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.
1525-0024 Sheyn, Dmitriy Shapiro, Galina Tawackoli, Wafa Jun, Douk Soo Koh, Youngdo Kang, Kyu Bok Su, Susan Da, Xiaoyu Ben-David, Shiran Bez, Maxim Yalon, Eran Antebi, Ben Avalos, Pablo Stern, Tomer Zelzer, Elazar Schwarz, Edward M Gazit, Zulma Pelled, Gadi Bae, Hyun M Gazit, Dan P50 AR054041/AR/NIAMS NIH HHS/United States R01 DE019902/DE/NIDCR NIH HHS/United States R01DE019902/DE/NIDCR NIH HHS/United States Comparative Study Journal Article Research Support, N.I.H., Extramural United States Mol Ther. 2016 Feb;24(2):318-330. doi: 10.1038/mt.2015.211. Epub 2015 Nov 20.