Local Transplantation of Granulocyte Colony Stimulating Factor‐Mobilized CD34+ Cells for Patients With Femoral and Tibial Nonunion: Pilot Clinical Trial

• Published in: Stem cells translational medicine 2014-01, Vol.3 (1), p.128-134
• Main Authors: Kuroda, Ryosuke, Matsumoto, Tomoyuki, Niikura, Takahiro, Kawakami, Yohei, Fukui, Tomoaki, Lee, Sang Yang, Mifune, Yutaka, Kawamata, Shin, Fukushima, Masanori, Asahara, Takayuki, Kawamoto, Atsuhiko, Kurosaka, Masahiro
• Format: Article
• Language: English
• Subjects: Adult; Antigens, CD34 - metabolism; Atelocollagen; Autografts; Blood; CD34 antigen; CD34+ cells; Clinical trial; Clinical trials; Colonies; Colony-stimulating factor; Cytokines; Data analysis; Drug dosages; FDA approval; Female; Femoral Fractures - diagnostic imaging; Femoral Fractures - therapy; Femur; Fracture Healing; Fractures; Fractures, Ununited - diagnostic imaging; Fractures, Ununited - therapy; G-CSF; Granulocyte Colony-Stimulating Factor - therapeutic use; Granulocytes; Growth factors; Hematopoietic Stem Cell Mobilization - methods; Humans; Ischemia; Leukocytes (granulocytic); Male; Middle Aged; Nonunion; Peripheral blood; Pilot Projects; Radiography; Stem Cell Transplantation - methods; Stem cells; Stem Cells - cytology; Stem Cells - metabolism; Studies; Tibial Fractures - diagnostic imaging; Tibial Fractures - therapy; Tissue Engineering and Regenerative Medicine; Transplantation; Treatment Outcome; Young Adult
• ISSN: 2157-6564; 2157-6580
• DOI: 10.5966/sctm.2013-0106

This paper reports a phase I/IIa clinical trial regarding transplantation of autologous, granulocyte colony stimulating factor‐mobilized CD34+ cells with atelocollagen scaffold for patients with femoral or tibial fracture nonunion. The results suggest feasibility, safety, and potential effectiveness of CD34+ cell therapy in patients with nonunion. Most bone fractures typically heal, although a significant proportion (5%–10%) of fractures fail to heal, resulting in delayed union or persistent nonunion. Some preclinical evidence shows the therapeutic potential of peripheral blood CD34+ cells, a hematopoietic/endothelial progenitor cell‐enriched population, for bone fracture healing; however, clinical outcome following transplantation of CD34+ cells in patients with fracture has never been reported. We report a phase I/IIa clinical trial regarding transplantation of autologous, granulocyte colony stimulating factor‐mobilized CD34+ cells with atelocollagen scaffold for patients with femoral or tibial fracture nonunion (n = 7). The primary endpoint of this study is radiological fracture healing (union) by evaluating anteroposterior and lateral views at week 12 following cell therapy. For the safety evaluation, incidence, severity, and outcome of all adverse events were recorded. Radiological fracture healing at week 12 was achieved in five of seven cases (71.4%), which was greater than the threshold (18.1%) predefined by the historical outcome of the standard of care. The interval between cell transplantation and union, the secondary endpoint, was 12.6 ± 5.4 weeks (range, 8–24 weeks) for clinical healing and 16.1 ± 10.2 weeks (range, 8–36 weeks) for radiological healing. Neither deaths nor life‐threatening adverse events were observed during the 1‐year follow‐up after the cell therapy. These results suggest feasibility, safety, and potential effectiveness of CD34+ cell therapy in patients with nonunion.