Theranostics 2020; 10(14):6216-6230. doi:10.7150/thno.45249

Research Paper

Human amniotic mesenchymal stromal cells promote bone regeneration via activating endogenous regeneration

Fei Jiang1,2,3,*✉, Wenjie Zhang3,*, Mingliang Zhou3, Zhixuan Zhou1,2, Ming Shen1,2, Ning Chen1, Xinquan Jiang3,✉

1. Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, No. 140, Han Zhong Road, Nanjing 210029, China
2. Department of General Dentistry, Affiliated Hospital of Stomatology, Nanjing Medical University, No. 136, Han Zhong Road, Nanjing 210029, China
3. Department of Prosthodontics; Shanghai Engineering Research Center of Advanced Dental Technology and Materials; Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, No. 639 Zhizaoju Road, Shanghai 200011, China
* These authors contributed equally.

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Citation:
Jiang F, Zhang W, Zhou M, Zhou Z, Shen M, Chen N, Jiang X. Human amniotic mesenchymal stromal cells promote bone regeneration via activating endogenous regeneration. Theranostics 2020; 10(14):6216-6230. doi:10.7150/thno.45249. Available from https://www.thno.org/v10p6216.htm

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Abstract

Rationale: The effectiveness of stem cell based-therapy for bone regeneration has been demonstrated; yet, clinical application of autologous stem cells is still limited by invasive acquisition, long culture processes, and high cost. Besides, it remains controversial whether autologous stem cells could directly participate in tissue repair after differentiation. Thus, increasing allogeneic stem cells have been developed into drugs to indirectly activate endogenous regeneration and induce tissue regeneration. Human amniotic mesenchymal stromal cells (HAMSCs) have been extensively studied, showing multiple regulatory functions, but mechanisms of HAMSCs in promoting bone regeneration are remain unclear.

Methods: Proteome profile of HAMSCs and their functions on vascularized bone regeneration were investigated in vitro, while rabbit cranial defect model was used to further detect the effects of bone formation in vivo.

Results: HAMSCs secrete many osteogenic, angiogenic, and immunomodulatory cytokines. In vitro, HAMSCs can promote human bone-marrow mesenchymal stromal cells (HBMSCs) migration and osteogenic differentiation; promote the capillary-tube formation of human umbilical vascular endothelial cells (HUVECs), induce HUVECs migration and pro-angiogenic genes expression, and promote M2 macrophage polarization. Further, in vivo studies suggested that transplanted HAMSCs could survive and induce M2 macrophages to secrete bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF) in rabbits' skull defects at an early stage, and, in turn, promote more new bone formation.

Conclusion: HAMSCs have good biocompatibility and paracrine function to promote bone repair by stimulating endogenous regeneration.

Keywords: HAMSCs, paracrine function, M2 macrophage polarization, endogenous regeneration, vascularized bone regeneration