Placental stem cell correction of murine intermediate maple syrup urine disease.
Placental stem cell correction of murine intermediate maple syrup urine disease.
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DOI：
10.1002/hep.26150
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发表时间：
2013-03
期刊：
影响因子：
13.5
通讯作者：
Strom, Stephen C.
中科院分区：
文献类型：
--
作者：
Skvorak, Kristen J.;Dorko, Kenneth;Marongiu, Fabio;Tahan, Veysel;Hansel, Marc C.;Gramignoli, Roberto;Gibson, K. Michael;Strom, Stephen C.
我们之前报道了同种异体肝细胞移植后小鼠中间枫糖浆尿病（iMSUD）模型的生存率和部分代谢纠正的改善，证实了少量精通酶的肝移植细胞可以改善表型。然而，临床缺乏适合肝细胞分离的肝脏表明需要替代细胞来源。人羊膜上皮细胞（hAEC）具有干细胞的特征，但缺乏许多安全性和伦理问题，并向肝细胞样细胞分化。在出生后的前35天内，对iMSUD小鼠进行8例肝直接hAEC移植；饲喂正常蛋白质饲料，分别于第35天和第100天处死。新生儿阶段的治疗与MSUD的临床相关，并可能提供供体细胞植入的优势。与iMSUD相比，接受hAEC移植的iMSUD小鼠的生存期明显延长，体重正常化（严重病毒化，死亡≤28天）。支链α-酮酸脱氢酶活性显著升高。支链氨基酸亮氨酸、异亮氨酸、缬氨酸和异亮氨酸在血清和大脑中的含量显著提高，其他大型中性氨基酸也是如此。结论：胎盘源性干细胞移植延长了iMSUD小鼠模型的存活时间，并纠正了许多氨基酸失衡。这突出了它们作为MSUD和其他肝脏代谢性疾病的可行替代临床治疗方法的潜力。
We previously reported improved survival and partial metabolic correction of a mouse intermediate maple syrup urine disease (iMSUD) model post allogenic hepatocyte transplant, confirming that a small number of enzyme proficient liver-engrafted cells can improve phenotype. However, clinical shortages of suitable livers for hepatocyte isolation indicate a need for alternative cell sources. Human amnion epithelial cells (hAEC) share stem cell characteristics while lacking many safety and ethical concerns, and differentiate to hepatocyte-like cells. Eight direct hepatic hAEC transplants were administered to iMSUD mice over the first 35 days beginning at birth; animals were provided a normal protein diet and sacrificed at days 35 and 100. Treatment at the neonatal stage is clinically relevant for MSUD, and may offer a donor cell engraftment advantage. Survival was significantly extended and body weight was normalized in iMSUD mice receiving hAEC transplants compared to iMSUD (severely cachectic; dead ≤28 days). Branched chain α-keto acid dehydrogenase enzyme activity was significantly increased in transplanted livers. Branched chain amino acids leucine, isoleucine, valine, and alloisoleucine were significantly improved in the sera and brain, as were other large neutral amino acids. Conclusion: Placental-derived stem cell transplantation lengthened survival and corrected many amino acid imbalances in a mouse model of iMSUD. This highlights the potential for their use as a viable alternative clinical therapy for MSUD and other liver-based metabolic diseases.
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