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A wide array of treatment, both surgical and nonsurgical, exists for osteoarthritis (OA) of the knee. Injectable stem-cell therapy represents a minimally invasive and potentially efficacious treatment; however, there have been no level I studies conducted on this specific application of stem-cell therapy. The purpose of our review was to analyze, report, and summarize current topical data.A systematic review of the treatment of human knee OA with mesenchymal stem cells (MSCs) was performed by searching PubMed/Medline and Google Scholar. Non-human studies and studies involving additional procedures were excluded. Authors reviewed the studies individually, with the primary author deciding on inclusion.Our search ultimately returned 10 studies that met the inclusion criteria. Nine of the ten studies used cultured autologous MSCs, five from bone marrow, three from subcutaneous fat, and one from peripheral blood. The remaining study used allogenic bone marrow MSCs. Radiographic analysis of cartilage quality via MRI T2 mapping showed increased type II collagen production in five studies. Outcome scores consistently showed pain reduction and improved function. No study reported significant adverse events related to stem-cell therapy.Current human studies evaluating the use of injected MSCs for knee OA demonstrated consistent improvement across several outcome scores, with no significant adverse findings.Level IV, systematic review of Level II-IV trials and studies.