Bone healing and migration of cord blood-derived stem cells into a critical size femoral defect after xenotransplantation.
Stem cell and tissue engineering-based therapies have become a promising option to heal bony defects in the future. Human cord blood-derived mesenchymal stem cells were seeded onto a collagen/tricalcium phosphate scaffold and xenotransplanted into critical size femoral defects of 46 nude rats. We found a survival of human cells within the scaffold and surrounding bone/bone marrow up to 4 wk after transplantation and an increased bone healing rate compared with controls without stem cells. This study supports the application of cord blood stem cells for bone regeneration.


BACKGROUND
The treatment of critical size bone defects is still a challenging problem in orthopedics. In this study, the survival, migration, and bone healing promoting potency of cord blood-derived stem cells were elucidated after xenotransplantation into a critical size femoral defect in athymic nude rats.


METHODS
Unrestricted somatic stem cells (USSCs) isolated from human cord blood were tested toward their mesenchymal in vitro potency and cultivated onto a collagen I/III and beta-tricalcium phosphate (beta-TCP) scaffold. The biomaterial-USSC composite was transplanted into a 4-mm femoral defect of 40 nude rats and stabilized by an external fixator. Twelve animals without USSCs served as controls. Cell survival, migration, and bone formation were evaluated by blood samples, X-rays, and histological and immunocytochemical analysis of different organs within a maximal postoperative follow-up of 10 wk.


RESULTS
Of the 52 nude rats, 46 animals were evaluated (drop-out rate: 11.5%). Human-derived stem cells showed an engraftment within the scaffold and adjacent femur up to 4 wk after xenotransplantation. With further time, the human cells were destroyed by the host organism. We found a significant increase in bone formation in the study group compared with controls. USSC transplantation did not significantly influence blood count or body weight in athymic nude rats. Whereas the collagen I/III scaffold was almost resorbed 10 wk after transplantation, there were still significant amounts of TCP present in transplantation sites at this time.


CONCLUSIONS
Human cord blood-derived stem cells showed significant engraftment in bone marrow, survived within a collagen-TCP scaffold up to 4 wk, and increased local bone formation in a nude rat's femoral defect.
Jäger
Marcus
M
Research Laboratory for Regenerative Medicine and Biomaterials, Department of Orthopaedics, Heinrich-Heine University Medical School, Duesseldorf, Germany. Jaeger@med.uni-duesseldorf.de
Degistirici
Ozer
O
Knipper
Andreas
A
Fischer
Johannes
J
Sager
Martin
M
Krauspe
Rüdiger
R
D000818:Animals; D001772:Blood Cell Count; D001835:Body Weight; D002465:Cell Movement; D002470:Cell Survival; D002478:Cells, Cultured; D005269:Femur / Q000473:pathology* / Q000601:surgery; D053686:Fetal Stem Cells / Q000166:cytology* / Q000637:transplantation*; D017102:Fracture Healing; D050723:Fractures, Bone / Q000473:pathology* / Q000601:surgery; D006801:Humans; D007700:Kinetics; D051381:Rats; D011923:Rats, Nude; D014183:Transplantation, Heterologous