Meivar-Levy Irit, Sapir Tamar, Berneman Dana, Weissbach Tal, Polak-Charcon Sylvie, Ravassard Philippe, Tzakis Andreas G, Mor Eytan, Ricordi Camillo, Ferber Sarah
Sheba Regenerative Medicine, Stem cells and Tissue engineering Center, Sheba Medical Center, Tel-Hashomer 52621, Israel.
J Transplant. 2011;2011:252387. doi: 10.1155/2011/252387. Epub 2011 Aug 24.
Activation of the pancreatic lineage in the liver has been suggested as a potential autologous cell replacement therapy for diabetic patients. Transcription factors-induced liver-to-pancreas reprogramming has been demonstrated in numerous species both in vivo and in vitro. However, human-derived liver cells capable of acquiring the alternate pancreatic repertoire have never been characterized. It is yet unknown whether hepatic-like stem cells or rather adult liver cells give rise to insulin-producing cells. Using an in vitro experimental system, we demonstrate that proliferating adherent human liver cells acquire mesenchymal-like characteristics and a considerable level of cellular plasticity. However, using a lineage-tracing approach, we demonstrate that insulin-producing cells are primarily generated in cells enriched for adult hepatic markers that coexpress both albumin and mesenchymal markers. Taken together, our data suggest that adult human hepatic tissue retains a substantial level of developmental plasticity, which could be exploited in regenerative medicine approaches.
肝脏中胰腺谱系的激活已被提议作为糖尿病患者潜在的自体细胞替代疗法。转录因子诱导的肝脏向胰腺重编程已在许多物种的体内和体外得到证实。然而，能够获得替代胰腺细胞谱的人源肝细胞从未被鉴定过。目前尚不清楚是肝样干细胞还是成体肝细胞产生胰岛素分泌细胞。利用体外实验系统，我们证明增殖的贴壁人肝细胞获得间充质样特征和相当程度的细胞可塑性。然而，使用谱系追踪方法，我们证明胰岛素分泌细胞主要在富含同时表达白蛋白和间充质标记物的成体肝脏标记物的细胞中产生。综上所述，我们的数据表明成人肝脏组织保留了相当程度的发育可塑性，这可在再生医学方法中加以利用。
