Concise Review: The Potential Use of Intestinal Stem Cells to Treat Patients with Intestinal Failure.
Concise Review: The Potential Use of Intestinal Stem Cells to Treat Patients with Intestinal Failure.
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DOI：
10.5966/sctm.2016-0153
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发表时间：
2017-02
影响因子：
6
通讯作者：
Martín MG
中科院分区：
文献类型：
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作者：
Hong SN;Dunn JC;Stelzner M;Martín MG
肠衰竭是一种罕见的危及生命的疾病，导致仅通过肠内营养无法维持正常生长和水合状态。尽管肠外营养和全器官同种异体移植改善了这些患者的生存率，但目前的治疗与高发病率和死亡率风险相关。成人肠干细胞（ISCs）和多能干细胞增殖方法的发展提高了使用基于干细胞的治疗单基因和多基因形式肠衰竭患者的可能性。类器官已经证明了无限增殖和分化成肠道各种细胞谱系的能力。基因组编辑技术，包括缺陷基因的校正形式的过表达，或使用CRISPR（成簇规则间隔短回文重复序列）/Cas9选择性地校正干细胞内的单基因致病变体，使自体ISC移植成为可行的方法。然而，许多技术仍需要进一步优化，包括更稳健的离体ISC扩增、天然ISC消融和植入方案。大动物模型可用于开发此类技术和方案，并确定自体ISC移植的安全性，因为此类模型的结果更容易外推至人类。干细胞转化医学2017;6：666-676
Intestinal failure is a rare life‐threatening condition that results in the inability to maintain normal growth and hydration status by enteral nutrition alone. Although parenteral nutrition and whole organ allogeneic transplantation have improved the survival of these patients, current therapies are associated with a high risk for morbidity and mortality. Development of methods to propagate adult human intestinal stem cells (ISCs) and pluripotent stem cells raises the possibility of using stem cell‐based therapy for patients with monogenic and polygenic forms of intestinal failure. Organoids have demonstrated the capacity to proliferate indefinitely and differentiate into the various cellular lineages of the gut. Genome‐editing techniques, including the overexpression of the corrected form of the defective gene, or the use of CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 to selectively correct the monogenic disease‐causing variant within the stem cell, make autologous ISC transplantation a feasible approach. However, numerous techniques still need to be further optimized, including more robust ex vivo ISC expansion, native ISC ablation, and engraftment protocols. Large‐animal models can to be used to develop such techniques and protocols and to establish the safety of autologous ISC transplantation because outcomes in such models can be extrapolated more readily to humans. Stem Cells Translational Medicine 2017;6:666–676