Efficacy of engineered liver tissue based on poly-L-lactic acid scaffolds and fetal mouse liver cells cultured with oncostatin M, nicotinamide, and dimethyl sulfoxide.

Efficacy of engineered liver tissue based on poly-L-lactic acid scaffolds and fetal mouse liver cells cultured with oncostatin M, nicotinamide, and dimethyl sulfoxide.
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DOI:
10.1089/ten.2004.10.1577
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发表时间:
2004-11
期刊:
影响因子:
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通讯作者:
Jinlan Jiang;N. Kojima;Lei Guo;K. Naruse;M. Makuuchi;A. Miyajima;Weiqun Yan;Y. Sakai
Jinlan Jiang;N. Kojima;Lei Guo;K. Naruse;M. Makuuchi;A. Miyajima;Weiqun Yan;Y. Sakai
中科院分区:
生物2区
文献类型:
--
作者:
Jinlan Jiang;N. Kojima;Lei Guo;K. Naruse;M. Makuuchi;A. Miyajima;Weiqun Yan;Y. Sakai

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为了评估基于肝细胞祖细胞在三维(3D)培养中的选择性增殖和分化的肝组织等效物的可行性,在体外和体内研究了在烟酰胺、二甲亚砜和制瘤素M存在下在聚-L-乳酸(PLLA)支架中培养的胎鼠肝细胞的功效。在这三种因素存在的情况下,PLLA培养的胎鼠肝细胞的白蛋白产量随着培养时间的推移而显着增加,4周后,根据单位DNA量,其产量几乎与在PLLA支架中培养3天的成年小鼠肝细胞相同。此外,将基于该体外PLLA培养系统的工程化肝组织植入70%肝切除小鼠的腹腔中,与新鲜分离并培养1天的胎鼠肝细胞或成年小鼠肝细胞相比,在手术后15天显示出明显更高的白蛋白阳性移植细胞的存在。这些结果表明,基于体外选择性增殖和分化的肝细胞祖细胞在3D生物可降解支架的肝组织工程的基本概念,为未来的肝组织工程显示了希望。
To assess the feasibility of liver tissue equivalents based on selective propagation and differentiation of hepatocyte progenitors in three-dimensional (3D) culture, the efficacy of fetal mouse liver cells cultured in poly-L-lactic acid (PLLA) scaffolds in the presence of nicotinamide, dimethyl sulfoxide, and oncostatin M was investigated both in vitro and in vivo. The albumin production of PLLA-cultured fetal mouse liver cells in the presence of these three factors was remarkably enhanced with culture time, and after 4 weeks it attained almost the same production found in adult mouse hepatocytes cultured for 3 days in PLLA scaffolds, based on the unit DNA amount. In addition, implantation of engineered liver tissue based on this in vitro PLLA culture system into the peritoneal cavity of 70% hepatectomized mice showed a remarkably higher presence of albumin-positive engrafted cells 15 days after the operation when compared with fetal mouse liver cells or adult mouse hepatocytes freshly isolated and cultured for 1 day. These results demonstrate that the basic concept regarding the engineering of liver tissue equivalents based on in vitro selective propagation and differentiation of hepatocyte progenitors in 3D biodegradable scaffolds shows promise for future liver tissue engineering.