Potentiating Renal Regeneration Using Mesenchymal Stem Cells.
Potentiating Renal Regeneration Using Mesenchymal Stem Cells.
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DOI：
10.1097/tp.0000000000002455
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发表时间：
2019-03
期刊：
影响因子：
6.2
通讯作者：
Stubenitsky B
中科院分区：
文献类型：
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作者：
Brasile L;Henry N;Orlando G;Stubenitsky B
评估了间充质干细胞（MSC）治疗在24小时温灌注期间加速缺血损伤的人肾脏修复的潜力。假设是，通过将MSC直接给予肾组织，将有更好的机会通过肾内旁分泌效应介导细胞修复。使用失血性代谢支持（EMS）组织工程平台进行研究。本文报告了5对心源性死亡（DCD）供者的同种异体肾移植。一个人肾经EMS灌注24小时（对照），而其配对肾用MSC（1×108）进行EMS灌注。评价肾脏的DNA合成、细胞因子/趋化因子合成、细胞骨架再生和有丝分裂。MSC治疗导致肾脏合成的炎性细胞因子减少。MSC治疗导致ATP和生长因子的合成显著增加，导致代谢和细胞骨架正常化。MSC处理的肾的甲苯胺蓝染色表明，与单独的EMS灌注相比，经历有丝分裂的肾细胞的数量显著增加（26%）。据我们所知，我们的工作是第一个已经证明了实际的肾再生，而缺血损伤的人肾离体灌注24小时。观察到的再生需要：ATP合成增加，炎症反应减少，生长因子合成增加，细胞骨架和有丝分裂正常化。离体再生肾组织的能力足以导致立即的功能，可以通过解决慢性器官短缺来彻底改变移植。
The potential of a Mesenchymal Stem Cell (MSC) therapy to accelerate the repair of ischemically damaged human kidneys during 24 hours of warm perfusion was evaluated. The hypothesis was that by administering MSC directly to the renal tissue, there would be an improved opportunity for cellular repair mediated by intrarenal paracrine effects. Studies were performed using the Exsanguinous Metabolic Support (EMS) tissue-engineering platform. Five pairs of human kidney allografts from donation after cardiac death (DCD) donors were studied. One human kidney was EMS perfused for 24 hours (control), while its paired kidney was EMS perfused with MSC (1×108). The kidneys were evaluated for DNA synthesis, cytokine/chemokine synthesis, cytoskeletal regeneration and mitosis. Treatment with MSC resulted in reduced inflammatory cytokines synthesized by the kidneys. MSC treatment led to a significant increase in the synthesis of ATP and growth factors resulting in normalization of metabolism and the cytoskeleton. Toluidine Blue staining of MSC treated kidneys demonstrated a significant increase in the number of renal cells undergoing mitosis (26%) compared to EMS perfusion alone. To our knowledge, our work is the first to have demonstrated actual renal regeneration while ischemically damaged human kidneys are perfused ex vivo for 24 hours. The observed regeneration entails: increased synthesis of ATP, a reduced inflammatory response, increased synthesis of growth factors, normalization of the cytoskeleton and mitosis. The ability to regenerate renal tissue ex vivo sufficiently to result in immediate function could revolutionize transplantation by solving the chronic organ shortage.