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 (Ca(2+)) and phosphate (P(i)) 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 Ca(2+) and P(i) 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.
authors.affiliation: Laboratory for Skeletal Development and Joint Disorders, Katholieke Universiteit Leuven, O&N 1, Herestraat 49, Bus 813, 3000 Leuven, Belgium. yokechin.chai@med.kuleuven.be
authors.forename: Yoke Chin
authors.initials: YC
authors.lastname: Chai
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Roberts
authors.forename: Eline
authors.initials: E
authors.lastname: Desmet
authors.forename: Greet
authors.initials: G
authors.lastname: Kerckhofs
authors.forename: Nick
authors.initials: N
authors.lastname: van Gastel
authors.forename: Liesbet
authors.initials: L
authors.lastname: Geris
authors.forename: Geert
authors.initials: G
authors.lastname: Carmeliet
authors.forename: Jan
authors.initials: J
authors.lastname: Schrooten
authors.forename: Frank P
authors.initials: FP
authors.lastname: Luyten
mesh_terms: D000293:Adolescent; D001672:Biocompatible Materials / Q000138:chemical synthesis; D001846:Bone Development / Q000502:physiology*; D002130:Calcium Phosphates / Q000737:chemistry*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D008297:Male; D008422:Materials Testing; D010006:Osteoblasts / Q000166:cytology* / Q000502:physiology; D010012:Osteogenesis / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D001672:Biocompatible Materials; D002130:Calcium Phosphates; C020243:calcium phosphate