Wataya Takafumi, Muguruma Keiko, Sasai Yoshiki
Organogenesis and Neurogenesis Group, Center for Developmental Biology, RIKEN, 2-2-3 Minatojima-minamimachi, Kobe, Hyogo 650-0047, Japan.
Brain Nerve. 2008 Oct;60(10):1165-72.
Recovery of lost brain function is an important issue in medical studies because neurons of the central nervous system (CNS) have poor potential for regeneration. Since few CNS diseases can be treated completely by medicines, regenerative therapy by using stem cells should be studied as a new type of therapeutic intervention. The efficacy of cell replacement therapy in Parkinson's disease has been well investigated. Several studies on fetal tissue transplantation have revealed that quantity and purity of transplanted cells are necessary for recovery of symptoms. SFEB (Serum-free floating culture of embryoid body-like aggregates) method is capable of inducing multi-potential CNS progenitors that can be steered to differentiate into region-specific tissues. On the basis of the existing knowledge of embryology, we have succeeded in the generating of various types of neurons such as telencephalic, cerebeller (Purkinje and granule cells), retinal (photoreceptor cells) and hypothalamic neurons. Application of this culture method to human ES (hES) cells is necessary for clinical purpose: however, poor survival of hES cells in SFEB culture might limit the possibility of using these cells for future medical applications. We found that a selective Rho-associated kinase (ROCK) inhibitor, Y-27632, markedly diminished the dissociation-induced apoptosis of hES cells and enabled the cells to form aggregates in SFEB culture. For both mouse and human ES cells, SFEB culture is a favorable method that can generate large amounts of region-specific neurons. However, stem cell-based therapy continues to face several obstacles. It is important that researchers in the basic sciences and clinical medicine should discuss these problems together to overcome both scientific and ethical issues related to stem cells.
恢复丧失的脑功能是医学研究中的一个重要问题，因为中枢神经系统（CNS）的神经元再生潜力较差。由于很少有中枢神经系统疾病能够通过药物完全治愈，因此应研究使用干细胞的再生疗法作为一种新型的治疗干预手段。细胞替代疗法在帕金森病中的疗效已得到充分研究。多项关于胎儿组织移植的研究表明，移植细胞的数量和纯度对于症状的恢复是必要的。SFEB（无血清悬浮培养类胚体样聚集体）方法能够诱导多能中枢神经系统祖细胞，这些祖细胞可以被引导分化为区域特异性组织。基于现有的胚胎学知识，我们已经成功地生成了各种类型的神经元，如端脑、小脑（浦肯野细胞和颗粒细胞）、视网膜（光感受器细胞）和下丘脑神经元。将这种培养方法应用于人类胚胎干细胞（hES细胞）对于临床应用是必要的；然而，hES细胞在SFEB培养中的低存活率可能会限制将这些细胞用于未来医学应用的可能性。我们发现，一种选择性的Rho相关激酶（ROCK）抑制剂Y-27632能显著减少hES细胞解离诱导的凋亡，并使细胞能够在SFEB培养中形成聚集体。对于小鼠和人类胚胎干细胞来说，SFEB培养都是一种能够产生大量区域特异性神经元的良好方法。然而，基于干细胞的治疗仍然面临几个障碍。基础科学和临床医学领域的研究人员共同讨论这些问题以克服与干细胞相关的科学和伦理问题非常重要。
