Jäger Marcus, Degistirici Ozer, Knipper Andreas, Fischer Johannes, Sager Martin, Krauspe Rüdiger
Research Laboratory for Regenerative Medicine and Biomaterials, Department of Orthopaedics, Heinrich-Heine University Medical School, Duesseldorf, Germany.
J Bone Miner Res. 2007 Aug;22(8):1224-33. doi: 10.1359/jbmr.070414.
UNLABELLED: 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 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.
未标注：基于干细胞和组织工程的疗法已成为未来治愈骨缺损的一种有前景的选择。将人脐带血来源的间充质干细胞接种到胶原/磷酸三钙支架上，并异种移植到46只裸鼠的临界尺寸股骨缺损处。我们发现移植后4周内支架内及周围骨/骨髓中有人类细胞存活，且与无干细胞的对照组相比，骨愈合率有所提高。本研究支持脐带血干细胞在骨再生中的应用。 引言：临界尺寸骨缺损的治疗仍是骨科领域一个具有挑战性的问题。在本研究中，将脐带血来源的干细胞异种移植到无胸腺裸鼠的临界尺寸股骨缺损处后，对其存活、迁移及促进骨愈合的能力进行了阐明。 材料与方法：从人脐带血中分离出的无限制体细胞干细胞（USSCs）进行体外间充质潜能测试，并培养在I/III型胶原和β-磷酸三钙（β-TCP）支架上。将生物材料-USSC复合物移植到40只裸鼠的4毫米股骨缺损处，并用外固定器固定。12只未植入USSCs的动物作为对照。通过血液样本、X射线以及对不同器官进行组织学和免疫细胞化学分析，在术后最长10周的随访期内评估细胞存活、迁移和骨形成情况。 结果：52只裸鼠中，46只动物接受了评估（失访率：11.5%）。异种移植后4周内，人源干细胞在支架及相邻股骨内实现了植入。随着时间推移，人类细胞被宿主机体破坏。与对照组相比，我们发现研究组的骨形成有显著增加。USSC移植对无胸腺裸鼠的血细胞计数或体重无显著影响。虽然I/III型胶原支架在移植后10周几乎被吸收，但此时移植部位仍有大量TCP存在。 结论：人脐带血来源的干细胞在骨髓中显示出显著植入，在胶原-TCP支架内存活长达4周，并增加了裸鼠股骨缺损处的局部骨形成。
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