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

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 ge...

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Bibliographic Details
Published in:Human & experimental toxicology 2023-01, Vol.42, p.9603271231171650-9603271231171650
Main Authors: Park, Sang-Jin, Kim, Dae Seong, Choi, Myeongjin, Han, Kang-Hyun, Han, Ji-Seok, Yoo, Keon Hee, Moon, Kyoung-Sik
Format: Article
Language:English
Subjects:
Adenoma
Animals
Antibodies
Biodistribution
Cell Differentiation
Cell Proliferation
Cell therapy
Cells, Cultured
Female
Humans
Immune clearance
Interferon
Interferon-gamma
Male
Mesenchymal stem cells
Mesenchymal Stem Cells - metabolism
Mice
Polymerase chain reaction
Stem cells
Tissue Distribution
Toxicity
Tumorigenicity
Tumors
Wharton Jelly - metabolism
γ-Interferon
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Summary: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.
ISSN:0960-3271
1477-0903
DOI:10.1177/09603271231171650