Nowacki Maciej, Nazarewski Łukasz, Pokrywczyńska Marta, Kloskowski Tomasz, Tyloch Dominik, Pietkun Katarzyna, Jundziłł Arkadiusz, Rasmus Marta, Warda Karolina, Gagat Maciej, Grzanka Alina, Bodnar Magdalena, Marszałek Andrzej, Krawczyk Marek, Habib Samy L, Drewa Tomasz
Chair of Regenerative Medicine, Department of Tissue Engineering, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Bydgoszcz, Poland.
Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland.
Ann Transplant. 2015 Mar 10;20:132-40. doi: 10.12659/AOT.892364.
The aim of this study was to evaluate the long-term usefulness of intraportal injection of the bone marrow-derived mesenchymal stem cells (BM-MSCs) in limitation of experimentally induced ischemia-reperfusion injury (IRI) in a rat model.
Twenty Wistar rats were divided into 3 groups: donor group (n=5), study group (n=10), and control group (n=5). IRI was performed using a modified hanging-weight system after left portal triad occlusion in study group animals. Isolated autologous BM-MSCs were labeled with fluorochrome PKH-26 then intraportally injected into the rats in the study group. Control group animals were intraportally injected with 1 ml of PBS. Follow-up was 3 months, after which animals were sacrificed for histopathological examination. Migration of BM-MSCs into different organs was examined.
H&E staining of liver tissue sections from "time zero" biopsies did not show many irregularities in structural or histological construction compared to liver sections from the control group. However, a small amount of centrilobular hepatocyte necrosis and coagulative necrosis with neutrophil infiltration areas was observed in liver sections of the study group. The migration assay of BM-MSCs labeled with PKH-26 showed the highest positive BM-MSCs staining (6%) in the spleen, while few positively stained cells were found (2%) in liver sections. No BM-MSCs were detected in brain, kidney, or lung tissues.
These results suggest that intraportal bone marrow-derived mesenchymal stem cell injection is safe and cells do not migrate chaotically to other organs after targeted implementation.
本研究旨在评估门静脉内注射骨髓间充质干细胞(BM-MSCs)对大鼠实验性缺血再灌注损伤(IRI)的长期作用。
将20只Wistar大鼠分为3组:供体组(n = 5)、研究组(n = 10)和对照组(n = 5)。研究组动物在左门静脉三联结扎后,使用改良的悬挂重量系统进行IRI。分离的自体BM-MSCs用荧光染料PKH-26标记,然后经门静脉注射到研究组大鼠体内。对照组动物经门静脉注射1 ml PBS。随访3个月,之后处死动物进行组织病理学检查。检测BM-MSCs向不同器官的迁移情况。
与对照组肝脏切片相比,“零时”活检的肝脏组织切片的苏木精-伊红(H&E)染色在结构或组织学构建上未显示出许多异常。然而,研究组肝脏切片中观察到少量小叶中央肝细胞坏死和伴有中性粒细胞浸润区域的凝固性坏死。用PKH-26标记的BM-MSCs迁移试验显示,脾脏中BM-MSCs阳性染色最高(6%),而在肝脏切片中发现的阳性染色细胞很少(2%)。在脑、肾或肺组织中未检测到BM-MSCs。
这些结果表明,门静脉内注射骨髓间充质干细胞是安全的,且细胞在靶向注射后不会无序迁移至其他器官。