of autologous BMCs into femurs could prevent corticosteroid-induced ONFH following treatment with high-dose, short-term steroids. Yan et al [27] employed MSCs to treat ONFH and investigated the survival and differentiation status. Their research demonstrated that the transplanted MSCs could survive, proliferate and differentiate into osteoblasts directly, which could accelerate the repair process.…”

The role of “cell therapy” in osteonecrosis of the femoral head

“…Particular attention has been paid to multipotent mesenchymal stem cells (MSCs) and their ability to maintain mitotic multiplication while being capable of differentiating into various cellular types, such as osteoblasts, osteocytes, chondrocytes, and adipocytes (Baksh et al 2004). Experimentally, MSCs have been shown to enhance tissue regeneration when transplanted in areas of necrotic bone (Yan et al 2009). Various researchers have pioneered the clinical application of cell-based methods for the treatment of ONFH (Hernigou and Beaujean 2002, Gangji and Hauzeur 2005, Calori et al 2014).…”