Ex vivo expansion of human pancreatic endocrine cells
Ex vivo expansion of human pancreatic endocrine cells
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DOI：
10.1210/jc.82.6.1852
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发表时间：
1997-06-01
影响因子：
5.8
通讯作者：
Hayek, A
中科院分区：
文献类型：
--
作者：
Beattie, GM;Cirulli, V;Hayek, A
作为1型糖尿病的疗法的细胞移植通过胰腺β细胞的离体细胞扩增而促进，而不丧失分化特征。本研究的目的是确定功能性人胰腺内分泌组织体外生长的最佳条件。我们研究了各种细胞系基质的促有丝分裂性;在膀胱癌细胞系基质上生长的细胞增殖更大，特别是在人细胞系HTB-9基质上生长的单层细胞中。培养14天后，有超过100倍的增殖增加，这是增加到超过200倍时，加入肝细胞生长因子/分散因子;然而，肝细胞生长因子/分散因子诱导胰岛素含量迅速下降。在没有生长因子的情况下，胎儿细胞单层扩增4倍，没有胰岛素损失;然而，在扩增12倍后，胰岛素水平下降到未扩增细胞的40%。成人胰岛细胞扩增3倍，无胰岛素损失。扩张5倍后，胰岛素水平与自由漂浮胰岛相比下降了25%，同时保持对促分泌素的正常反应。总之，这些结果表明HTB-9基质对人内分泌细胞的复制提供了最好的刺激作用，几乎没有体外功能的损失。
Cell transplantation as a therapy for type 1 diabetes is facilitated by ex vivo cell expansion of pancreatic beta-cells without loss of differentiative characteristics. The aim of this study was to determine the optimal conditions for in vitro growth of functional human pancreatic endocrine tissue. We examined the mitogenicity of matrixes from a variety of cell lines; proliferation was greater in cells growing on matrixes from bladder carcinoma cell lines, especially in monolayers grown on matrix from the human cell line HTB-9. After 14-day culture, there was a more than 100-fold proliferative increase, which was augmented to a more than 200-fold when hepatocyte growth factor/scatter factor was added; however, hepatocyte growth factor/scatter factor induced a rapid decrease in insulin content. Without the growth factor, fetal cell monolayers expanded 4-fold with no insulin loss; however, after 12-fold expansion, the insulin levels decreased to 40% of those in unexpanded cells. Adult islet cells expanded 3-fold without insulin loss. After 5-fold expansion, insulin levels decreased by 25% compared to those in free floating islets while retaining a normal response to secretagogues. Together, these results indicate that HTB-9 matrix provides the best stimulatory effect on replication of human endocrine cells, with little loss of in vitro function.