Local Transplantation of Ex Vivo Expanded Bone Marrow-Derived CD34-Positive Cells Accelerates Fracture Healing

Cell Transplantation

Article

Ryosuke Kuroda¹  Masahiro Kurosaka¹  Masaaki Ii²  Haruchika Masuda³  Atsuhiko Kawamoto⁴  Miki Horii⁴  Hiroshi Akimaru⁴  Ayumi Yokoyama⁴  Taro Shoji⁵  Tomoyuki Matsumoto⁵  Tomoya Kuroda⁵  Yutaka Mifune⁵  Yohei Kawakami⁵  Tomoaki Fukui⁵  Takayuki Asahara⁶  Cantas Alev⁷ 

[1] Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan;Department of Pharmacology, Osaka Medical College, Takatsuki, Osaka, Japan;Department of Regenerative Medicine Science, Tokai University School of Medicine, Isehara, Kanagawa, Japan;Group of Vascular Regeneration, Institute of Biomedical Research and Innovation, Kobe, Hyogo, Japan;Group of Vascular Regeneration, Institute of Biomedical Research and Innovation, Kobe, Hyogo, Japan;Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan;Group of Vascular Regeneration, Institute of Biomedical Research and Innovation, Kobe, Hyogo, Japan;Department of Regenerative Medicine Science, Tokai University School of Medicine, Isehara, Kanagawa, Japan;Group of Vascular Regeneration, Institute of Biomedical Research and Innovation, Kobe, Hyogo, Japan;Laboratory for Early Embryogenesis, RIKEN Center for Developmental Biology, Kobe, Hyogo, Japan;

关键词: Fracture healing;    Osteogenesis;    Angiogenesis;    Stem/progenitor cell;    Expansion;   

DOI  :  10.3727/096368912X654920

 received in 2011-09-12, accepted in 2012-02-25,  发布年份 2012

来源: Sage Journals

【 摘 要 】

Transplantation of bone marrow (BM) CD34+ cells, an endothelial/hematopoietic progenitor-enriched cell population, has shown therapeutic efficiency in the treatment of ischemic diseases enhancing neovascularization. However, the number of CD34+ cells obtained from bone marrow is not sufficient for routine clinical application. To overcome this issue, we developed a more efficient and clinically applicable CD34+ cell expansion method. Seven-day ex vivo expansion culture of BM CD34+ cells with a cocktail of five growth factors containing VEGF, SCF, IL-6, Flt-3 ligand, and TPO resulted in reproducible more than 20-fold increase in cell number. The favorable effect of the local transplantation of culture expanded (cEx)-BM CD34+ cells on rat unhealing fractures was equivalent or higher than that of nonexpanded (fresh) BM CD34+ cells exhibiting sufficient therapeutic outcome with frequent vasculogenic/osteogenic differentiation of transplanted cEx-BM CD34+ cells and fresh BM CD34+ cells as well as intrinsic enhancement of angiogenesis/osteogenesis at the treated fracture sites. Specifically, cEx-BM CD34+ cell treatment demonstrated the best blood flow recovery at fracture sites compared with the nonexpanded BM CD34+ cells. In vitro, cEx-BM CD34+ cells showed higher colony/tube-forming capacity than nonexpanded BM CD34+ cells. Both cells demonstrated differentiation potential into osteoblasts. Since fresh BM CD34+ cells can be easily collected from fracture sites at the time of primary operation and stored for future use, autologous cEx-BM CD34+ cell transplantation would be not only a simple but also a promising therapeutic strategy for unhealing fractures in the field of orthopedic trauma surgery.

【 授权许可】

Unknown   
© 2012 Cognizant Comm. Corp.

【 图 表 】

Figure 2

Figure 5.

Figure 3.

Figure 11.

Figure 2.

Figure 6.

Figure 9.