[Human pluripotent stem cell and neural differentiation].
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.
Wataya
Takafumi
T
Organogenesis and Neurogenesis Group, Center for Developmental Biology, RIKEN, 2-2-3 Minatojima-minamimachi, Kobe, Hyogo 650-0047, Japan.
Muguruma
Keiko
K
Sasai
Yoshiki
Y
D000577:Amides / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002449:Cell Aggregation / Q000187:drug effects; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D064987:Cell- and Tissue-Based Therapy; D002490:Central Nervous System / Q000166:cytology*; D004298:Dopamine / Q000502:physiology; D053595:Embryonic Stem Cells / Q000166:cytology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D051379:Mice; D010300:Parkinson Disease / Q000628:therapy; D039904:Pluripotent Stem Cells / Q000166:cytology; D011725:Pyridines / Q000494:pharmacology; D044968:Regenerative Medicine; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors
D000577:Amides; D004791:Enzyme Inhibitors; D011725:Pyridines; C108830:Y 27632; D054460:rho-Associated Kinases; D004298:Dopamine