Recruitment of a Host's Osteoprogenitor Cells Using Exogenous Mesenchymal Stem Cells Seeded on Porous Ceramic

Abstract

The contribution of the host's circulating progenitor cells after implantation of mesenchymal stem cells (MSC)/bioscaffold combinations for repairing bone defects has not been elucidated, although this issue affects the clinical application of the tissue engineering approach. We implanted blocks of hydroxyapatite loaded with murine MSCs into syngenic, allogenic, and immunocompromised recipients. After 8 weeks, we found that bone tissue was formed in syngenic and immunocompromised animals. The implanted cells appeared pivotal in the early stages of tissue development, but cells of the recipient's origin finally made bone. In this system, osteoprogenitors migrated from the recipient to the implant, whereas the implanted cells left the scaffold and entered the circulatory flow. We observed rapid destruction of implanted cells when allogenic MSC/bioscaffold combinations were grafted onto immunocompetent recipients without immunosuppressant therapy. This destruction blocked the recruitment process and did not allow the formation of new bone tissue. The possibility that the implanted exogenous MSCs could engage the host's osteoprogenitor cells to form new bone tissue could open new perspectives for the tissue engineering approach to bone repair, including the opportunity of using allogenic cells combined with a temporary immunosuppressant therapy, stimulating the replacement of the exogenous cells with autologous cells.

Titanium-Enriched Hydroxyapatite–Gelatin Scaffolds with Osteogenically Differentiated Progenitor Cell Aggregates for Calvaria Bone Regeneration

“…48,49 The immune rejection mechanism can start between day 3 and day 8 after implantation of allogeneic stem cells. 45 In our previous studies, we found no rejection-associated tissue necrosis or mixed lymphocytic reaction 10 days after implantation of OD-MAPCs. 5 In fact, OD-MAPCs were found growing in HAP porous areas between day 4 and 10 in calvaria defects.…”

“…45 In addition, allogeneic adult stem cells can be defect-retained for more than 9 weeks following implantation, 46 although these findings are species dependent. 45 Species-specific differences do exist in the regulation of the immunity, in the mechanism of bone formation, or in the site of implantation. In recent literature, higher ratios of M2/M1 macrophages concomitantly with an absence of a foreign body response have been found with scaffolds having 30-40-mm pores when compared to hosts with nonporous implants.…”

In Vivo Implanted Bone Marrow-Derived Mesenchymal Stem Cells Trigger a Cascade of Cellular Events Leading to the Formation of an Ectopic Bone Regenerative Niche

“…one marrow stromal cells (BMSCs), also known as BM-derived mesenchymal stem cells (MSCs), are considered effective therapeutic agents in a variety of clinical situations promoting the repair of injured tissues [1] not only for their multipotent differentiation potential, but also for their interesting role as cellular modulators [2][3][4][5]. However, it's still unknown why, in some cases, transplanted MSCs directly contribute to form a new tissue, whereas in others they activate endogenous mechanisms leading to new tissue formation by the host cells.…”

Orthopaedic Research in Italy: State of the Art

“…One ofthe crucial aspects ofbone engineering is the prediction of the bone healing capacity of the produced constructs and if the osteogenesis induced by tissue engineering is similar to the physiological bone formation. Some recent researches created models for the study of these aspects (90,91,92).…”