PTH induces systemically administered mesenchymal stem cells to migrate to and regenerate spine injuries

Dmitriy Sheyn, Galina Shapiro, Wafa Tawackoli, Douk Soo Jun, Youngdo Koh, Kyu Bok Kang, Susan Su, Xiaoyu Da, Shiran Ben-David, Maxim Bez, Eran Yalon, Ben Antebi, Pablo Avalos, Tomer Stern, Elazar Zelzer, Edward M. Schwarz, Zulma Gazit, Gadi Pelled, Hyun M. Bae, Dan Gazit

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

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.

Original languageEnglish
Pages (from-to)318-330
Number of pages13
JournalMolecular Therapy
Volume24
Issue number2
DOIs
StatePublished - 1 Feb 2016

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