基因君官网
2015年7月20日讯 /生物谷BIOON/ –近日，来自美国俄勒冈健康与科学大学的研究人员在著名国际学术期刊nature在线发表了一项最新研究进展，他们在利用全新的基因和干细胞疗法治疗线粒体疾病方面迈出了关键的第一步。
在美国，每年有1000～4000名新生儿患有线粒体DNA疾病，线粒体DNA突变会引起许多严重疾病的发生，其中包括糖尿病、耳聋、眼病、胃肠道疾病、心脏病、痴呆以及其他一些神经相关疾病。但到目前为止仍没有有效的方法能够对线粒体DNA相关疾病进行有效治疗。
在该项研究中，研究人员从一些携带线粒体DNA突变的儿童和成年人身上搜集了皮肤细胞，将皮肤细胞中的细胞核与健康捐赠者提供的卵细胞细胞质进行匹配，利用这种技术，研究人员获得了含有正常线粒体的胚胎干细胞。
他们希望在未来应用这种技术更正线粒体DNA突变，对健康细胞进行扩增之后重新导入到病人体内用以替代疾病组织。核移植技术相比于经典的基因治疗方法更加精确，并且不需要病毒载体对人工合成的DNA进行运送，更加安全。
领导该项研究的Shoukhrat Mitalipov这样说道：”我们现在可以对那些亲人患有线粒体疾病的家庭说，我们已经看到了线粒体疾病治愈的曙光。在过去的几年中我们一直致力于获得用于该类型疾病治疗的干细胞，而这项研究标志着我们已经在这条路上迈出了关键的第一步。利用基因和细胞联合治疗的方法可以避免器官捐赠出现的不匹配问题，在未来我们可以利用这项技术获得健康组织替代病人的疾病组织，同时不会出现排斥反应。”（基因宝jiyinbao.com）
Metabolic rescue in pluripotent cells from patients with mtDNA disease
Hong Ma,Clifford D. L. Folmes,Jun Wu,Robert Morey,Sergio Mora-Castilla, Alejandro Ocampo,Li Ma,Joanna Poulton,Xinjian Wang,Riffat Ahmed, Eunju Kang,Yeonmi Lee, Tomonari Hayama,Ying Li,Crystal Van Dyken,Nuria Marti Gutierrez,Rebecca Tippner-Hedges,Amy Koski,Nargiz Mitalipov,Paula Amato,Don P. Wolf,Taosheng Huang,Andre Terzic, Louise C. Laurent,Juan Carlos Izpisua Belmonte& Shoukhrat Mitalipov
Mitochondria have a major role in energy production via oxidative phosphorylation1, which is dependent on the expression of critical genes encoded by mitochondrial (mt)DNA. Mutations in mtDNA can cause fatal or severely debilitating disorders with limited treatment options2. Clinical manifestations vary based on mutation type and heteroplasmy (that is, the relative levels of mutant and wild-type mtDNA within each cell)3,4. Here we generated genetically corrected pluripotent stem cells (PSCs) from patients with mtDNA disease. Multiple induced pluripotent stem (iPS) cell lines were derived from patients with common heteroplasmic mutations including 3243A>G, causing mitochondrial encephalomyopathy and stroke-like episodes (MELAS)5, and 8993T>G and 13513G>A, implicated in Leigh syndrome. Isogenic MELAS and Leigh syndrome iPS cell lines were generated containing exclusively wild-type or mutant mtDNA through spontaneous segregation of heteroplasmic mtDNA in proliferating fibroblasts. Furthermore, somatic cell nuclear transfer (SCNT) enabled replacement of mutant mtDNA from homoplasmic 8993T>G fibroblasts to generate corrected Leigh-NT1 PSCs. Although Leigh-NT1 PSCs contained donor oocyte wild-type mtDNA (human haplotype D4a) that differed from Leigh syndrome patient haplotype (F1a) at a total of 47 nucleotide sites, Leigh-NT1 cells displayed transcriptomic profiles similar to those in embryo-derived PSCs carrying wild-type mtDNA, indicative of normal nuclear-to-mitochondrial interactions. Moreover, genetically rescued patient PSCs displayed normal metabolic function compared to impaired oxygen consumption and ATP production observed in mutant cells. We conclude that both reprogramming approaches offer complementary strategies for derivation of PSCs containing exclusively wild-type mtDNA, through spontaneous segregation of heteroplasmic mtDNA in individual iPS cell lines or mitochondrial replacement by SCNT in homoplasmic mtDNA-based disease.