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Grow-your-own stem cells may repair Parkinson’s damage
A new stem cell therapy for Parkinson’s disease is one step closer to human trials after scientists were able to successfully rebuild neural damage in an animal model.
Researchers from Scripps Research and Cardiff University used induced pluripotent stem cells (iPSCs) from skin cells of two people with Parkinson’s disease to grow young neurons, which were then transplanted into rats with the degenerative condition. By timing the growth of the new cells just right, they’re able to replace the damaged neurons and potentially reverse the physical impairments that come with the neural damage.
While there are current stem cell clinical studies underway, this is the first one to make use of autologous therapy, which means the cells are harvested from the person who will ultimately receive the transplant.
"This paper reports important progress toward development of an autologous cell replacement therapy for Parkinson's disease," said senior author Jeanne Loring, professor at the Center for Regenerative Medicine at Scripps Research. "These results give us confidence that personalized therapy is feasible for Parkinson's disease."
Cells taken from foreign bodies require additional treatment, which can be very difficult on the patient.
"When you transplant neurons derived from someone else's cells, those cells will be rejected by the immune system, requiring the use of immunosuppressive drugs that are often not well tolerated,” Loring added.
The researchers were also able to determine at which stage in cell growth the transplant needed to occur, pinpointing the goldilocks moment in the iPSCs’ genetic development.
"At this earlier time point, the cells are poised to become neurons, and when they are put into the brain, they receive the signals to turn on those genes and finish their development,” said co-senior author Mariah Lelos. “This allows them to make connections with the host. “If they're farther along in development, they no longer respond to those initial developmental signals.”
While there’s no cure yet for Parkinson’s disease, effective neural therapy would be able to intervene in its progression and even reverse existing damage. Worldwide, around 10 million people are living with the disease and there are very limited options for treating the symptoms that can rob sufferers of their independence.
"Knowledge of which genes are turned on in neuronal precursors that are in the optimal developmental state to treat Parkinson's can help researchers screen cells before transplanting them into patients," Loring said. "The gene expression analysis should greatly improve the probability of successful transplants.”
Using the versatile 'universal' iPSCs, which have a broad range of cell differentiation potential, researchers believe this therapy could also inform new treatments for Huntington’s disease, heart failure and age-related macular degeneration.
注释：
pluripotent: adj
表示"[生]多能性的"，means ""，如：The mechanisms and ways to derivate pluripotent cells were reviewed. 对获得多能性干细胞所涉及的机制以及方法进行了综述。
degenerative: adj
表示"退化的；(疾病)变性的"，means "(of illness) marked by gradual deterioration of organs and cells along with loss of function;"，如：Degenerative changes of the myocardium occur in many diseases. 心肌的退化性变化发生于许多疾病。
autologous: adj
表示" 自体的；自身的"，means "derived from organisms of the selfsame individual"，如：The cost of autologous blood donation has receied recent attention. 术前贮存自体血的代价最近已引起注意。
immunosuppressive: adj
表示" 抑制免疫反应的"，means "of or relating to a substance that lowers the body's normal immune response and induces immunosuppression"，如：The use of new immunosuppressive drugs has further improved clinical results. 使用了新型的免疫抑制药物是取得好的临床效果的保证。
goldilocks: n
表示"至关重要；关键"，means ""，如：Few believe that Goldilocks will return. 这是至关重要的一步。
Precursors: n
表示" 先驱；前任；前兆"，means "something that precedes and indicates the approach of something or someone"，如：The precursor of the modern car was a horseless carriage with a petrol engine. 现代汽车的前身是不用马拉的，装有汽油发动机的车子。
macular：adj
表示" 有斑点的；有污点的"，如：What is age-related macular degeneration? 什么是老年性黄斑变性？
中文简要说明：
帕金森症(Parkinson's disease ,PD)是一种神经退化疾病，患者会出现肢体不易控制，最明显的特征就是手抖，目前尚无法治愈，但是科学家已提出一种干细胞修复办法，并且在动物模型中重建神经，距离人体试验又近了一步。
新阿特拉斯(New Altas)报导，全世界范围内，大约有 1000 万人患有这种疾病，相关的研究投资也没有中断过。皇天不复苦心人，美国史克里普斯研究中心(TSRI)和英国卡迪夫大学(Cardiff University)的研究人员，使用2名帕金森病患者皮肤细胞所制作的诱导多能干细胞（iPSC），来培养新生的神经元，然后将这些神经元移植到患有退行性疾病的老鼠体内。结果相当成功，这些新细胞在生长之后，能够取代受损的神经元，也就有可能逆转神经损伤。
虽然目前仅是干细胞临床实验，但是这是第一次利用自体干细疗法的研究，这意味着修复患者的干细胞，可以从患者身上采集，也就没有自体免疫排斥的问题，或是其他道德与法律的难题。
史克里普斯研究中心再生医学中心教授，也是论文作者珍妮•洛林博士（Jeanne Loring）说：「我们的论文提出了自体细胞治疗帕金森症的重要进展，这些结果让我们相信，个人式订制帕金森症疗法相当可行。」
研究人员攻克了一个难题，就是必须确定细胞生长到哪个阶段才适合移植。论文共同作者玛莉亚‧莱洛丝(Mariah Lelos)说：「我们现在知道在哪个时间点，干细胞准备成为神经元，此时将它们植入脑部以后，受到旁边其他脑细胞的信号，那些干细胞就会启动它们的内部基因，完成神经元的发育。如果培养的时间太长，使干细胞发育的太复杂，它们就不会再接收周边的发育讯号了。所以时间点很重要。」
洛林说：「这归功于我们对帕金森症已经累积了数十年的了解，使得我们能够掌握最佳发育状态的神经元，应该会大大提高移植成功的可能性。」
研究人员相信，在开启干细胞对帕金森症的神经修复之后，这种疗法还可以为亨廷顿跳舞症、心脏衰竭，和年龄性眼部黄斑细胞病变，提供相似的细胞修补疗法。
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