title: Therapeutic potential of vasculogenesis and osteogenesis promoted by peripheral blood CD34-positive cells for functional bone healing.
abstract: Failures in fracture healing are mainly caused by a lack of vascularization. Adult human circulating CD34+ cells, an endothelial/hematopoietic progenitor-enriched cell population, have been reported to differentiate into osteoblasts in vitro; however, the therapeutic potential of CD34+ cells for fracture healing is still unclear. Therefore, we performed a series of experiments to test our hypothesis that functional fracture healing is supported by vasculogenesis and osteogenesis via regenerative plasticity of CD34+ cells. Peripheral blood CD34+ cells, isolated from total mononuclear cells of adult human volunteers, showed gene expression of osteocalcin in 4 of 20 freshly isolated cells by single cell reverse transcriptase-polymerase chain reaction analysis. Phosphate-buffered saline, mononuclear cells, or CD34+ cells were intravenously transplanted after producing nonhealing femoral fractures in nude rats. Reverse transcriptase-polymerase chain reaction and immunohistochemical staining at the peri-fracture site demonstrated molecular and histological expression of human-specific markers for endothelial cells and osteoblasts at week 2. Functional bone healing assessed by biomechanical as well as radiological and histological examinations was significantly enhanced by CD34+ cell transplantation compared with the other groups. Our data suggest circulating human CD34+ cells have therapeutic potential to promote an environment conducive to neovascularization and osteogenesis in damaged skeletal tissue, allowing the complete healing of fractures.
authors.affiliation: Stem Cell Translational Research, Kobe Institute of Biomedical Research and Innovation/Riken Center for Developmental Biology, 2-2 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Atsuhiko
authors.initials: A
authors.lastname: Kawamoto
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Kuroda
authors.forename: Masakazu
authors.initials: M
authors.lastname: Ishikawa
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Mifune
authors.forename: Hiroto
authors.initials: H
authors.lastname: Iwasaki
authors.forename: Masahiko
authors.initials: M
authors.lastname: Miwa
authors.forename: Miki
authors.initials: M
authors.lastname: Horii
authors.forename: Saeko
authors.initials: S
authors.lastname: Hayashi
authors.forename: Akira
authors.initials: A
authors.lastname: Oyamada
authors.forename: Hiromi
authors.initials: H
authors.lastname: Nishimura
authors.forename: Satoshi
authors.initials: S
authors.lastname: Murasawa
authors.forename: Minoru
authors.initials: M
authors.lastname: Doita
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kurosaka
authors.forename: Takayuki
authors.initials: T
authors.lastname: Asahara
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D018952:Antigens, CD34 / Q000032:analysis*; D002465:Cell Movement; D002478:Cells, Cultured; D042783:Endothelial Cells; D005260:Female; D005264:Femoral Fractures / Q000473:pathology / Q000628:therapy*; D005269:Femur / Q000098:blood supply* / Q000473:pathology; D015870:Gene Expression; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000737:chemistry / Q000637:transplantation*; D051379:Mice; D018919:Neovascularization, Physiologic / Q000187:drug effects; D015675:Osteocalcin / Q000235:genetics; D010012:Osteogenesis / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011923:Rats, Nude
chemical_list: D020533:Angiogenesis Inhibitors; D018952:Antigens, CD34; D012333:RNA, Messenger; D015675:Osteocalcin