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首页 » 干细胞&iPS » Science & Cell子刊:丁胜突破性成果!利用特殊药物将皮肤细胞成功转化为心脏和大脑细胞

Science & Cell子刊:丁胜突破性成果!利用特殊药物将皮肤细胞成功转化为心脏和大脑细胞

来源:生物谷 2016-05-02 23:18

图片来源:medicalxpress.com

2016年5月2日 讯 /生物谷BIOON/ --近日,来自格莱斯顿研究所(Gladstone Institutes)的科学家们利用一种组合性化学物成功将皮肤细胞转化成为心脏细胞和大脑细胞,此前对细胞重编程的工作都需要向细胞中添加额外的基因;近日刊登在国际杂志ScienceCell Stem Cell上的两篇研究论文中,研究人员就利用混合的化学物逐渐诱导皮肤细胞改变成为器官特异性的干细胞样细胞,最终发育成为心脏和大脑细胞,而这项研究发现或许就提供了一种有效可靠的方法来对细胞进行重编程并且避免相应问题的发生。

研究者Ding表示,这种方法或可帮助我们为患者制造新型细胞来治疗疾病,我们希望有一天可以利用本文中的方法来治疗诸如心脏病和帕金森等人类疾病。

刊登在Science上的研究论文中,研究人员利用9种化合物的混合制剂将人类皮肤细胞进行改变使其成为跳动的心脏细胞,经过反复试验,研究者通过将细胞改变成为类似多潜能干细胞的状态,最终发现了开启转化过程的最佳化合物组合模式,随后就可以在特殊的器官中诱导皮肤细胞产生多种不同类型的细胞。

利用上述方法研究者就可以制造出97%的具有特征、完全发育健康的心脏细胞,而且这些心脏细胞还会对激素类产生合适的反应,其类似于心肌细胞,而且当这些细胞被植入小鼠的心脏后,其就会在器官中发育成为看起来非常健康的心肌细胞。研究者治疗心力衰竭的最终目标就是开发一种强大可靠的方法来制造新型的心肌细胞,而对患者自身的细胞进行重编程或许就为治疗疾病提供了可靠的方法。

另一篇刊登于国际杂志Cell Stem Cell上的研究论文中,科学家们利用上述类似方法通过小鼠的皮肤细胞制造出了神经干细胞。这些混合的化合物中包含了9种分子,其中有些在上述的研究中已经使用过了,经过10天时间这些化合物就可以改变细胞的“身份”,直到所有的皮肤细胞的基因都被关闭同时神经干细胞的所有基因被开启;当将新生的神经干细胞移植入小鼠机体中后,这些干细胞就会自发发育成为三种基本类型的脑细胞:神经元、寡突细胞和星形细胞,这些神经干细胞同时还可以进行自我复制,从而帮助治疗大脑损伤或神经变性疾病。

最后Yadong Huang博士说道,随着试验安全性的改善,我们相信未来终将有一天这些新生的神经干细胞可以被用作细胞替代疗法来治疗诸如帕金森疾病和阿尔兹海默氏症等神经变性疾病;未来我们就可以利用药物混合制剂来治疗多种疾病的患者,比如大脑和脊髓损伤等疾病。(生物谷Bioon.com)

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Conversion of human fibroblasts into functional cardiomyocytes by small molecules

Nan Cao1,2, Yu Huang1, Jiashun Zheng4,5, C. Ian Spencer1, Yu Zhang1,2, Ji-Dong Fu6, Baoming Nie1,2, Min Xie1,2, Mingliang Zhang1,2, Haixia Wang1,2, Tianhua Ma1,2, Tao Xu1,2, Guilai Shi1,2, Deepak Srivastava1,3,4,*, Sheng Ding1,2,*,†

Reprogramming somatic fibroblasts into alternative lineages would provide a promising source of cells for regenerative therapy. However, transdifferentiating human cells to specific homogeneous, functional cell types is challenging. Here we show that cardiomyocyte-like cells can be generated by treating human fibroblasts with a combination of nine compounds (9C). The chemically induced cardiomyocyte-like cells (ciCMs) uniformly contracted and resembled human cardiomyocytes in their transcriptome, epigenetic, and electrophysiological properties. 9C treatment of human fibroblasts resulted in a more open-chromatin conformation at key heart developmental genes, enabling their promoters/enhancers to bind effectors of major cardiogenic signals. When transplanted into infarcted mouse hearts, 9C-treated fibroblasts were efficiently converted to ciCMs. This pharmacological approach for lineage-specific reprogramming may have many important therapeutic implications after further optimization to generate mature cardiac cells.

Pharmacological Reprogramming of Fibroblasts into Neural Stem Cells by Signaling-Directed Transcriptional Activation

Mingliang Zhang, Yuan-Hung Lin, Yujiao Jennifer Sun, Saiyong Zhu10, Jiashun Zheng, Kai Liu, Nan Cao, Ke Li, Yadong Huang, Sheng Ding

Cellular reprogramming using chemically defined conditions, without genetic manipulation, is a promising approach for generating clinically relevant cell types for regenerative medicine and drug discovery. However, small-molecule approaches for inducing lineage-specific stem cells from somatic cells across lineage boundaries have been challenging. Here, we report highly efficient reprogramming of mouse fibroblasts into induced neural stem cell-like cells (ciNSLCs) using a cocktail of nine components (M9). The resulting ciNSLCs closely resemble primary neural stem cells molecularly and functionally. Transcriptome analysis revealed that M9 induces a gradual and specific conversion of fibroblasts toward a neural fate. During reprogramming specific transcription factors such as Elk1 and Gli2 that are downstream of M9-induced signaling pathways bind and activate endogenous master neural genes to specify neural identity. Our study provides an effective chemical approach for generating neural stem cells from mouse fibroblasts and reveals mechanistic insights into underlying reprogramming processes.

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