Preconditioning of the Liver for Efficient Repopulation by Primary Hepatocyte Transplants
Preconditioning of the Liver for Efficient Repopulation by Primary Hepatocyte Transplants
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DOI：
10.1007/978-1-4939-1453-1_3
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发表时间：
2014-01-01
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影响因子：
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通讯作者：
Koenig, Sarah
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文献类型：
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作者：
Krause, Petra;Rave-Frank, Margret;Koenig, Sarah
肝细胞移植的治疗潜力已在多项临床研究中得到证实，以纠正遗传性代谢或慢性肝病。然而，有几个突出的问题，这需要调查：最值得注意的供体细胞移植和随后的选择性扩增的transplantedcells.This协议描述了预处理的肝脏在二肽基肽酶-IV（DPPIV-）缺陷的大鼠模型的有效再利用选择性外照射技术结合区域短暂性门静脉缺血（RTPI）。照射宿主肝脏损害内源性细胞分裂，随后的RTPI构成了强烈的增殖刺激。移植的细胞受益于这种刺激，而内源性细胞由于宿主肝脏有丝分裂能力的降低而没有反应能力。如本文所述，肝再生的有效准备方案是外部束肝照射，其形式为单剂量25戈伊应用于整个器官，随后（4天后）对右肝叶进行RTPI，持续90 min。再灌注1 h后，供体肝细胞可直接移植到脾中作为植入部位，以进一步重新分配到门静脉系统和肝脏中。这种准备方案当然有可能在临床上实施，因为既不使用毒素，也不使用高度有效的致癌物。
The therapeutic potential of liver cell transplantation has been demonstrated in multiple clinical studies to correct hereditary metabolic or chronic liver diseases. However, there are several outstanding issues, which need to be investigated: most notably donor cell engraftment and the subsequent selective expansion of transplanted cells.This protocol describes the preconditioning of the liver in a dipeptidyl peptidase-IV (DPPIV-)deficient rat model of efficient repopulation utilizing a selective external beam irradiation technique combined with regional transient portal ischemia (RTPI). Irradiation of the host liver impairs endogenous cell division, and the subsequent RTPI constitutes a strongly proliferative stimulus. Transplanted cells benefit from this stimulus, whereas endogenous cells have no ability to respond, due to a reduction in the mitotic capacity of the host liver. As described here, an effective preparative regime for liver repopulation is external beam liver irradiation in the form of a single dose of 25 Gy applied to the whole organ followed (4 days later) by RTPI of the right liver lobes lasting 90 min. After 1 h of reperfusion, the donor hepatocytes may be transplanted directly into the spleen as implantation site for further redistribution into the portal system and liver. This preparative regime certainly has the potential to be implemented in the clinic, since neither toxins nor highly potent carcinogens are used.