화학공학소재연구정보센터
홈 로그인 로그아웃 연락처 사이트맵
Journal of Industrial and Engineering Chemistry, Vol.107, 493-504, March, 2022
DOI10.1016/j.jiec.2021.12.019  Export Citation
Multiple stimulation with spheroids comprising salivary gland and adipose-derived stem cells enhances regeneration of radiation-damaged salivary glands
Jooyoung Kim1, Min Rye Eom1, Eun Ji Jeong1, Ji Suk Choi1, and Seong Keun Kwon1, 2, †
  • 1Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University Hospital, Seoul 03080, Republic of Korea
  • 2Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University College of Medicine, Seoul 03080, Republic of Korea
E-mail:
Tissue engineering approaches using a single stem cell type have been unsuccessful in achieving regeneration of radiation-damaged salivary glands (SGs). Therefore, we combined adult SG stem cells (SGSCs) and adipose-derived stem cells (ASCs) in optimized spheroids to enhance the regeneration of damaged SGs in mice. SGSC/ASC spheroids survived longer and secreted more vascular endothelial growth factor (VEGF) than did SGSC spheroids. To enhance cell viability and differentiation, SGSC/ASC spheroids were stimulated with the Wnt/β-catenin signaling activator CHIR99021 and retinoic acid inhibitor BMS431 to maintain stemness. FGF7/10 induced the differentiation of multiple stimulated SGSC/ASC spheroids. SGSC/ASC spheroids exhibited improved viability, calcium channel function, differentiation, and VEGF secretion after multiple, sequential stimulation. The 21-day survival rate of multiply stimulated SGSC/ASC spheroids was two-fold that of non-treated SGSC/ASC spheroids. Optimized SGSC/ASC spheroids enhanced the in vivo regeneration and functional recovery of SG tissue in mice by promoting neovascularization. Genes related to VEGF, such as Vegfa and Vegfb, were highly expressed 2∼6 times for in vitro and 1.5 times for in vivo experiment in the multiply stimulated SGSC/ASC spheroids. Therefore, SGSC/ASC spheroids that have undergone multiple stimulation may be useful for healing radiation-damaged SGs.
Keywords:Tissue engineering;Regenerative medicine;Three-dimensional;SpheroidXerostomia;Salivary gland;Salivary gland stem cell
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