title: Rapid and efficient reprogramming of human fetal and adult blood CD34+ cells into mesenchymal stem cells with a single factor.
abstract: The direct conversion of skin cells into somatic stem cells has opened new therapeutic possibilities in regenerative medicine. Here, we show that human induced mesenchymal stem cells (iMSCs) can be efficiently generated from cord blood (CB)- or adult peripheral blood (PB)-CD34(+) cells by direct reprogramming with a single factor, OCT4. In the presence of a GSK3 inhibitor, 16% of the OCT4-transduced CD34(+) cells are converted into iMSCs within 2 weeks. Efficient direct reprogramming is achieved with both episomal vector-mediated transient OCT4 expression and lentiviral vector-mediated OCT4 transduction. The iMSCs express MSC markers, resemble bone marrow (BM)-MSCs in morphology, and possess in vitro multilineage differentiation capacity, yet have a greater proliferative capacity compared with BM-MSCs. Similar to BM-MSCs, the implanted iMSCs form bone and connective tissues, and are non-tumorigenic in mice. However, BM-MSCs do not, whereas iMSCs do form muscle fibers, indicating a potential functional advantage of iMSCs. In addition, we observed that a high level of OCT4 expression is required for the initial reprogramming and the optimal iMSC self-renewal, while a reduction of OCT4 expression is required for multilineage differentiation. Our method will contribute to the generation of patient-specific iMSCs, which could have applications in regenerative medicine. This discovery may also facilitate the development of strategies for direct conversion of blood cells into other types of cells of clinical importance.
authors.affiliation: Division of Regenerative Medicine MC1528B, Department of Medicine, Loma Linda University, Loma Linda, CA 92354, USA.
authors.forename: Xianmei
authors.initials: X
authors.lastname: Meng
authors.forename: Rui-Jun
authors.initials: RJ
authors.lastname: Su
authors.forename: David J
authors.initials: DJ
authors.lastname: Baylink
authors.forename: Amanda
authors.initials: A
authors.lastname: Neises
authors.forename: Jason B
authors.initials: JB
authors.lastname: Kiroyan
authors.forename: Wayne Yuk-Wai
authors.initials: WY
authors.lastname: Lee
authors.forename: Kimberly J
authors.initials: KJ
authors.lastname: Payne
authors.forename: Daila S
authors.initials: DS
authors.lastname: Gridley
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: K-H William
authors.initials: KH
authors.lastname: Lau
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.forename: Xiao-Bing
authors.initials: XB
authors.lastname: Zhang
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism*; D001773:Blood Cells / Q000166:cytology* / Q000378:metabolism; D001842:Bone and Bones / Q000473:pathology; D002454:Cell Differentiation; D002478:Cells, Cultured; D065150:Cellular Reprogramming; D003238:Connective Tissue / Q000473:pathology; D005312:Fetal Blood / Q000166:cytology* / Q000378:metabolism; D005822:Genetic Vectors / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D007621:Karyotyping; D016086:Lentivirus / Q000235:genetics; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism*; D014161:Transduction, Genetic
chemical_list: D018952:Antigens, CD34; D050814:Octamer Transcription Factor-3; D038362:Glycogen Synthase Kinase 3