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Mechanisms of ectopic bone formation by human osteoprogenitor cells on CaP biomaterial carriers

Paper ID Volume ID Publish Year Pages File Format Full-Text
6961 526 2012 16 PDF Available
Title
Mechanisms of ectopic bone formation by human osteoprogenitor cells on CaP biomaterial carriers
Abstract

Stem cell-based strategies for bone regeneration, which use calcium phosphate (CaP)-based biomaterials in combination with developmentally relevant progenitor populations, have significant potential for clinical repair of skeletal defects. However, the exact mechanism of action and the stem cell–host-material interactions are still poorly understood. We studied if pre-conditioning of human periosteum-derived cells (hPDCs) in vitro could enhance, in combination with a CaP-based biomaterial carrier, ectopic bone formation in vivo. By culturing hPDCs in a biomimetic calcium (Ca2+) and phosphate (Pi) enriched culture conditions, we observed an enhanced cell proliferation, decreased expression of mesenchymal stem cell (MSC) markers and upregulation of osteogenic genes including osterix, Runx2, osteocalcin, osteopontin, and BMP-2. However, the in vitro pre-conditioning protocols were non-predictive for in vivo ectopic bone formation. Surprisingly, culturing in the presence of Ca2+ and Pi supplements resulted in partial or complete abrogation of in vivo ectopic bone formation. Through histological, immunohistochemical and microfocus X-ray computed tomography (μCT) analysis of the explants, we found that in situ proliferation, collagen matrix deposition and the mediation of osteoclastic activity by hPDCs are associated to their ectopic bone forming capacity. These data were validated by the multivariate analysis and partial least square regression modelling confirming the non-predictability of in vitro parameters on in vivo ectopic bone formation. Our series of experiments provided further insights on the stem cell–host-material interactions that govern in vivo ectopic bone induction driven by hPDCs on CaP-based biomaterials.

Keywords
Ectopic bone formation; Calcium phosphate; Stem cell–host-material interaction; Mesenchymal stem cells; Osteogenic differentiation
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Mechanisms of ectopic bone formation by human osteoprogenitor cells on CaP biomaterial carriers
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 33, Issue 11, April 2012, Pages 3127–3142
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us