Human Amniotic Mesenchymal Stromal Cells Promote Bone Regeneration via Regulating Ameloblastoma-Derived-Bone Marrow Mesenchymal Cells Crosstalk and Autophagy in Ameloblastoma Microenvironment.

Abstract

Background: Growing evidence validates the vital function of mesenchymal stem cells (MSCs) in tumor development. Our previous findings have illustrated the role of MSCs in the invasion and recurrence of ameloblastoma. Stem cells can be transplanted to release paracrine factors in the tumor microenvironment (TME) to inhibit tumor progression and recurrence. The paracrine function of human amniotic mesenchymal stromal cells (HAMSCs) benefits bone regeneration. However, the dual function of HAMSCs in inhibiting tumor progression and promoting bone regeneration in the TME remains unknown.

Methods: To analyze the role of HAMSCS in the cross-talk between mesenchymal ameloblastoma-derived cells (M-AMCs), human bone marrow mesenchymal stem cells (HBMSCs), and HAMSCs, an in vitro co-culture system of M-AMCs, HBMSCS, and HAMSCS was prepared. An in vivo ectopic transplantation model was employed further to detect the therapeutic effect of HAMSCs on bone regeneration.

Results: A high-level basal autophagy was detected in the stroma of ameloblastoma. In the in vitro co-culture models, M-AMCs suppressed the proliferation, differentiation, migration, and autophagy of HBMSCs, and conversely, HBMSCs promoted the above phenotypes of M-AMCs. HAMSCs promoted the proliferation, differentiation, migration and autophagy of the co-cultured HBMSCs. Additionally, HAMSCs mediated the cross-talk between M-AMCs and HBMSCs. The in vivo ectopic transplantation model indicated that transplanted HAMSCs promoted bone regeneration by inhibiting the growth of M-AMCs and enhancing autophagy, as well as osteogenesis in bone defects of mice.

Conclusions: The interaction of M-AMCs and HBMSCs may be associated with ameloblastoma recurrence. HAMSCs regulate the cross-talk between M-AMCs and HBMSCs to increase the autophagic level in the TME, thus inhibiting the progression and recurrence of ameloblastoma and promoting bone regeneration. Therefore, HAMSC-based therapy provides an alternative to facilitate bone regeneration and repair of ameloblastoma-induced bone defects.