1 Transplant Division, Department of Surgery, University of Texas Medical Branch Galveston, TX, USA.
2 Shriners Hospital for Children, University of Texas Medical Branch, Galveston, TX, USA.
Cell Transplant. 2017 Dec;26(12):1868-1877. doi: 10.1177/0963689717737320.
Attaining consistent robust engraftment in the structurally normal liver is an obstacle for cellular transplantation. Most experimental approaches to increase transplanted cells' engraftment involve recipient-centered deleterious methods such as partial hepatectomy or irradiation which may be unsuitable in the clinic. Here, we present a cell-based strategy that increases engraftment into the structurally normal liver using a combination of magnetic targeting and proliferative endoderm progenitor (EPs) cells. Magnetic labeling has little effect on cell viability and differentiation, but in the presence of magnetic targeting, it increases the initial dwell time of transplanted EPs into the undamaged liver parenchyma. Consequently, greater cell retention in the liver is observed concomitantly with fewer transplanted cells in the lungs. These highly proliferative cells then significantly increase their biomass over time in the liver parenchyma, approaching nearly 4% of total liver cells 30 d after transplant. Therefore, the cell-based mechanisms of increased initial dwell time through magnetic targeting combined with high rate of proliferation in situ yield significant engraftment in the undamaged liver.
在结构正常的肝脏中实现一致的稳健植入是细胞移植的一个障碍。大多数旨在增加移植细胞植入的实验方法都涉及以受者为中心的有害方法，如部分肝切除术或照射，这在临床上可能不合适。在这里，我们提出了一种基于细胞的策略，该策略使用磁靶向和增殖内胚层祖细胞 (EPs) 细胞的组合来增加结构正常肝脏中的植入。磁标记对细胞活力和分化几乎没有影响，但在磁靶向存在的情况下，它会增加移植的 EPs 进入未受损肝实质的初始停留时间。因此，在肺中观察到更少的移植细胞的同时，在肝脏中观察到更多的细胞保留。这些高度增殖的细胞随后在肝实质中随着时间的推移显著增加其生物量，在移植后 30 天接近总肝细胞的 4%。因此，通过磁靶向增加初始停留时间的基于细胞的机制与原位高增殖率相结合，可在未受损的肝脏中实现显著的植入。
