Imberti Barbara, Tomasoni Susanna, Ciampi Osele, Pezzotta Anna, Derosas Manuela, Xinaris Christodoulos, Rizzo Paola, Papadimou Evangelia, Novelli Rubina, Benigni Ariela, Remuzzi Giuseppe, Morigi Marina
1] IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, 24126 Bergamo, ITALY [2] Fondazione IRCCS - Policlinico San Matteo, 27100 Pavia, ITALY.
IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, 24126 Bergamo, ITALY.
Sci Rep. 2015 Mar 6;5:8826. doi: 10.1038/srep08826.
Acute kidney injury (AKI) is one of the most relevant health issues, leading to millions of deaths. The magnitude of the phenomenon remarks the urgent need for innovative and effective therapeutic approaches. Cell-based therapy with renal progenitor cells (RPCs) has been proposed as a possible strategy. Studies have shown the feasibility of directing embryonic stem cells or induced Pluripotent Stem Cells (iPSCs) towards nephrogenic intermediate mesoderm and metanephric mesenchyme (MM). However, the functional activity of iPSC-derived RPCs has not been tested in animal models of kidney disease. Here, through an efficient inductive protocol, we directed human iPSCs towards RPCs that robustly engrafted into damaged tubuli and restored renal function and structure in cisplatin-mice with AKI. These results demonstrate that iPSCs are a valuable source of engraftable cells with regenerative activity for kidney disease and create the basis for future applications in stem cell-based therapy.
急性肾损伤（AKI）是最相关的健康问题之一，导致数百万例死亡。该现象的严重程度表明迫切需要创新且有效的治疗方法。利用肾祖细胞（RPCs）进行细胞治疗已被提出作为一种可能的策略。研究表明，将胚胎干细胞或诱导多能干细胞（iPSCs）定向分化为肾源性中间中胚层和后肾间充质（MM）是可行的。然而，iPSC来源的RPCs的功能活性尚未在肾脏疾病动物模型中进行测试。在此，通过一种高效的诱导方案，我们将人iPSCs定向分化为RPCs，这些RPCs能强有力地植入受损肾小管，并恢复顺铂诱导的急性肾损伤小鼠的肾功能和结构。这些结果表明，iPSCs是具有再生活性的可移植细胞的宝贵来源，可为肾脏疾病提供治疗，并为基于干细胞的治疗的未来应用奠定基础。
