title: Human bone marrow stem cells cultured under hypoxic conditions present altered characteristics and enhanced in vivo tissue regeneration.
abstract: Human bone marrow mesenchymal stem cells (hBMSCs) were isolated from bone marrow of the vertebral body. The hBMSCs were cultured under either hypoxic (1% O2) or normoxic (21% O2; control) conditions and the characteristics as mesenchymal stem cells were compared. Results revealed that hypoxia reduced proliferative potential and colony-forming efficiency of hBMSCs, and significantly enhanced osteogenic and chondrogenic differentiation. The hBMSCs enhanced the regenerative potential of bone in vivo. In vitro synthesis of soluble and insoluble collagen was significantly increased in the hypoxic condition. In vivo collagen tissue regeneration was also enhanced under the hypoxic condition, with concomitant increased expressions of various subtypes of collagen and lysyl-oxidase family mRNA. MicroRNA assays revealed that miR-155-5p, which negatively regulates HIF-1α, was significantly highly expressed. These observations demonstrate that hBMSCs obtained from human vertebrae exhibit altered characteristics under hypoxic conditions, and each factor contributing to hBMSC-mediated tissue healing should be evaluated with the goal of allowing their clinical application.
authors.affiliation: Department of Periodontology, Research Institute for Periodontal Regeneration, College of Dentistry, Yonsei University, Seoul, Republic of Korea. Electronic address: cooldds@gmail.com.
authors.forename: Jung-Seok
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Department of Periodontology, College of Dentistry, Dankook University, Cheonan, Republic of Korea. Electronic address: yonseimagic@gmail.com.
authors.forename: Jung-Chul
authors.initials: JC
authors.lastname: Park
authors.affiliation: Department of Periodontology, Research Institute for Periodontal Regeneration, College of Dentistry, Yonsei University, Seoul, Republic of Korea. Electronic address: ikale2@naver.com.
authors.forename: Tae-Wan
authors.initials: TW
authors.lastname: Kim
authors.affiliation: Naeun Hospital, Neurosurgery, Seoul, Republic of Korea. Electronic address: wishbj@gmail.com.
authors.forename: Byung-Joo
authors.initials: BJ
authors.lastname: Jung
authors.affiliation: Department of Bio and Fermentation Convergence Technology, Kookmin University, Seoul, Republic of Korea. Electronic address: iven1125@gmail.com.
authors.forename: Youngseok
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Biomedical Research Institute, iBMT, Anyang, Republic of Korea. Electronic address: eun-karma@hanmail.net.
authors.forename: Eun-Kyung
authors.initials: EK
authors.lastname: Shim
authors.affiliation: Department of Periodontology, Research Institute for Periodontal Regeneration, College of Dentistry, Yonsei University, Seoul, Republic of Korea. Electronic address: soyonp@yuhs.ac.
authors.forename: Soyon
authors.initials: S
authors.lastname: Park
authors.affiliation: Department of Periodontology, Research Institute for Periodontal Regeneration, College of Dentistry, Yonsei University, Seoul, Republic of Korea. Electronic address: perioheal@yuhs.ac.
authors.forename: Eun-Young
authors.initials: EY
authors.lastname: Choi
authors.affiliation: Department of Periodontology, Research Institute for Periodontal Regeneration, College of Dentistry, Yonsei University, Seoul, Republic of Korea. Electronic address: kscho@yuhs.ac.
authors.forename: Kyoo-Sung
authors.initials: KS
authors.lastname: Cho
authors.affiliation: Department of Periodontology, Research Institute for Periodontal Regeneration, College of Dentistry, Yonsei University, Seoul, Republic of Korea; Department of Applied Life Science, BK21 PLUS Project, College of Dentistry, Yonsei University, Seoul, Republic of Korea. Electronic address: dentall@yuhs.ac.
authors.forename: Chang-Sung
authors.initials: CS
authors.lastname: Kim
mesh_terms: D017667:Adipocytes / Q000166:cytology; D000328:Adult; D001854:Bone Marrow Cells / Q000166:cytology*; D002454:Cell Differentiation; D015687:Cell Hypoxia; D049109:Cell Proliferation; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology; D020219:Chondrogenesis; D003094:Collagen / Q000737:chemistry; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D035683:MicroRNAs / Q000378:metabolism; D008875:Middle Aged; D010012:Osteogenesis; D010100:Oxygen / Q000737:chemistry; D012038:Regeneration / Q000502:physiology*; D013131:Spine / Q000166:cytology; D013234:Stem Cells; D014945:Wound Healing
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C524942:MIRN155 microRNA, human; D035683:MicroRNAs; D003094:Collagen; D010100:Oxygen
keywords: Hypoxia; Mesenchymal stem cells; Stem cell microenvironment interactions; Tissue regeneration