title: Superior Potential of CD34-Positive Cells Compared to Total Mononuclear Cells for Healing of Nonunion Following Bone Fracture.
abstract: We recently demonstrated that the local transplantation of human peripheral blood (PB) CD34(+) cells, an endothelial/hematopoietic progenitor cell-rich population, contributes to fracture repair via vasculogenesis/angiogenesis and osteogenesis. Human PB mononuclear cells (MNCs) are also considered a potential cell fraction for neovascularization. We have previously shown the feasibility of human PB MNCs to enhance fracture healing. However, there is no report directly comparing the efficacy for fracture repair between CD34(+) cells and MNCs. In addition, an unhealing fracture model, which does not accurately resemble a clinical setting, was used in our previous studies. To overcome these issues, we compared the capacity of human granulocyte colony-stimulating factor-mobilized PB (GM-PB) CD34(+) cells and human GM-PB MNCs in a nonunion model, which more closely resembles a clinical setting. First, the effect of local transplantation of 1 × 10(5) GM-PB CD34(+) cells (CD34(+) group), 1 × 10(7) GM-PB MNCs (containing approximately 1 × 10(5) GM-PB CD34(+) cells) (MNC group), and phosphate-buffered saline (PBS) (PBS group) on nonunion healing was compared. Similar augmentation of blood flow recovery at perinonunion sites was observed in the CD34(+) and MNC groups. Meanwhile, a superior effect on nonunion repair was revealed by radiological, histological, and functional assessment in the CD34(+) group compared with the other groups. Moreover, through in vivo and in vitro experiments, excessive inflammation induced by GM-PB MNCs was confirmed and believed to be one of the mechanisms underlying this potency difference. These results strongly suggest that local transplantation of GM-PB CD34(+) cells is a practical and effective strategy for treatment of nonunion after fracture.
authors.affiliation: Group of Vascular Regeneration Research, Institute of Biomedical Research and Innovation, Kobe, Hyogo, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Fukui
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Mifune
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Taro
authors.initials: T
authors.lastname: Shoji
authors.forename: Yohei
authors.initials: Y
authors.lastname: Kawakami
authors.forename: Atsuhiko
authors.initials: A
authors.lastname: Kawamoto
authors.forename: Masaaki
authors.initials: M
authors.lastname: Ii
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Akimaru
authors.forename: Tomoya
authors.initials: T
authors.lastname: Kuroda
authors.forename: Miki
authors.initials: M
authors.lastname: Horii
authors.forename: Ayumi
authors.initials: A
authors.lastname: Yokoyama
authors.forename: Cantas
authors.initials: C
authors.lastname: Alev
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Kuroda
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kurosaka
authors.forename: Takayuki
authors.initials: T
authors.lastname: Asahara
mesh_terms: D018952:Antigens, CD34 / Q000378:metabolism*; D002454:Cell Differentiation; D050723:Fractures, Bone; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D019172:Transplantation Conditioning / Q000379:methods*; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D018952:Antigens, CD34