@article{cda464c31e26455f86e225a44816f5c4,
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.",
author = "Dmitriy Sheyn and Galina Shapiro and Wafa Tawackoli and Jun, {Douk Soo} and Youngdo Koh and Kang, {Kyu Bok} and Susan Su and Xiaoyu Da and Shiran Ben-David and Maxim Bez and Eran Yalon and Ben Antebi and Pablo Avalos and Tomer Stern and Elazar Zelzer and Schwarz, {Edward M.} and Zulma Gazit and Gadi Pelled and Bae, {Hyun M.} and Dan Gazit",
note = "Funding Information: The research was supported by grants from CIRM TR2-01780 and NIH (R01DE019902 and P50 AR054041). The teriparatide was a gift from Eli Lilly, Inc., Indianapolis, IN. D.S., G.S., W.T., E.M.S., Z.G., G.P., and D.G. contributed to the study concepts. W.T., D.S.J., and Y.K. performed small animal surgical procedures. W.T., D.S.J., Y.K., P.A., and H.M.B. performed large-animal experiments. X.D., G.S., M.B., E.Y., E.Z., and T.S. performed µCT imaging and data analysis. S.B.D., S.S., and D.S. were responsible for vector production, tissue staining, PCR, and microscopy. D.S., G.S., E.M.S. and G.P. wrote the manuscript. A provisional patent, assigned to Cedars-Sinai Medical Center and Rochester University, is pending. The authors declare no other competing financial interests. Funding Information: The research was supported by grants from CIRM TR2-01780 and NIH (R01DE019902 and P50 AR054041). The teriparatide was a gift from Eli Lilly, Inc., Indianapolis, IN. D.S., G.S., W.T., E.M.S., Z.G., G.P., and D.G. contributed to the study concepts. W.T., D.S.J., and Y.K. performed small animal surgical procedures. W.T., D.S.J., Y.K., P.A., and H.M.B. performed large-animal experiments. X.D., G.S., M.B., E.Y., E.Z., and T.S. performed μCT imaging and data analysis. S.B.D., S.S., and D.S. were responsible for vector production, tissue staining, PCR, and microscopy. D.S., G.S., E.M.S. and G.P. wrote the manuscript. A provisional patent, assigned to Cedars-Sinai Medical Center and Rochester University, is pending. The authors declare no other competing financial interests. Publisher Copyright: {\textcopyright} 2016 The American Society of Gene & Cell Therapy.",
year = "2016",
month = feb,
day = "1",
doi = "10.1038/mt.2015.211",
language = "English",
volume = "24",
pages = "318--330",
journal = "Molecular Therapy",
issn = "1525-0016",
publisher = "Cell Press",
number = "2",
}