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Erschienen in: International Orthopaedics 11/2017

24.08.2017 | Original Paper

Subtypes of endothelial progenitor cells affect healing of segmental bone defects differently

verfasst von: Erica M. Giles, Charles Godbout, Wendy Chi, Michael A. Glick, Tony Lin, Ru Li, Emil H. Schemitsch, Aaron Nauth

Erschienen in: International Orthopaedics | Ausgabe 11/2017

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Abstract

Purpose

Treating fracture nonunion with endothelial progenitor cells (EPCs) is a promising approach. Nevertheless, the effect of different EPC-related cell populations remains unclear. In this study, we compared the therapeutic potential of early (E-EPCs) and late EPCs (L-EPCs).

Methods

Male Fischer 344 rats were used for cell isolation and in vivo experiments. Bone marrow-derived E-EPCs and L-EPCs were kept in culture for seven to ten days and four weeks, respectively. For each treatment group, we seeded one million cells on a gelatin scaffold before implantation in a segmental defect created in a rat femur; control animals received a cell-free scaffold. Bone healing was monitored via radiographs for up to ten weeks after surgery. In vitro, secretion of vascular endothelial growth factor (VEGF) and bone morphogenetic protein (BMP)-2 was quantified by ELISA for both cell populations. Tube formation assays were also performed.

Results

Final radiographs showed complete (four out of five rats) or partial (one out of five rats) union with E-EPC treatment. In contrast, complete healing was achieved in only one of five animals after L-EPC implantation, while control treatment resulted in nonunion in all animals. In vitro, E-EPCs released more VEGF, but less BMP-2 than L-EPCs. In addition, L-EPCs formed longer and more mature tubules on basement membrane matrix than E-EPCs. However, co-culture with primary osteoblasts stimulated tubulogenesis of E-EPCs while inhibiting that of L-EPCs.

Conclusions

We demonstrated that bone marrow-derived E-EPCs are a better alternative than L-EPCs for treatment of nonunion. We hypothesize that the expression profile of E-EPCs and their adaptation to the local environment contribute to superior bone healing.
Literatur
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Metadaten
Titel
Subtypes of endothelial progenitor cells affect healing of segmental bone defects differently
verfasst von
Erica M. Giles
Charles Godbout
Wendy Chi
Michael A. Glick
Tony Lin
Ru Li
Emil H. Schemitsch
Aaron Nauth
Publikationsdatum
24.08.2017
Verlag
Springer Berlin Heidelberg
Erschienen in
International Orthopaedics / Ausgabe 11/2017
Print ISSN: 0341-2695
Elektronische ISSN: 1432-5195
DOI
https://doi.org/10.1007/s00264-017-3613-0

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