Park Sang Eon, Kim Hyeong Seop, Kwon Soo Jin, Kim Min-Jeong, Choi Suk-Joo, Oh Soo-Young, Ryu Gyu Ha, Jeon Hong Bae, Na Duk L, Chang Jong Wook
Stem Cell Institute, ENCell Co. Ltd, Seoul 06072, Republic of Korea.
Stem Cell & Regenerative Medicine Institute, Samsung Medical Center, Seoul 06351, Republic of Korea.
Stem Cells Int. 2021 Mar 16;2021:6660186. doi: 10.1155/2021/6660186. eCollection 2021.
Mesenchymal stem cells (MSCs) have emerged as a promising tool for the treatment of Alzheimer's disease (AD). Previous studies suggested that the coculture of human MSCs with AD in an model reduced the expression of amyloid-beta 42 (A42) in the medium as well as the overexpression of amyloid-beta- (A-) degrading enzymes such as neprilysin (NEP). We focused on the role of primed MSCs (human Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) exposed to an AD cell line via a coculture system) in reducing the levels of A and inhibiting cell death. We demonstrated that mouse groups treated with naïve MSCs and primed MSCs showed significant reductions in cell death, ubiquitin conjugate levels, and A levels, but the effects were greater in primed MSCs. Also, mRNA sequencing data analysis indicated that high levels of TGF- induced primed-MSCs. Furthermore, treatment with TGF- reduced A expression in an AD transgenic mouse model. These results highlighted AD environmental preconditioning is a promising strategy to reduce cell death and ubiquitin conjugate levels and maintain the stemness of MSCs. Further, these data suggest that human WJ-MSCs exposed to an AD environment may represent a promising and novel therapy for AD.
间充质干细胞(MSCs)已成为治疗阿尔茨海默病(AD)的一种有前景的工具。先前的研究表明,在AD模型中,人MSCs与AD共培养可降低培养基中β淀粉样蛋白42(A42)的表达以及诸如中性内肽酶(NEP)等β淀粉样蛋白(Aβ)降解酶的过表达。我们聚焦于预处理的MSCs(通过共培养系统暴露于AD细胞系的人脐带华通氏胶来源的间充质干细胞(WJ-MSCs))在降低Aβ水平和抑制细胞死亡中的作用。我们证明,用未处理的MSCs和预处理的MSCs处理的小鼠组在细胞死亡、泛素缀合物水平和Aβ水平上均有显著降低,但预处理的MSCs效果更明显。此外,mRNA测序数据分析表明,高水平的转化生长因子-β(TGF-β)诱导了预处理的MSCs。此外,在AD转基因小鼠模型中,用TGF-β处理可降低Aβ表达。这些结果突出表明,AD环境预处理是一种有前景的策略,可减少细胞死亡和泛素缀合物水平,并维持MSCs的干性。此外,这些数据表明,暴露于AD环境的人WJ-MSCs可能代表一种有前景的新型AD治疗方法。