title: Efficient differentiation of human pluripotent stem cells into functional CD34+ progenitor cells by combined modulation of the MEK/ERK and BMP4 signaling pathways.
abstract: Differentiation of human pluripotent stem cells (hPSCs) into functional cell types is a crucial step in cell therapy. In the present study, we demonstrate that functional CD34(+) progenitor cells can be efficiently produced from human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) by combined modulation of 2 signaling pathways. A higher proportion of CD34(+) cells (∼ 20%) could be derived from hPSCs by inhibition of mitogen-activated protein kinase (MAPK) extracellular signal-regulated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling and activation of bone morphogenic protein-4 (BMP4) signaling. hPSC-derived CD34(+) progenitor cells further developed to endothelial and smooth muscle cells with functionality. Moreover, they contributed directly to neovasculogenesis in ischemic mouse hind limbs, thereby resulting in improved blood perfusion and limb salvage. Our results suggest that combined modulation of signaling pathways may be an efficient means of differentiating hPSCs into functional CD34(+) progenitor cells.
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.
authors.forename: Sang-Wook
authors.initials: SW
authors.lastname: Park
authors.forename: Young
authors.initials: Y
authors.lastname: Jun Koh
authors.forename: Jongwook
authors.initials: J
authors.lastname: Jeon
authors.forename: Yun-Hee
authors.initials: YH
authors.lastname: Cho
authors.forename: Mi-Jin
authors.initials: MJ
authors.lastname: Jang
authors.forename: Yujung
authors.initials: Y
authors.lastname: Kang
authors.forename: Min-Jeong
authors.initials: MJ
authors.lastname: Kim
authors.forename: Chulhee
authors.initials: C
authors.lastname: Choi
authors.forename: Yee
authors.initials: Y
authors.lastname: Sook Cho
authors.forename: Hyung-Min
authors.initials: HM
authors.lastname: Chung
authors.forename: Gou Young
authors.initials: GY
authors.lastname: Koh
authors.forename: Yong-Mahn
authors.initials: YM
authors.lastname: Han
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism*; D015153:Blotting, Western; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism*; D005434:Flow Cytometry; D006614:Hindlimb / Q000098:blood supply / Q000378:metabolism; D007124:Immunoenzyme Techniques; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism*; D007511:Ischemia / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics / Q000378:metabolism*; D018919:Neovascularization, Physiologic; D039904:Pluripotent Stem Cells / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: D018952:Antigens, CD34; C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D012333:RNA, Messenger; D048049:Extracellular Signal-Regulated MAP Kinases; D020929:Mitogen-Activated Protein Kinase Kinases