Format

Send to

Choose Destination
Mol Ther. 2016 Feb;24(2):318-330. doi: 10.1038/mt.2015.211. Epub 2015 Nov 20.

PTH Induces Systemically Administered Mesenchymal Stem Cells to Migrate to and Regenerate Spine Injuries.

Author information

1
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.
2
Skeletal Biotech Laboratory, Hebrew University of Jerusalem, Jerusalem, Israel.
3
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.
4
Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California, USA.
5
Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
6
Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
7
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
8
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.
9
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.
10
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.

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.

PMID:
26585691
PMCID:
PMC4817819
DOI:
10.1038/mt.2015.211
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center