年前，美国威斯康星大学的詹姆斯·汤姆逊从人的胚胎干细胞中分离出了干细胞。干细胞是一种未充分分化、尚不成熟的细胞，具有再生各种组织器官和人体的潜在功能，医学界将其称为“万用细胞”。这表明，人体内衰竭或受损的身体组织都能被修复，疾病也因此能得以治疗。有鉴于此，以干细胞治疗为基础的再生医疗技术慢慢开始进入大众视野并为大众所熟知。
然而，由于胚胎干细胞要从胚胎中提取，因此涉及伦理和道德问题，有关研究遇到了不少反对声音，干细胞领域的技术发展也不断遭遇挫折，干细胞技术领域的进步也一直让人如“雾里看花”。不过，英国《经济学人》杂志网站近日报道称，最近发表的两篇新论文证明，干细胞领域确实取得了一些进步。
胚胎干细胞有助于治疗失明
美国加州大学洛杉矶分校的斯蒂芬·施华兹近日在英国著名的《柳叶刀》杂志发表论文指出，他们使用人的胚胎干细胞进行的临床结果表明，干细胞技术对治疗失明有帮助。施华兹的研究受到了美国先进细胞技术公司的资助。
他们的研究对象为两名失明患者。一名病人罹患了老年性黄斑变性，这是发生于中老年人中的致盲性眼病之一，也是发达国家导致人失明的“罪魁祸首”；另一名病人则罹患斯特格氏症，这种疾病又称少年黄斑变性，是一种遗传性眼病，患者的最终视力一般只有0.1左右，极少数会完全失明，主要病因是基因异常导致感光细胞退化，目前尚无有效疗法。
在研究中，施华兹团队首先诱导胚胎干细胞变成为视网膜色素上皮，视网膜色素上皮是支撑视杆细胞和视锥细胞的组织，而视杆细胞和视锥细胞实际上是眼睛内对光线做出反应的细胞。接着，施华兹团队将5万个视网膜色素上皮注入每名病人的一只眼睛中，希望它们促进这些细胞的自然供应。
结果，他们的实验获得了部分成功。首先，两名病人都没有对移植产生排斥反应，一直以来，排斥反应都是将外来器官或组织移入人体内的主要风险。第二，尽管两名病人的视力都没有得到很大恢复，但移植手术进行4个月后，两名病人都能够辨识出更多字母。
干细胞技术有助于专家洞悉疾病
施华兹团队的技术是否真的有用还有待时间考验。但是，第二篇发表于《自然》杂志、由加州大学圣地亚哥分校的劳伦斯·戈尔茨坦和同事发表的论文表明，即使不直接用于治疗，干细胞也是有用的，有助于科学家们对疾病获得更加深入的了解。
自从2006年开始，科学家们已经能够使用名为转录因子的蛋白质，对成人细胞重新编程让其进入胚胎状态，尽管这些经过重新编程的细胞——诱导多能干细胞（iPS细胞）终有一天能被用于治疗，但它们的即时价值在于，它们是一种理解疾病的好方式。科学家们能使用iPS细胞培育出与身体内已受损的细胞一模一样的纯细胞。
因此，戈尔茨坦也在借用iPS细胞认识阿尔茨海默症。晚期阿尔茨海默症患者的脑神经细胞外会出现β-淀粉样蛋白聚集的老年斑，β-淀粉样蛋白可干扰细胞与细胞之间神经突触所发的信号，也可激活胶质细胞引起过度炎症反应，杀伤健康的神经细胞。另外一个症状是患者脑神经细胞内Tau蛋白异常聚集形成神经纤维缠结。
但是，这些老年斑以及缠结如何相关却一直是个未解之谜。为此，戈尔茨坦从6个人体内提取了组织，其中两人罹患普通的阿尔茨海默症，这是由已知的遗传变异导致的一种罕见的疾病形式；另外两人罹患散发性阿尔茨海默症，造成这种疾病的直接原因还不清楚；还有两名没有罹患阿尔茨海默症的病人则作为控制组。
戈尔茨坦对收集到的细胞进行了重新编程，让其变成了iPS细胞，接着向前一步，让其变成了神经细胞。
结果表明，这些实验室制造出来的神经细胞确实让4名罹患阿尔茨海默症的病人中的3名展示出了高浓度的β-淀粉样蛋白和Tau蛋白以及一种活性酶GSK3-beta。因为戈尔茨坦的细胞是培育而来，因此，他能调查这三者之间的关系。
为了做到这一点，他对这些培育的细胞进行了处理。结果发现，能够直接诱发β-淀粉样蛋白的一种药物并不会导致更低浓度的Tau蛋白或者活性酶GSK3-beta，但是，一种攻击β-淀粉样蛋白的前体分子的药物确实会导致更低浓度的Tau蛋白或者活性酶GSK3-beta。这是有用的信息，因为它表明，采用药物对付这种疾病最好要攻击何处。
至少从短期来看，与施华兹团队进行的临床实验相比，尽管这类基于iPS细胞的研究本身并不用于治疗，但却很可能提供更多的科学价值。然而要做到这一点，科学家们需要更多的多能干细胞。有鉴于此，汤姆逊创建了一家公司，销售科学家们用于研究所需要的数量庞大的多能干细胞。(生物谷 Bioon.com)
doi:10.1016/S0140-6736(12)60028-2
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Embryonic stem cell trials for macular degeneration: a preliminary report
Prof Steven D Schwartz , Jean-Pierre Hubschman, Gad Heilwell, Valentina Franco-Cardenas, Carolyn K Pan, Rosaleen M Ostrick MPH, Edmund Mickunas, Roger Gay, Irina Klimanskaya , Dr Robert Lanza
Background
It has been 13 years since the discovery of human embryonic stem cells (hESCs). Our report provides the first description of hESC-derived cells transplanted into human patients.
Methods
We started two prospective clinical studies to establish the safety and tolerability of subretinal transplantation of hESC-derived retinal pigment epithelium (RPE) in patients with Stargardt's macular dystrophy and dry age-related macular degeneration—the leading cause of blindness in the developed world. Preoperative and postoperative ophthalmic examinations included visual acuity, fluorescein angiography, optical coherence tomography, and visual field testing. These studies are registered with ClinicalTrials.gov, numbers NCT01345006 and NCT01344993.
Findings
Controlled hESC differentiation resulted in greater than 99% pure RPE. The cells displayed typical RPE behaviour and integrated into the host RPE layer forming mature quiescent monolayers after transplantation in animals. The stage of differentiation substantially affected attachment and survival of the cells in vitro after clinical formulation. Lightly pigmented cells attached and spread in a substantially greater proportion (>90%) than more darkly pigmented cells after culture. After surgery, structural evidence confirmed cells had attached and continued to persist during our study. We did not identify signs of hyperproliferation, abnormal growth, or immune mediated transplant rejection in either patient during the first 4 months. Although there is little agreement between investigators on visual endpoints in patients with low vision, it is encouraging that during the observation period neither patient lost vision. Best corrected visual acuity improved from hand motions to 20/800 (and improved from 0 to 5 letters on the Early Treatment Diabetic Retinopathy Study [ETDRS] visual acuity chart) in the study eye of the patient with Stargardt's macular dystrophy, and vision also seemed to improve in the patient with dry age-related macular degeneration (from 21 ETDRS letters to 28).
Interpretation
The hESC-derived RPE cells showed no signs of hyperproliferation, tumorigenicity, ectopic tissue formation, or apparent rejection after 4 months. The future therapeutic goal will be to treat patients earlier in the disease processes, potentially increasing the likelihood of photoreceptor and central visual rescue.
Funding
Advanced Cell Technology.
doi:10.1038/nature10821
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Probing sporadic and familial Alzheimer’s disease using induced pluripotent stem cells
Mason A. Israel, Shauna H. Yuan,, Cedric Bardy, Sol M. Reyna,, Yangling Mu, Cheryl Herrera, Michael P. Hefferan, Sebastiaan Van Gorp, Kristopher L. Nazor, Francesca S. Boscolo, Christian T. Carson, Louise C. Laurent, Martin Marsala,, Fred H. Gage, Anne M. Remes, Edward H. Koo & Lawrence S. B. Goldstein,
Our understanding of Alzheimer’s disease pathogenesis is currently limited by difficulties in obtaining live neurons from patients and the inability to model the sporadic form of the disease. It may be possible to overcome these challenges by reprogramming primary cells from patients into induced pluripotent stem cells (iPSCs). Here we reprogrammed primary fibroblasts from two patients with familial Alzheimer’s disease, both caused by a duplication of the amyloid-β precursor protein gene (APP; termed APPDp), two with sporadic Alzheimer’s disease (termed sAD1, sAD2) and two non-demented control individuals into iPSC lines. Neurons from differentiated cultures were purified with fluorescence-activated cell sorting and characterized. Purified cultures contained more than 90% neurons, clustered with fetal brain messenger RNA samples by microarray criteria, and could form functional synaptic contacts. Virtually all cells exhibited normal electrophysiological activity. Relative to controls, iPSC-derived, purified neurons from the two APPDp patients and patient sAD2 exhibited significantly higher levels of the pathological markers amyloid-β(1–40), phospho-tau(Thr 231) and active glycogen synthase kinase-3β (aGSK-3β). Neurons from APPDp and sAD2 patients also accumulated large RAB5-positive early endosomes compared to controls. Treatment of purified neurons with β-secretase inhibitors, but not γ-secretase inhibitors, caused significant reductions in phospho-Tau(Thr 231) and aGSK-3β levels. These results suggest a direct relationship between APP proteolytic processing, but not amyloid-β, in GSK-3β activation and tau phosphorylation in human neurons. Additionally, we observed that neurons with the genome of one sAD patient exhibited the phenotypes seen in familial Alzheimer’s disease samples. More generally, we demonstrate that iPSC technology can be used to observe phenotypes relevant to Alzheimer’s disease, even though it can take decades for overt disease to manifest in patients.
