Administrations of peripheral blood CD34-positive cells contribute to medial collateral ligament healing via vasculogenesis.
Neoangiogenesis is a key process in the initial phase of ligament healing. Adult human circulating CD34+ cells, an endothelial/hematopoietic progenitor-enriched cell population, have been reported to contribute to neoangiogenesis; however, the therapeutic potential of CD34+ cells for ligament healing is still unclear. Therefore, we performed a series of experiments to test our hypothesis that ligament healing is supported by CD34+ cells via vasculogenesis. Granulocyte colony-stimulating factor-mobilized peripheral blood (GM-PB) CD34+ cells with atelocollagen (CD34+ group), GM-PB mononuclear cells (MNCs) with atelocollagen (MNC group), or atelocollagen alone (control group) was locally transplanted after the creation of medial collateral ligament injury in immunodeficient rats. Reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemical staining at the injury site demonstrated that molecular and histological expression of human-specific markers for endothelial cells was higher in the CD34+ group compared with the other groups at week 1. Endogenous effect, assessed by capillary density and mRNA expression of vascular endothelial growth factor, was significantly higher in CD34+ cell group than the other groups. In addition to the observation that, as assessed by real-time RT-PCR, gene expression of ligament-specific marker was significantly higher in the CD34+ group than in the other groups, ligament healing assessed by macroscopic, histological, and biomechanical examination was significantly enhanced by CD34+ cell transplantation compared with the other groups. Our data strongly suggest that local transplantation of circulating human CD34+ cells may augment the ligament healing process by promoting a favorable environment through neovascularization.
Tei
Katsumasa
K
Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine 7-5-1, Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
Matsumoto
Tomoyuki
T
Mifune
Yutaka
Y
Ishida
Kazunari
K
Sasaki
Ken
K
Shoji
Taro
T
Kubo
Seiji
S
Kawamoto
Atsuhiko
A
Asahara
Takayuki
T
Kurosaka
Masahiro
M
Kuroda
Ryosuke
R
D000328:Adult; D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D064987:Cell- and Tissue-Based Therapy; D017885:Collateral Ligaments / Q000187:drug effects / Q000473:pathology*; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D007249:Inflammation; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010641:Phenotype; D051381:Rats; D011923:Rats, Nude; D014945:Wound Healing / Q000187:drug effects
D020533:Angiogenesis Inhibitors; D018952:Antigens, CD34; D016179:Granulocyte Colony-Stimulating Factor