title: Umbilical cord blood-derived non-hematopoietic stem cells retrieved and expanded on bone marrow-derived extracellular matrix display pluripotent characteristics.
abstract: Umbilical cord blood (UCB) not only contains hematopoietic stem cells (HSCs), but also non-hematopoietic stem cells (NHSCs) that are able to differentiate into a number of distinct cell types. Based on studies published to date, the frequency of NHSCs in UCB is believed to be very low. However, the isolation of these cells is primarily based on their adhesion to tissue culture plastic surfaces.
  
  
  
  In the current study, we demonstrate that this approach overlooks some of the extremely immature NHSCs because they lack the ability to adhere to plastic. Using a native extracellular matrix (ECM), produced by bone marrow (BM) stromal cells, the majority of the UCB-NHSCs attached within 4 h. The colony-forming unit fibroblast frequency of these cells was 1.5 × 104/108mononuclear cells, which is at least 4000-fold greater than previously reported for UCB-NHSCs. The phenotype of these cells was fibroblast-like and different from those obtained by plastic adhesion; they formed embryonic body-like clusters that were OCT4-positive and expressed other human embryonic stem cell-related markers. Importantly, when implanted subcutaneously for 8 weeks into immunocompromised mice, these ECM-adherent and expanded NHSCs generated three germ layer-derived human tissues including muscle, fat, blood vessel, bone, gland, and nerve. Moreover, injection of these cells into muscle damaged by cryoinjury significantly accelerated muscle regeneration.
  
  
  
  These results indicate that UCB may be a virtually unlimited source of NHSCs when combined with isolation and expansion on ECM. NHSCs may be a practical alternative to embryonic stem cells for a number of therapeutic applications.
authors.affiliation: Research Division, Department of Comprehensive Dentistry, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229-3900, USA.|Department of Orthodontics, Fourth Military Medical University, School of Stomatology, Xi'an, Shaanxi Province, 710032, People's Republic of China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Wu
authors.affiliation: Research Division, Department of Comprehensive Dentistry, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229-3900, USA.|Center for Reproductive Medicine, Ren-Ji Hospital, School of Medicine, Shanghai Jiao-Tong University, Shanghai, 200135, People's Republic of China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Research Division, Department of Comprehensive Dentistry, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229-3900, USA.|Department of Biomedical Engineering, University of Texas at San Antonio, San Antonio, TX, 78249, USA.
authors.forename: Travis J
authors.initials: TJ
authors.lastname: Block
authors.affiliation: Research Division, Department of Comprehensive Dentistry, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229-3900, USA.|Department of Biomedical Engineering, University of Texas at San Antonio, San Antonio, TX, 78249, USA.
authors.forename: Milos
authors.initials: M
authors.lastname: Marinkovic
authors.affiliation: Research Division, Department of Comprehensive Dentistry, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229-3900, USA.|Department of Plastic Surgery, Ren-Ji Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Zhi-Liang
authors.initials: ZL
authors.lastname: Zhang
authors.affiliation: Research Division, Department of Comprehensive Dentistry, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229-3900, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Chen
authors.affiliation: Research Division, Department of Comprehensive Dentistry, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229-3900, USA.|Biomedical Materials Engineering Research Center, Wuhan University of Technology, Wuhan, People's Republic of China.
authors.forename: Yixia
authors.initials: Y
authors.lastname: Yin
authors.affiliation: Department of Surgery, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229-3900, USA.
authors.forename: Juquan
authors.initials: J
authors.lastname: Song
authors.affiliation: Research Division, Department of Comprehensive Dentistry, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229-3900, USA.|Department of Biomedical Engineering, University of Texas at San Antonio, San Antonio, TX, 78249, USA.
authors.forename: David D
authors.initials: DD
authors.lastname: Dean
authors.affiliation: Research Division, Department of Comprehensive Dentistry, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229-3900, USA. xwdlu@yahoo.com.
authors.forename: Zhongding
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Research Division, Department of Comprehensive Dentistry, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229-3900, USA. chenx4@uthscsa.edu.|Research Service, Audie L. Murphy Division, South Texas Veterans Health Care System, San Antonio, TX, 78229-4404, USA. chenx4@uthscsa.edu.
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Chen
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D051929:CD146 Antigen / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion; D002478:Cells, Cultured; D058732:Embryoid Bodies / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D005109:Extracellular Matrix / Q000737:chemistry* / Q000378:metabolism; D005312:Fetal Blood / Q000166:cytology / Q000378:metabolism; D015870:Gene Expression; D005855:Germ Layers / Q000166:cytology* / Q000254:growth & development / Q000378:metabolism; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000293:injuries; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D012038:Regeneration / Q000235:genetics*; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
chemical_list: D015415:Biomarkers; D051929:CD146 Antigen; C497902:MCAM protein, human; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human
keywords: CD146-positive cells; Extracellular matrix; Extracellular matrix-adherent cells; Plastic non-adherent cells; Pluripotent stem cells; Three germ layer tissue formation in vivo; Umbilical cord blood