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Cell Therapy for Kidney Injury: Different Options and Mechanisms - Mesenchymal and Amniotic Fluid Stem Cells

机译:肾脏损伤的细胞疗法:不同的选择和机制-间充质和羊水干细胞

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Background: Acute kidney injury (AKI) is emerging as a public health problem in developing and developed countries. It affects up to 7% of hospitalized patients, with a higher prevalence in critical care units. Despite major advances in preventive strategies and support measures, the mortality rate among patients remains higher than 50%. Several pharmacological approaches to improve renal function and survival after an AKI episode have been largely unsuccessful in clinical practice. Summary: Stem cell-based therapy has provided new hopes of innovative interventions to enhance the limited capability of kidney regeneration in AKI. An important target for cell therapy is represented by tubular epithelial cells which after acute ischemic or toxic insults undergo dysfunction and detachment. Among adult stem cells, mesenchymal stromal/stem cells (MSC) are an attractive therapeutic tool by virtue of their unique biological properties, tropism for damaged tissues, and proregenerative capacity. In the present review, we discuss the mechanisms underlying the renoprotective effects of therapies with stem cells of different origins in preclinical models of AKI by evaluating new modalities by which MSC interact with damaged cells via the release of soluble factors and exosomes/microvesi-cles. Several biological effects, including antiapoptotic,promitogenic, immunomodulatory, and anti-inflammatory activities, have been analyzed in renal tissue of AKI animals receiving stem cell treatments. The mechanisms of stem cell homing and engraftment to sites of tissue damage have also been discussed. Key Messages: The translation of preclinical data on stem cells into effective and safe new modalities of care is still limited, and further studies are needed before their application in patients with AKI.
机译:背景:急性肾损伤(AKI)在发展中国家和发达国家正在成为一种公共卫生问题。它影响高达7%的住院患者,重症监护病房的患病率更高。尽管预防策略和支持措施取得了重大进展,但患者的死亡率仍高于50%。在临床实践中,几种改善AKI发作后肾功能和存活的药理方法在很大程度上是不成功的。简介:基于干细胞的疗法为增强AKI肾脏再生能力的创新干预措施提供了新希望。细胞治疗的重要靶标是肾小管上皮细胞,其在急性缺血或毒性损伤后会发生功能障碍和脱离。在成体干细胞中,间充质基质/干细胞(MSC)凭借其独特的生物学特性,对受损组织的嗜性和促增殖能力而成为一种有吸引力的治疗工具。在本综述中,我们通过评估MSC通过释放可溶性因子和外泌体/微血管与受损细胞相互作用的新方式,探讨了AKI临床前模型中不同来源的干细胞对肾脏的保护作用机制。在接受干细胞治疗的AKI动物的肾脏组织中,已经分析了几种生物效应,包括抗凋亡,促proproogenic,免疫调节和抗炎活性。还讨论了干细胞归巢和植入组织损伤部位的机制。重要信息:将干细胞的临床前数据转化为有效且安全的新治疗方式仍然受到限制,在将其应用于AKI患者之前还需要进一步研究。

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