Kasarinaite Alvile, Hay David C
Institute for Regeneration and Repair, Centre for Regenerative Medicine, The University of Edinburgh, Edinburgh, UK.
Methods Mol Biol. 2025;2924:145-161. doi: 10.1007/978-1-0716-4530-7_11.
Alterations in cellular metabolism are a major contributor to the worldwide obesity crisis. Numerous defects underpin this disease, and a major contributor is the development of metabolic dysfunction associated with steatotic liver disease (MASLD). This can lead to the progressive form of liver disease termed Metabolic Dysfunction Associated Steatohepatitis (MASH) and this can lead to end-stage liver disease (Wong VWS, Adams LA, de Ledinghen V et al, Nat Rev Gastroenterol Hepatol 8:461-478, 2018). While liver transplantation is highly successful at treating end-stage liver disease, it is severely limited by organ donation and limited by the requirement for life-long immunosuppression. Therefore, to better understand the disease, and identify new biomarkers, and therapeutics for MASLD/MASH, new human cell-based models are required (Wong VWS, Adams LA, de Ledinghen V et al, Nat Rev Gastroenterol Hepatol 8:461-478, 2018). Therefore, we have developed a scalable liver tissue engineering platform from induced pluripotent stem cells (iPSCs) to study human liver metabolic disease in vitro.
细胞代谢改变是全球肥胖危机的主要促成因素。这种疾病存在众多缺陷，其中一个主要因素是与脂肪性肝病相关的代谢功能障碍（MASLD）的发展。这可能导致称为代谢功能障碍相关脂肪性肝炎（MASH）的进行性肝病形式，进而可能导致终末期肝病（Wong VWS、Adams LA、de Ledinghen V等，《自然综述：胃肠病学与肝病学》8:461 - 478，2018年）。虽然肝移植在治疗终末期肝病方面非常成功，但它受到器官捐赠的严重限制，并且受到终身免疫抑制需求的限制。因此，为了更好地理解这种疾病，并确定MASLD/MASH的新生物标志物和治疗方法，需要新的基于人类细胞的模型（Wong VWS、Adams LA、de Ledinghen V等，《自然综述：胃肠病学与肝病学》8:461 - 478，2018年）。因此，我们已经从诱导多能干细胞（iPSC）开发了一个可扩展的肝组织工程平台，用于在体外研究人类肝脏代谢疾病。
