title: The homing of bone marrow MSCs to non-osseous sites for ectopic bone formation induced by osteoinductive calcium phosphate.
abstract: Osteoinductive biomaterials are promising for bone repair. There is no direct proof that bone marrow mesenchymal stem cells (BMSCs) home to non-osseous sites and participate in ectopic bone formation induced by osteoinductive bioceramics. The objective of this study was to use a sex-mismatched beagle dog model to investigate BMSC homing via blood circulation to participate in ectopic bone formation via osteoinductive biomaterial. BMSCs of male dogs were injected into female femoral marrow cavity. The survival and stable chimerism of donor BMSCs in recipients were confirmed with polymerase chain reaction (PCR) and fluorescence in situ hybridization (FISH). Biphasic calcium phosphate (BCP) granules were implanted in dorsal muscles of female dogs. Y chromosomes were detected in samples harvested from female dogs which had received male BMSCs. At 4 weeks, cells with Y-chromosomes were distributed in the new bone matrix throughout the BCP granule implant. At 6 weeks, cells with Y chromosomes were present in newly mineralized woven bone. TRAP positive osteoclast-like cells were observed in 4-week implants, and the number of such cells decreased from 4 to 6 weeks. These results show that osteoprogenitors were recruited from bone marrow and homed to ectopic site to serve as a cell source for calcium phosphate-induced bone formation. In conclusion, BMSCs were demonstrated to migrate from bone marrow through blood circulation to non-osseous bioceramic implant site to contribute to ectopic bone formation in a canine model. BCP induced new bone in muscles without growth factor delivery, showing excellent osteoinductivity that could be useful for bone tissue engineering.
authors.affiliation: State Key Laboratory of Oral Diseases, Sichuan University, Chengdu, China.
authors.forename: Guodong
authors.initials: G
authors.lastname: Song
authors.forename: Pamela
authors.initials: P
authors.lastname: Habibovic
authors.forename: Chongyun
authors.initials: C
authors.lastname: Bao
authors.forename: Jing
authors.initials: J
authors.lastname: Hu
authors.forename: Clemens A
authors.initials: CA
authors.lastname: van Blitterswijk
authors.forename: Huipin
authors.initials: H
authors.lastname: Yuan
authors.forename: Wenchuan
authors.initials: W
authors.lastname: Chen
authors.forename: Hockin H K
authors.initials: HH
authors.lastname: Xu
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D001854:Bone Marrow Cells / Q000166:cytology; D001842:Bone and Bones / Q000502:physiology*; D002130:Calcium Phosphates / Q000494:pharmacology*; D002465:Cell Movement; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D010010:Osteoclasts; D010012:Osteogenesis; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D014998:Y Chromosome
chemical_list: D001672:Biocompatible Materials; D002130:Calcium Phosphates