干細胞移植恢復大腦記憶
近日，復旦大學張素春團隊首次將人類胚胎干細胞成功轉(zhuǎn)化成特定的神經(jīng)細胞，并將轉(zhuǎn)化后的中間細胞注入到小鼠大腦中，使已喪失學習和記憶功能的小鼠恢復了學習和記憶能力。近日，相關(guān)研究成果發(fā)表于最新一期的學術(shù)期刊《Nature Biotechnol 自然 生物技術(shù)》。業(yè)內(nèi)專家認為，該成果對治愈各種神經(jīng)功能缺陷疾病有重大意義。
據(jù)介紹，張素春科研團隊選中了一種不會排斥其他物種移植物的特殊小鼠，他們首先“蓄意破壞”了小鼠大腦中掌管“學習和記憶”、被稱為“內(nèi)側(cè)隔核”的大腦區(qū)域的“線路”，使小鼠暫時喪失“學習和記憶”能力。
然后，研究人員利用化學方法將人類胚胎干細胞轉(zhuǎn)化成神經(jīng)細胞，并將這些轉(zhuǎn)化后的中間細胞移植到小鼠大腦中。張素春說，這一過程有點類似于拆除一段電話線，之后你如果能找到正確的線路，需要時就能夠把“斷線”接上。
于是，研究人員將細胞移植到了小鼠記憶回路的另一端――大腦記憶中心海馬內(nèi)。植入后的干細胞立刻形成兩種常見的、重要的神經(jīng)元類型，它們分別與化學物質(zhì)γ-氨基丁酸或乙酰膽堿能神經(jīng)元進行有效溝通，并響應(yīng)來自大腦的化學指令，開始特化并與海馬中的適當細胞相連接。
測試證實，這些接受干細胞移植后“連接”成功的小鼠，常規(guī)學習和記憶能力得到了有效恢復，評分明顯優(yōu)于那些依然喪失“學習和記憶”能力的小鼠。
該研究的終極目標是通過細胞替代來修復大腦損傷并將有可能馬上應(yīng)用于構(gòu)建藥物篩查的模型，并為將來治愈各種神經(jīng)功能缺陷疾病帶來希望。
推薦原文閱讀：
Nat Biotechnol. 2013 May;31(5):440-7. doi: 10.1038/nbt.2565. Epub 2013 Apr 21.
Medial ganglionic eminence-like cells derived from human embryonic stem cells correct learning and memory deficits.
Liu Y, Weick JP, Liu H, Krencik R, Zhang X, Ma L, Zhou GM, Ayala M, Zhang SC.
SourceWaisman Center, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin, USA.
Abstract
Dysfunction of basal forebrain cholinergic neurons (BFCNs) and γ-aminobutyric acid (GABA) interneurons, derived from medial ganglionic eminence (MGE), is implicated in disorders of learning and memory. Here we present a method for differentiating human embryonic stem cells (hESCs) to a nearly uniform population of NKX2.1(+) MGE-like progenitor cells. After transplantation into the hippocampus of mice in which BFCNs and some GABA neurons in the medial septum had been destroyed by mu P75-saporin, human MGE-like progenitors, but not ventral spinal progenitors, produced BFCNs that synaptically connected with endogenous neurons, whereas both progenitors generated similar populations of GABA neurons. Mice transplanted with MGE-like but not spinal progenitors showed improvements in learning and memory deficits. These results suggest that progeny of the MGE-like progenitors, particularly BFCNs, contributed to learning and memory. Our findings support the prospect of using human stem cell-derived MGE-like progenitors in developing therapies for neurological disorders of learning and memory.
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