title: 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 UCB-MSCs (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.
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Jee Hyun
authors.initials: JH
authors.lastname: An
authors.forename: Hyojung
authors.initials: H
authors.lastname: Park
authors.forename: Jung Ah
authors.initials: JA
authors.lastname: Song
authors.forename: Kyung Ho
authors.initials: KH
authors.lastname: Ki
authors.forename: Jae-Yeon
authors.initials: JY
authors.lastname: Yang
authors.forename: Hyung Jin
authors.initials: HJ
authors.lastname: Choi
authors.forename: Sun Wook
authors.initials: SW
authors.lastname: Cho
authors.forename: Sang Wan
authors.initials: SW
authors.lastname: Kim
authors.forename: Seong Yeon
authors.initials: SY
authors.lastname: Kim
authors.forename: Jeong Joon
authors.initials: JJ
authors.lastname: Yoo
authors.forename: Wook-Young
authors.initials: WY
authors.lastname: Baek
authors.forename: Jung-Eun
authors.initials: JE
authors.lastname: Kim
authors.forename: Soo Jin
authors.initials: SJ
authors.lastname: Choi
authors.forename: Wonil
authors.initials: W
authors.lastname: Oh
authors.forename: Chan Soo
authors.initials: CS
authors.lastname: Shin
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000187:drug effects; D016723:Bone Remodeling / Q000187:drug effects; D001862:Bone Resorption / Q000097:blood / Q000473:pathology / Q000517:prevention & control* / Q000628:therapy*; D002454:Cell Differentiation / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D005260:Female; D005312:Fetal Blood / Q000166:cytology*; D005434:Flow Cytometry; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism; D010052:Ovariectomy; D011859:Radiography; D013131:Spine / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D013977:Tibia / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology
chemical_list: D015415:Biomarkers; D017077:Culture Media, Conditioned