title: Systemic Administration of Allogeneic Mesenchymal Stem Cells Does Not Halt Osteoporotic Bone Loss in Ovariectomized Rats.
abstract: Mesenchymal stem cells (MSCs) have innate ability to self-renew and immunosuppressive functions, and differentiate into various cell types. They have become a promising cell source for treating many diseases, particular for bone regeneration. Osteoporosis is a common metabolic bone disorder with elevated systemic inflammation which in turn triggers enhanced bone loss. We hypothesize that systemic infusion of MSCs may suppress the elevated inflammation in the osteoporotic subjects and slow down bone loss. The current project was to address the following two questions: (1) Will a single dose systemic administration of allogenic MSCs have any effect on osteoporotic bone loss? (2) Will multiple administration of allogenic MSCs from single or multiple donors have similar effect on osteoporotic bone loss? 18 ovariectomized (OVX) rats were assigned into 3 groups: the PBS control group, MSCs group 1 (receiving 2x106 GFP-MSCs at Day 10, 46, 91 from the same donor following OVX) and MSCs group 2 (receiving 2x106 GFP-MSCs from three different donors at Day 10, 46, 91). Examinations included Micro-CT, serum analysis, mechanical testing, immunofluorescence staining and bone histomorphometry analysis. Results showed that BV/TV at Day 90, 135, BMD of TV and trabecular number at Day 135 in the PBS group were significantly higher than those in the MSCs group 2, whereas trabecular spacing at Day 90, 135 was significantly smaller than that in MSCs group 2. Mechanical testing data didn't show significant difference among the three groups. In addition, the ELISA assay showed that level of Rantes in serum in MSCs group 2 was significantly higher than that of the PBS group, whereas IL-6 and IL-10 were significantly lower than those of the PBS group. Bone histomorphometry analysis showed that Oc.S/BS and Oc.N/BS in the PBS group were significant lower than those in MSCs group 2; Ob.S/BS and Ob.N/BS did not show significant difference among the three groups. The current study demonstrated that systemic administration of allogenic MSCs had no obvious effect on osteoporotic bone loss in OVX rats when using the cells from the same donor; and repeated injection of allogeneic MSCs from different donors might promote bone loss in OVX rats. These findings indicate that despite allogenic MSCs systemic infusion is safe, their administration alone may not be an effective mean for preventing osteoporotic bone loss.
authors.affiliation: Department of Rehabilitation Medicine, Center of Bone Metabolism and Repair, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, PR China.|Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, PR China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Huang
authors.affiliation: Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, PR China.|Stem Cells and Regenerative Medicine Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, PR China.|The CUHK-ACC Space Medicine Centre on Health Maintenance of Musculoskeletal System, The Chinese University of Hong Kong Shenzhen Research Institute, Shenzhen, PR China.
authors.forename: Liangliang
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, PR China.|Stem Cells and Regenerative Medicine Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, PR China.
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, PR China.|Stem Cells and Regenerative Medicine Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, PR China.|The CUHK-ACC Space Medicine Centre on Health Maintenance of Musculoskeletal System, The Chinese University of Hong Kong Shenzhen Research Institute, Shenzhen, PR China.
authors.forename: Sien
authors.initials: S
authors.lastname: Lin
authors.affiliation: The Orthopaedic Research Laboratory, Changzhou Seventh People's Hospital, Changzhou, Jiangshu Province, PR China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Gu
authors.affiliation: College of Fundamental Medical Sciences, Guang Zhou University of Traditional Chinese Medicine, Guang Zhou, PR China.
authors.forename: Yamei
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, PR China.
authors.forename: Jinfang
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Rehabilitation Medicine, Center of Bone Metabolism and Repair, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, PR China.
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, PR China.|Stem Cells and Regenerative Medicine Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, PR China.|The CUHK-ACC Space Medicine Centre on Health Maintenance of Musculoskeletal System, The Chinese University of Hong Kong Shenzhen Research Institute, Shenzhen, PR China.
authors.forename: Gang
authors.initials: G
authors.lastname: Li
mesh_terms: D000818:Animals; D000071556:Cancellous Bone / Q000000981:diagnostic imaging / Q000503:physiopathology; D016207:Cytokines / Q000097:blood; D005260:Female; D007267:Injections; D045164:Mesenchymal Stem Cell Transplantation; D010024:Osteoporosis / Q000097:blood / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000628:therapy*; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D014184:Transplantation, Homologous; D055114:X-Ray Microtomography
chemical_list: D016207:Cytokines