Concise Review: Musculoskeletal Stem Cells to Treat Age-Related Osteoporosis

Stem cells translational medicine - Tập 6 Số 10 - Trang 1930-1939 - 2017
Jeffrey Kiernan1,2, John E. Davies2,3, William L. Stanford4,5
1aLaboratory Medicine Program, University Health Network, Toronto, Ontario, Canada
2bInstitute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada
3cFaculty of Dentistry, University of Toronto, Toronto, Ontario, Canada
4dSprott Centre for Stem Cell Research, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
5eDepartments of Cellular & Molecular Medicine, and Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada

Tóm tắt

Abstract Age-related (type-II) osteoporosis is a common and debilitating condition driven in part by the loss of bone marrow (BM) mesenchymal stromal cells (MSC) and their osteoblast progeny, leading to reduced bone formation. Current pharmacological regiments targeting age-related osteoporosis do not directly treat the disease by increasing bone formation, but instead use bisphosphonates to reduce bone resorption—a treatment designed for postmenopausal (type-I) osteoporosis. Recently, the bone regenerative capacity of MSCs has been found within a very rare population of skeletal stem cells (SSCs) residing within the larger heterogeneous BM-MSC pool. The osteoregenerative potential of SSCs would be an ideal candidate for cell-based therapies to treat degenerative bone diseases such as osteoporosis. However, to date, clinical and translational studies attempting to improve bone formation through cell transplantation have used the larger, nonspecific, MSC pool. In this review, we will outline the physiological basis of age-related osteoporosis, as well as discuss relevant preclinical studies that use exogenous MSC transplantation with the aim of treating osteoporosis in murine models. We will also discuss results from specific clinical trials aimed at treating other systemic bone diseases, and how the discovery of SSC could help realize the full regenerative potential of MSC therapy to increase bone formation. Finally, we will outline how ancillary clinical trials could be initiated to assess MSC/SSC-mediated bone formation gains in existing and potentially unrelated clinical trials, setting the stage for a dedicated clinical investigation to treat age-related osteoporosis.

Từ khóa


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Stem cells translational medicine

Tập 6 Số 10

1930-1939

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