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No cell-related safety issues were encountered in this trial, although the patients receiving 18*10 6 MSCs showed a higher incidence of adverse effects ( Lastly, several human growth factor-based phase I/II clinical trials were started to evaluate the safety, tolerability, and preliminary effectiveness of intradiscal delivery of growth and differentiation factor-5 (GDF-5) as compared with placebo (sterile water/vehicle control) in human patients with early lumbar disc degeneration in the United States, Australia, and the Republic of Korea