title: Feasibility and Efficacy of Autologous Bone Marrow Aspirate Transplantation Combined with Human Parathyroid Hormone 1-34 Administration to Treat Osteonecrosis in a Rabbit Model.
abstract: No studies have examined the transplantation of a bone marrow aspirate (BMA) containing mesenchymal stem cells (MSCs) combined with human parathyroid hormone 1-34 (hPTH1-34) administration. Therefore, we evaluated the feasibility and efficacy of autologous BMA transplantation combined with hPHT1-34 administration in a bone necrosis model. The metatarsal bones of rabbits were necrotized using liquid nitrogen, and the rabbits received a BMA transplantation or saline injection followed by hPTH1-34 (30μg/kg) or saline administration three times per week (n= 3-4 per group). The rabbits were euthanized at 12 weeks after the initiation of treatment. No systemic adverse effects or local neoplastic lesions were observed. Importantly, the rabbits in the BMA transplantation plus hPTH1-34 group showed the highest bone volumes and histological scores of new bone. These data confirmed the feasibility of BMA transplantation combined with hPTH1-34, at least during the experimental period. The observed efficacy may be explained by a synergistic effect from the stimulation of MSC differentiation to osteoblasts with hPTH1-34-mediated suppression of apoptosis in osteoblasts. These results indicate the promising potential for BMA transplantation combined with hPTH1-34 administration in bone necrosis treatment. Longer term experiments are needed to confirm the safety of this therapeutic strategy.
authors.affiliation: Department of Orthopedics Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Takeshi
authors.identifier: 0000-0001-8788-2867
authors.initials: T
authors.lastname: Makihara
authors.affiliation: Division of Regenerative Medicine for Musculoskeletal System, Department of Orthopedics Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Tomokazu
authors.identifier: 0000-0001-8687-4582
authors.initials: T
authors.lastname: Yoshioka
authors.affiliation: Division of Regenerative Medicine for Musculoskeletal System, Department of Orthopedics Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Sugaya
authors.affiliation: Department of Orthopedics Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Katsuya
authors.initials: K
authors.lastname: Aoto
authors.affiliation: Department of Orthopedics Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Hiroshi
authors.identifier: 0000-0002-7263-3232
authors.initials: H
authors.lastname: Wada
authors.affiliation: Department of Orthopedics Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Kenta
authors.initials: K
authors.lastname: Uemura
authors.affiliation: Department of Orthopedics Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Kenta
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Department of Orthopedics Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Akaogi
authors.affiliation: Department of Orthopedics Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Yamazaki
authors.affiliation: Department of Orthopedics Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Mishima