Department of Nephrology, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
Department of Stem Cell Biology and Medicine, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
Int J Mol Sci. 2021 Apr 17;22(8):4178. doi: 10.3390/ijms22084178.
Mesenchymal stem cells (MSCs) are a potential therapeutic tool for preventing the progression of acute kidney injury (AKI) to chronic kidney disease (CKD). Herein, we investigated the localization and maintenance of engrafted human bone marrow-derived MSCs in rats subjected to a renal ischemia-reperfusion injury (IRI) and compared the effectiveness of two intravascular injection routes via the renal artery or inferior vena cava. Renal artery injection of MSCs was more effective than intravenous injection at reducing IRI-induced renal fibrosis. Additionally, MSCs injected through the renal artery persisted in injured kidneys for over 21 days, whereas MSCs injected through the inferior vena cava survived for less than 7 days. This difference may be attributed to the antifibrotic effects of MSCs. Interestingly, MSCs injected through the renal artery were localized primarily in glomeruli until day 3 post-IRI, and they decreased in number thereafter. In contrast, the number of MSCs localized in tubular walls, and the interstitium increased gradually until day 21 post-IRI. This localization change may be related to areas of damage caused by IRI because ischemia-induced AKI leads to tubular cell damage. Taken together, these findings suggest renal artery injection of MSCs may be useful for preventing the progression of AKI to CKD.
间充质干细胞（MSCs）是一种潜在的治疗工具，可用于防止急性肾损伤（AKI）进展为慢性肾脏病（CKD）。在此，我们研究了骨髓源性人 MSCs 在肾缺血再灌注损伤（IRI）大鼠中的定位和维持情况，并比较了经肾动脉或下腔静脉两种血管内注射途径的效果。与静脉内注射相比，MSCs 经肾动脉注射更能有效减少 IRI 诱导的肾纤维化。此外，经肾动脉注射的 MSCs 在损伤肾脏中持续存在超过 21 天，而经下腔静脉注射的 MSCs 存活时间不到 7 天。这种差异可能归因于 MSCs 的抗纤维化作用。有趣的是，经肾动脉注射的 MSCs 在 IRI 后第 3 天主要定位于肾小球，此后数量减少。相比之下，定位于肾小管壁和间质的 MSC 数量逐渐增加，直到 IRI 后第 21 天。这种定位变化可能与 IRI 引起的损伤区域有关，因为缺血性 AKI 会导致肾小管细胞损伤。综上所述，这些发现表明，MSCs 经肾动脉注射可能有助于预防 AKI 进展为 CKD。
