Bone Healing and Migration of Cord Blood—Derived Stem Cells Into a Critical Size Femoral Defect After Xenotransplantation

Authors

  • Marcus Jäger MD, PhD,

    Corresponding author
    1. Research Laboratory for Regenerative Medicine and Biomaterials, Department of Orthopaedics, Heinrich-Heine University Medical School, Duesseldorf, Germany
    2. Department of Orthopedic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
    • Research Laboratory for Regenerative Medicine and Biomaterials, Department of Orthopaedics, Heinrich-Heine University Medical School, Moorenstr. 5, D-40225 Duesseldorf, Germany
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  • Özer Degistirici,

    1. Kourion Therapeutics AG, Langenfeld, Germany
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  • Andreas Knipper,

    1. Kourion Therapeutics AG, Langenfeld, Germany
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  • Johannes Fischer,

    1. Institute of Transplantation Diagnostic and Cell Therapy, Heinrich-Heine-University, Duesseldorf, Germany
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  • Martin Sager,

    1. Animal Research Laboratory, Heinrich-Heine-University, Duesseldorf, Germany
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  • Rüdiger Krauspe

    1. Research Laboratory for Regenerative Medicine and Biomaterials, Department of Orthopaedics, Heinrich-Heine University Medical School, Duesseldorf, Germany
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  • The authors state that they have no conflicts of interest.

Abstract

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.

Introduction: 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.

Materials and 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 β-tricalcium phosphate (β-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.

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