Preclinical Evaluation of interferon-gamma primed human Wharton's jelly-derived mesenchymal stem cells.

Park, Sang-Jin; Kim, Dae Seong; Choi, Myeongjin; Han, Kang-Hyun; Han, Ji-Seok; Yoo, Keon Hee; Moon, Kyoung-Sik

The potential of human mesenchymal stem cells (MSCs) for cell therapy has been investigated in numerous immune-mediated conditions; MSCs are considered one of the most promising cellular therapeutics to treat intractable diseases. Recently, approaches to prime MSCs have been investigated, thereby generating cellular products with enhanced potential for a variety of clinical applications. Interferon-gamma (IFN-γ) priming is a current approach used to increase the therapeutic efficacy of MSCs. In this study, we determined the systemic toxicity, tumorigenicity and biodistribution of IFN-γ-primed Wharton's jelly-derived (WJ)-MSCs in male and female BALB/c-nu/nu mice. There were no deaths or pathologic lesions in the mice treated with 5 × 106 cells/kg IFN-γ-primed MSCs in the repeated dose study. In the tumorigenicity study, one of the subcutaneously treated mice showed bronchioloalveolar adenoma in the lung but tested negative for human-specific anti-mitochondrial antibody, suggesting the spontaneous murine origin of the adenoma. A biodistribution study using real-time quantitative polymerase chain reaction demonstrated the systemic IFN-γ-primed MSC clearance by day 28. Based on the toxicity, biodistribution, and tumorigenicity studies, we concluded that IFN-γ-primed MSCs at 5 × 106 cells/kg do not induce tumor formation and adverse changes.

DRUG dosage; CELLULAR therapy; ANIMAL experimentation; INTERFERONS; TREATMENT effectiveness; TOXICITY testing; POLYMERASE chain reaction; MESENCHYMAL stem cells; MICE; DRUG toxicity

Human & Experimental Toxicology, 2023, Vol 42, p1

0960-3271

Academic Journal

10.1177/09603271231171650