Tendon graft revitalization using adult anterior cruciate ligament (ACL)-derived CD34+ cell sheets for ACL reconstruction

• Published in: Biomaterials Vol. 34; no. 22; pp. 5476 - 5487
• Main Authors: Mifune, Yutaka, Matsumoto, Tomoyuki, Takayama, Koji, Terada, Satoshi, Sekiya, Naosumi, Kuroda, Ryosuke, Kurosaka, Masahiro, Fu, Freddie H, Huard, Johnny
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.07.2013
• Subjects: Adult; Advanced Basic Science; Angiogenesis; Animals; Anterior Cruciate Ligament - cytology; Anterior Cruciate Ligament - physiopathology; Anterior Cruciate Ligament - transplantation; Anterior Cruciate Ligament Reconstruction; Antigens, CD34 - metabolism; Biomechanical Phenomena; Bone and Bones - pathology; Cell Culture Techniques - methods; Cell Movement; Cells, Cultured; Dentistry; Enzyme-Linked Immunosorbent Assay; Female; Fluorescent Antibody Technique; Humans; Ligament; Osteogenesis; Proprioception; Rats; Rats, Nude; Recovery of Function; Soft tissue biomechanics; Stem cell; Tendons - pathology; Tendons - physiopathology; Tendons - transplantation; Vascular Endothelial Growth Factor A - secretion; Wound Healing; Young Adult; Ligament; Angiogenesis; Soft tissue biomechanics; Stem cell; Osteogenesis
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2013.04.013

Abstract As a new strategy for enhancing recovery after anterior cruciate ligament (ACL) reconstruction, we developed a cell sheet wrapped graft using ACL-derived CD34+ cells. Our results from an ex vivo cell migration assay demonstrated gradual cell migration into the graft from the cell sheet, and an enzyme-linked immunosorbent assay indicated that the cell sheet cultures secreted a significantly greater amount of VEGF than typical monolayer cultures. In the in vivo study, the rats received one of three possible ACL reconstruction treatments; 1) a tendon graft wrapped in an ACL-derived CD34+ cell sheet, 2) a tendon graft and ACL-derived CD34+ cell injection, or 3) the control group that received just the tendon graft. The in vivo studies revealed that the ACL-derived CD34+ cell sheet wrapped grafts demonstrated a greater number of the cells derived from the cell sheets incorporated within the bone tunnel site and grafted tendon. We believe the incorporated CD34+ cells enhanced the healing of both the bone–tendon junction and the grafted tendon in the reconstructed rat ACLs by increasing proprioceptive recovery, graft maturation, and biomechanical strength. ACL-derived CD34+ cell sheet wrapped grafts could become a promising strategy to revitalize tendon autografts and recovery after ACL reconstruction resulting in superior and quicker recovery in patients requiring ACL reconstruction.