Mesenchymal stem cell (MSC) therapy has emerged as a potentially powerful tool for osteochondral
repair, but the safety of stem cells in vivo is still not clear. In this study, we assessed the safety and efficacy of canine
adipose tissue-derived MSCs (cATMSCs) or umbilical cord blood-derived MSCs (cUCBMSCs) in osteochondral
repair. The test cells were implanted at the site of an osteochondral defect surgically created on the trochlear groove
of beagle dogs. To address safety concerns in this model, we conducted a GLP-compliant study. We observed no
significant treatment-related changes in body weights, clinical signs, food consumption, hematological or biochemical
values, organ weights, or histopathological findings. The stem cell implants induced no detectable tumor formation
or local or systemic rejection reaction. In the assessment of effectiveness, 13-week samples from both the
cATMSC- and cUCBMSC-implanted groups showed fibrous tissue formation in the extracellular matrix scaffold of
the defect similar to that of controls. However, repaired tissues in stem cell-seeded groups showed partial differentiation
toward an osteochondral phenotype. These findings support the safety of cATMSC or cUCBMSC transplantation,
and show that the cells may potentially differentiate into osteochondral tissues in our canine model. Our study
provides a framework in which to establish preclinical safety standards for the development of cellular therapeutics.