Considerations in modern regenerative medicine for osteoarthritis.

Current non-surgical managements of osteoarthritis (OA) do not change the clinical course or arrest the progression of the disease, while joint replacement is indicated for end-stage disease. Given these limitations, there is an unmet clinical demand for new treatment modalities that can improve the pain and quality of life of patients suffering from OA without surgery. The recent surge of interest in regenerative medicine (RM) for OA is based on these circumstances. Unlike traditional medicine, RM products may be accompanied by many uncertainties and long-term consequences. Considering that OA directly affects quality of life rather than life and death, the 'first do no harm' principle is more important when applying RM technology to the disease. Presently, culture-expanded mesenchymal stromal cells (MSCs) and orthobiologics, including bone marrow aspirate concentrate, stromal vascular fraction from adipose tissue and platelet-rich plasma have been applied to patients in clinical trials. Results of randomized clinical trials using MSCs have demonstrated that structural improvement and reversal of the pathologic process in OA are not definitely shown, while symptomatic relief is apparent. Orthobiologics seem to have efficiency comparable to those of culture-expanded MSCs. With the advantage of avoiding the approval process from regulation agencies, orthobiologics might provide a less expensive and handier option to culture-expanded MSCs. High-quality data from a large number of patients and head-to-head comparisons of several RM products will be necessary to define the place of culture-expanded MSCs or orthobiologics for OA treatment and resolve the reimbursement issue.