Safety of intra-articular transplantation of lentivirally transduced mesenchymal stromal cells for haemophilic arthropathy in a non-human primate View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2018-05-08

AUTHORS

Tsukasa Ohmori, Hiroaki Mizukami, Yuko Katakai, Sho Kawai, Hitoyasu Nakamura, Makoto Inoue, Tsugumine Shu, Hideharu Sugimoto, Yoichi Sakata

ABSTRACT

Joint bleeding and resultant arthropathy are major determinants of quality of life in haemophilia patients. We previously developed a mesenchymal stromal cell (MSC)-based treatment approach for haemophilic arthropathy in a mouse model of haemophilia A. Here, we evaluated the long-term safety of intra-articular injection of lentivirally transduced autologous MSCs in non-human primates. Autologous bone-marrow-derived MSCs transduced with a lentiviral vector expressing coagulation factor VIII (FVIII) were injected into the left knee joint of cynomolgus monkeys. We first conducted codon optimization to increase FVIII production in the cells. Lentiviral transduction of autologous MSCs resulted in a significant increase of FVIII in the culture supernatant before transplantation. We did not find any tumour generation around the knee structure at 11–16 months after injection by magnetic resonance imaging. The proviral sequence of the simian immunodeficiency virus lentiviral vector was not detected in the heart, lungs, spleen, liver, testis, or bone marrow by real-time quantitative PCR. We confirmed the long-term safety of intra-articular injection of transduced MSCs in a non-human primate. The procedure may be an attractive therapeutic approach for joint diseases in haemophilia patients. More... »

PAGES

239-245

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s12185-018-2465-8

DOI

http://dx.doi.org/10.1007/s12185-018-2465-8

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1103859305

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/29737459


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