Scripties UMCG - Rijksuniversiteit Groningen
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Healing of Segmental Femoral Defect with Endothelial ProgenitorCells (EPCs) in Rats: A Dose- Response Study

(2018) Hegner, C. (Christian)

Introduction: Fracture nonunion remains a major challenge for orthopaedic surgeons and has a
devastating impact on patients’ quality of life. Endothelial progenitor cells (EPCs) are a
heterogeneous cell population with osteogenic and angiogenic properties, which have shown
their potential for bone healing in multiple animal studies. However, the optimal dose of EPCs
in bone healing is unknown. Therefore, the purpose of this study was to investigate and compare
the effectiveness of five different doses of EPCs (0.1, 0.5, 1, 2 and 4x106) in a rat nonunion
Methods: 5-mm segmental femoral bone defects were surgically created in Fischer-344 rats and
fixed with a mini-plate. The defects were randomly filled with a cell-free gelatin scaffold
(control group), or with 0.1, 0.5, 1, 2 or 4x106 EPCs. Implanted EPCs were isolated from bone
marrow of donor rats and cultured in endothelial growth medium for 7-8 days prior to surgery.
Bone healing was assessed by radiography, micro-CT and biomechanical testing.
Results: Radiographic bone healing was significantly improved in the 0.5, 1, 2 and 4x106 EPCs
groups compared to the control group. Quantitative analyses by micro-CT revealed that 0.5, 1
and 2x106 EPCs resulted in the greatest volume of newly formed bone. 2x106 EPCs were the
only group capable of significantly increasing all biomechanical properties, demonstrating the
best functional regeneration.
Conclusion: Our results suggest that 2x106 EPCs is the optimal dose. Additionally, our study
highlights the current lack and the importance of dose-response studies in developing effective
cell therapies.

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