title: PTH Induces Systemically Administered Mesenchymal Stem Cells to Migrate to and Regenerate Spine Injuries.
abstract: Osteoporosis affects more than 200 million people worldwide leading to more than 2 million fractures in the United States alone. Unfortunately, surgical treatment is limited in patients with low bone mass. Parathyroid hormone (PTH) was shown to induce fracture repair in animals by activating mesenchymal stem cells (MSCs). However, it would be less effective in patients with fewer and/or dysfunctional MSCs due to aging and comorbidities. To address this, we evaluated the efficacy of combination i.v. MSC and PTH therapy versus monotherapy and untreated controls, in a rat model of osteoporotic vertebral bone defects. The results demonstrated that combination therapy significantly increased new bone formation versus monotherapies and no treatment by 2 weeks (P < 0.05). Mechanistically, we found that PTH significantly enhanced MSC migration to the lumbar region, where the MSCs differentiated into bone-forming cells. Finally, we used allogeneic porcine MSCs and observed similar findings in a clinically relevant minipig model of vertebral defects. Collectively, these results demonstrate that in addition to its anabolic effects, PTH functions as an adjuvant to i.v. MSC therapy by enhancing migration to heal bone loss. This systemic approach could be attractive for various fragility fractures, especially using allogeneic cells that do not require invasive tissue harvest.
authors.affiliation: Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California, USA; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
authors.forename: Dmitriy
authors.initials: D
authors.lastname: Sheyn
authors.affiliation: Skeletal Biotech Laboratory, Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Galina
authors.initials: G
authors.lastname: Shapiro
authors.affiliation: Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California, USA; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA; Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
authors.forename: Wafa
authors.initials: W
authors.lastname: Tawackoli
authors.affiliation: Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California, USA.
authors.forename: Douk Soo
authors.initials: DS
authors.lastname: Jun
authors.affiliation: Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California, USA.
authors.forename: Youngdo
authors.initials: Y
authors.lastname: Koh
authors.affiliation: Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California, USA.
authors.forename: Kyu Bok
authors.initials: KB
authors.lastname: Kang
authors.affiliation: Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California, USA; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Su
authors.affiliation: Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Da
authors.affiliation: Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California, USA; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
authors.forename: Shiran
authors.initials: S
authors.lastname: Ben-David
authors.affiliation: Skeletal Biotech Laboratory, Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Maxim
authors.initials: M
authors.lastname: Bez
authors.affiliation: Skeletal Biotech Laboratory, Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Eran
authors.initials: E
authors.lastname: Yalon
authors.affiliation: Skeletal Biotech Laboratory, Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Ben
authors.initials: B
authors.lastname: Antebi
authors.affiliation: Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
authors.forename: Pablo
authors.initials: P
authors.lastname: Avalos
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Tomer
authors.initials: T
authors.lastname: Stern
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Elazar
authors.initials: E
authors.lastname: Zelzer
authors.affiliation: The Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, New York, USA; Department of Orthopedics, University of Rochester Medical Center, Rochester, New York, USA.
authors.forename: Edward M
authors.initials: EM
authors.lastname: Schwarz
authors.affiliation: Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California, USA; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA; Skeletal Biotech Laboratory, Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Zulma
authors.initials: Z
authors.lastname: Gazit
authors.affiliation: Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California, USA; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA; Skeletal Biotech Laboratory, Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Gadi
authors.initials: G
authors.lastname: Pelled
authors.affiliation: Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California, USA.
authors.forename: Hyun M
authors.initials: HM
authors.lastname: Bae
authors.affiliation: Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California, USA; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA; Skeletal Biotech Laboratory, Hebrew University of Jerusalem, Jerusalem, Israel; Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA. Electronic address: dan.gazit@csmc.edu.
authors.forename: Dan
authors.initials: D
authors.lastname: Gazit
mesh_terms: D000818:Animals; D001861:Bone Regeneration / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects*; D010024:Osteoporosis / Q000150:complications / Q000628:therapy*; D010281:Parathyroid Hormone / Q000494:pharmacology*; D051381:Rats; D016103:Spinal Fractures / Q000209:etiology / Q000628:therapy*; D013552:Swine
chemical_list: D010281:Parathyroid Hormone