[논문]Improving the Safety of Mesenchymal Stem Cell-Based Ex Vivo Therapy Using Herpes Simplex Virus Thymidine Kinase

Bashyal, Narayan; Lee, Tae-Young; Chang, Da-Young; Jung, Jin-Hwa; Kim, Min Gyeong; Acharya, Rakshya; Kim, Sung-Soo; Oh, Il-Hoan; Suh-Kim, Haeyoung

doi:10.14348/molcells.2022.5015

[국내논문] Improving the Safety of Mesenchymal Stem Cell-Based Ex Vivo Therapy Using Herpes Simplex Virus Thymidine Kinase 원문보기

Molecules and cells, v.45 no.7, 2022년, pp.479 - 494

Bashyal, Narayan (Department of Anatomy, Ajou University School of Medicine) , Lee, Tae-Young (Research Center, Cell&Brain Co., Ltd.) , Chang, Da-Young (Research Center, Cell&Brain Co., Ltd.) , Jung, Jin-Hwa (Department of Anatomy, Ajou University School of Medicine) , Kim, Min Gyeong (Department of Anatomy, Ajou University School of Medicine) , Acharya, Rakshya (Department of Anatomy, Ajou University School of Medicine) , Kim, Sung-Soo (Department of Anatomy, Ajou University School of Medicine) , Oh, Il-Hoan (Department of Medical Lifescience, The Catholic University of Korea, College of Medicine) , Suh-Kim, Haeyoung (Department of Anatomy, Ajou University School of Medicine)

Abstract ▼ AI-Helper

Human mesenchymal stem cells (MSCs) are multipotent stem cells that have been intensively studied as therapeutic tools for a variety of disorders. To enhance the efficacy of MSCs, therapeutic genes are introduced using retroviral and lentiviral vectors. However, serious adverse events (SAEs) such as tumorigenesis can be induced by insertional mutagenesis. We generated lentiviral vectors encoding the wild-type herpes simplex virus thymidine kinase (HSV-TK) gene and a gene containing a point mutation that results in an alanine to histidine substitution at residue 168 (TK(A168H)) and transduced expression in MSCs (MSC-TK and MSC-TK(A168H)). Transduction of lentiviral vectors encoding the TK(A168H) mutant did not alter the proliferation capacity, mesodermal differentiation potential, or surface antigenicity of MSCs. The MSC-TK(A168H) cells were genetically stable, as shown by karyotyping. MSC-TK(A168H) responded to ganciclovir (GCV) with an half maximal inhibitory concentration (IC50) value 10-fold less than that of MSC-TK. Because MSC-TK(A168H) cells were found to be non-tumorigenic, a U87-TK(A168H) subcutaneous tumor was used as a SAE-like condition and we evaluated the effect of valganciclovir (vGCV), an oral prodrug for GCV. U87-TK(A168H) tumors were more efficiently ablated by 200 mg/kg vGCV than U87-TK tumors. These results indicate that MSC-TK(A168H) cells appear to be pre-clinically safe for therapeutic use. We propose that genetic modification with HSV-TK(A168H) makes allogeneic MSC-based ex vivo therapy safer by eliminating transplanted cells during SAEs such as uncontrolled cell proliferation.

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저장형식	Text(ASCII format) Excel format RefWorks Direct Export RIS format (for Reference Manager, ProCite, EndNote), Scholar's Aids, Mendeley
메일정보	받는사람 (필수) @ 보내는사람 (선택) @ 제목 내용 KISTI 검색결과 이메일 서비스
안내	총 건의 자료가 검색되었습니다. 다운받으실 자료의 인덱스를 입력하세요. (1-10,000) 검색결과의 순서대로 최대 10,000건 까지 다운로드가 가능합니다. 데이타가 많을 경우 속도가 느려질 수 있습니다.(최대 2~3분 소요) 다운로드 파일은 UTF-8 형태로 저장됩니다. 파일의 내용이 제대로 보이지 않을실 때는 웹브라우저 상단의 보기 -> 인코딩 -> 자동선택 여부를 확인하십시오. ~ Text(ASCII format) Excel format

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