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The use of perinatal-derived tissues and mesenchymal stromal cells (MSCs) as alternative treatment options to corticosteroid and hyaluronic acid injections has been gaining popularity. However, their ability to attenuate osteoarthritic (OA) symptoms while also slowing the progression of the disease remains controversial. Thus, the objective of this article is to summarize the results from both preclinical and clinical studies evaluating the efficacy of perinatal-derived tissue allografts and MSCs for the treatment of OA.