Transplantation of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells or Their Conditioned Medium Prevents Bone Loss in Ovariectomized Nude Mice

Abstract

Umbilical cord blood (UCB) has recently been recognized as a new source of mesenchymal stem cells (MSCs) for use in stem cell therapy. We studied the effects of systemic injection of human UCB-MSCs and their conditioned medium (CM) on ovariectomy (OVX)-induced bone loss in nude mice. Ten-week-old female nude mice were divided into six groups: Sham-operated mice treated with vehicle (Sham-Vehicle), OVX mice subjected to UCBMSCs (OVX-MSC), or human dermal fibroblast (OVX-DFB) transplantation, OVX mice treated with UCB-MSC CM (OVX-CM), zoledronate (OVX-Zol), or vehicle (OVX-Vehicle). Although the OVX-Vehicle group exhibited significantly less bone mineral density (BMD) gain compared with the Sham-Vehicle group, transplantation of hUCB-MSCs (OVX-MSC group) has effectively prevented OVX-induced bone mass attenuation. Notably, the OVX-CM group also showed BMD preservation comparable to the OVX-MSC group. In addition, microcomputed tomography analysis demonstrated improved trabecular parameters in both the OVX-MSC and OVX-CM groups compared to the OVX-Vehicle or OVX-DFB group. Histomorphometric analysis showed increased bone formation parameters, accompanied by increased serum procollagen type-I N-telopeptide levels in OVX-MSC and OVX-CM mice. However, cell-trafficking analysis failed to demonstrate engraftment of MSCs in bone tissue 48 h after cell infusion. In vitro, hUCB-MSC CM increased alkaline phosphatase (ALP) activity in human bone marrow-derived MSCs and mRNA expression of collagen type 1, Runx2, osterix, and ALP in C3H10T1/2 cells. Furthermore, hUCB-MSC CM significantly increased survival of osteocyte-like MLO-Y4 cells, while it inhibited osteoclastic differentiation. To summarize, transplantation of hUCB-MSCs could effectively prevent OVX-mediated bone loss in nude mice, which appears to be mediated by a paracrine mechanism rather than direct engraftment of the MSCs.

Stem Cell Interventions for Bone Healing: Fractures and Osteoporosis

“…An et al, demonstrated a 30% increase in bone mineral density (BMD) when human UBC-MSCs were injected in OVX mice after 4 and 8 weeks. They also observed increases in trabecular volume, number and thickness in OVX mice treated with hUB-MSCs [101].…”

Osteoporosis and the Potential of Cell-Based Therapeutic Strategies

“…Bone formation by umbilical cord-derived MSCs (UC-MSCs) was demonstrated in vivo by Diao and collaborators who loaded human UC-MSCs into scaffolds that were transplanted subcutaneously into BALB/c nude mice, observing efficiently bone formation by UC-MSCs [159]. [160] used OVX nude mice as a model to study the influence of systemic injection of human umbilical cord blood hUCB-MSCs. After the infusion, the BMD levels enhanced considerably and the micro-CT analysis of the mice tibiae exhibited considerably greater values of trabecular number and thickness, as well as bone volume.…”

Prospect of mesenchymal stem cells in therapy of osteoporosis: A review

“…In this study, human UC‐MSCs can proficiently form bone after transplantation in 12 weeks. An et al () studied the influence of systemic injection of umbilical cord blood (UCB)‐MSCs to OVX mice. Four and 8 weeks after the infusion, the BMD levels enhanced considerably.…”