Hepatic targeting and biodistribution of human fetal liver stem/progenitor cells and adult hepatocytes in mice.
Hepatic targeting and biodistribution of human fetal liver stem/progenitor cells and adult hepatocytes in mice.
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DOI：
10.1002/hep.23120
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发表时间：
2009-10
期刊：
影响因子：
13.5
通讯作者：
Gupta, Sanjeev
中科院分区：
文献类型：
--
作者：
Cheng, Kang;Benten, Daniel;Bhargava, Kuldeep;Inada, Mari;Joseph, Brigid;Palestro, Christopher;Gupta, Sanjeev
通过非侵入性成像跟踪干细胞/祖细胞是评估移植细胞靶向特定器官的有用手段。我们进行了体外和体内研究，其中成人肝细胞和人胎肝干/祖细胞用铟-111(111In)-奥辛和~(99m)Tm(99mTC)-UTERATAG或99mTC-Ceretec标记。对异种耐受非肥胖型糖尿病/重度联合免疫缺陷小鼠经脾内和门静脉途径移植后，体外分析细胞的标记效率和活性，并分析细胞在体内的器官生物分布。我们发现成人肝细胞和胎肝干/祖细胞可结合~(111)In，但不能标记~(99m)Tc。放射性标记后，细胞存活率没有变化。移植的成人肝细胞或胎肝干/祖细胞通过门脉内而不是脾内途径更有效地靶向肝脏。移植细胞在门静脉注射后留在肝脏内，在脾内注射后留在肝和脾内，没有移位到肺或体循环中。与胎肝干/祖细胞相比，脾内移植后保留在脾内的成体肝细胞较少。移植细胞在器官中的分布通过遗传学分析得到证实，包括从灵长类特有的Charcot-Marie-Tooth元件中扩增DNA序列，以及原位杂交灵长类阿尔菲卫星序列，这些序列普遍存在于所有着丝粒中。111In标记人胎肝干/祖细胞和成人肝细胞对移植细胞的无创性定位是有效的。这应该有助于通过进一步的动物和临床研究来继续开发细胞疗法。
Tracking stem/progenitor cells through noninvasive imaging is a helpful means of assessing the targeting of transplanted cells to specific organs. We performed in vitro and in vivo studies wherein adult human hepatocytes and human fetal liver stem/progenitor cells were labeled with indium-111 (111In)-oxine and technetium-99m (99mTc)-Ultratag or 99mTc-Ceretec. The labeling efficiency and viability of cells was analyzed in vitro, and organ biodistribution of cells was analyzed in vivo after transplantation in xenotolerant nonobese diabetic/severe combined immunodeficiency mice through intrasplenic or intraportal routes. We found that adult hepatocytes and fetal liver stem/progenitor cells incorporated 111In but not 99mTc labels. After radiolabeling, cell viability was unchanged. Transplanted adult hepatocytes or fetal liver stem/progenitor cells were targeted to the liver more effectively by the intraportal rather than the intrasplenic route. Transplanted cells were retained in the liver after intraportal injection and in the liver and spleen after intrasplenic injection, without translocations into pulmonary or systemic circulations. Compared with fetal liver stem/progenitor cells, fewer adult hepatocytes were retained in the spleen after intrasplenic transplantation. The distribution of transplanted cells in organs was substantiated by genetic assays, including polymerase chain reaction amplification of DNA sequences from a primate-specific Charcot-Marie-Tooth element, and in situ hybridization for primate alphoid satellite sequences ubiquitous in all centromeres. 111In labeling of human fetal liver stem/progenitor cells and adult hepatocytes was effective for noninvasive localization of transplanted cells. This should facilitate continued development of cell therapies through further animal and clinical studies.
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影响因子：
4.8
作者：
Gupta, S;Rajvanshi, P;Gorla, GR
通讯作者：
Gorla, GR
影响因子：
25.7
作者：
Rajvanshi, P;Fabrega, A;Gupta, S
通讯作者：
Gupta, S
影响因子：
6.6
作者：
Inada, Mari;Benten, Daniel;Gupta, Sanjeev
通讯作者：
Gupta, Sanjeev
影响因子：
13.5
作者：
GUPTA, S;LEE, CD;BHARGAVA, KK
通讯作者：
BHARGAVA, KK
影响因子：
4.2
作者：
GUPTA, S;YERNENI, PR;BHARGAVA, KK
通讯作者：
BHARGAVA, KK