Osman Yasser, Hamed Sahar M, Barakat Nashwa M, Khater Sherry, Gabr Mahmoud, Mosbah Ahmed, Gaballah Mohamed A, Shaaban Atallah
Urology and Nephrology Center, Mansoura University, Mansoura, Egypt.
Indian J Urol. 2020 Jan-Mar;36(1):44-49. doi: 10.4103/iju.IJU_114_19.
Stem cell therapy at the time of ischemia/reperfusion (I/R) injury has been hypothesized to attenuate the severity of acute kidney injury and to accelerate the regeneration process in lower animal models. Data in higher animal models is limited and discordant. We aimed to explore the reno-protective effects of stem cells on I/R related renal injury in a canine model.
Twenty-seven dogs that were treated with bone marrow-derived mesenchymal stem cells (BM-MSCs) were compared with another 27 dogs treated with adipose tissue-derived MSCs (AT-MSCs) following 90 min of warm ischemia to assess IR injury. Each group was divided into three subgroups (nine dogs each), according to the stem cell dose (5, 10, 15 × 10 in 500 μl volume) injected directly into the renal cortex after reperfusion. All dogs were re-evaluated by renogram, histopathology, and pro-inflammatory markers at 2 weeks, 2, and 3 months.
In Group I, there was a mean reduction of creatinine clearance by 78%, 64%, and 74% at the three used doses, respectively, at 2 weeks. At 3 months, these kidneys regained a mean of 84%, 92%, and 72%, respectively, of its basal function. In Group II, the reduction of clearance was much more modest with mean of 14%, 6%, and 24% respectively at 2 weeks with more intense recovery of renal function by mean of 90%, 100%, and 76%, respectively, at 3 months. Group I had significantly more tubular necrosis and delayed regeneration compared with the Group II. Expressions of pro-inflammatory markers were upregulated in both the groups with a higher and more sustained expression in Group I.
Stem cells protected against ischemic reperfusion injury in a canine model. AT-MSCs provided better protection than BM-MSCs.
在缺血/再灌注（I/R）损伤时进行干细胞治疗，据推测可减轻急性肾损伤的严重程度，并加速低等动物模型中的再生过程。高等动物模型中的数据有限且不一致。我们旨在探讨干细胞对犬模型中I/R相关肾损伤的肾脏保护作用。
将27只接受骨髓间充质干细胞（BM-MSCs）治疗的犬与另外27只在90分钟热缺血后接受脂肪组织来源的间充质干细胞（AT-MSCs）治疗的犬进行比较，以评估I/R损伤。每组根据再灌注后直接注入肾皮质的干细胞剂量（500μl体积中的5、10、15×10）分为三个亚组（每组9只犬）。在2周、2个月和3个月时，通过肾图、组织病理学和促炎标志物对所有犬进行重新评估。
在第一组中，在2周时，三种使用剂量下肌酐清除率平均分别降低了78%、64%和74%。在3个月时，这些肾脏分别恢复了其基础功能的84%、92%和72%。在第二组中，清除率的降低更为适度，2周时平均分别为14%、6%和24%，3个月时肾功能恢复更为显著，平均分别为90%、100%和76%。与第二组相比，第一组有更多的肾小管坏死和再生延迟。两组中促炎标志物的表达均上调，第一组中表达更高且更持久。
干细胞在犬模型中对缺血再灌注损伤具有保护作用。AT-MSCs比BM-MSCs提供了更好的保护。
