The recruitment of two consecutive and different waves of host stem/progenitor cells during the development of tissue-engineered bone in a murine model.
Angiogenesis plays a central role in bone regeneration, not only for the transport of nutrients, but also for locally directing skeletal stem/progenitor cells. Following ectopic implantation of porous ceramic cubes seeded with mouse GFP-labeled mesenchymal stem cells (MSC) into syngenic mice, we investigated the cascade of events leading to bone formation. Implants harvested at different times were enzymatically digested to generate single-cell suspensions. Recovered cells were sorted to separate GFP+implanted MSC and host recruited GFP- cells. We isolated and characterized two different waves of cells, migrating from the host to the MSC-seeded ceramic. The first migrated cell population, recovered 7 days after implantation, was enriched in CD31+endothelial progenitors, while the second one, recruited at day 11, was enriched in CD146+pericyte-like cells. Both populations were not recruited into the scaffold following implantation of a non-MSC seeded ceramic. Pericyte-like cell mobilization was dependent on the first migrated endothelial cell population. Pericyte-like cells retained properties distinctive of stem cells, such as capacity of performing a high number of in vitro cell divisions and showed an osteogenic potential. Studies on the cross talk between implanted exogenous MSC and resident stem/progenitor cells could open new perspectives for future clinical applications.
Tasso
Roberta
R
Department of Oncology, Biology, and Genetics, University of Genova, Largo Rosanna Benzi 10, 16132 Genova, Italy.
Fais
Franco
F
Reverberi
Daniele
D
Tortelli
Federico
F
Cancedda
Ranieri
R
D000818:Animals; D001842:Bone and Bones / Q000166:cytology / Q000502:physiology*; D002460:Cell Line; D002465:Cell Movement; D049109:Cell Proliferation; D002516:Ceramics; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008822:Mice, Transgenic; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D023822:Tissue Engineering