Heng B C, Liu H, Cao T
Stem Cell Laboratory, Faculty of Dentistry, National University of Singapore, 5 Lower Kent Ridge Road, 119074 Singapore.
Clin Exp Med. 2005 May;5(1):37-9. doi: 10.1007/s10238-005-0063-6.
In recent years, much interest has been generated over the potential of human embryonic stem cells in transplantation medicine. The ground-breaking study of Fraidenraich and colleagues conclusively demonstrated that rescue of lethal cardiac defects in Id knockout mutant mouse embryos was not due to transplanted embryonic stem cells giving rise to functional new tissues within the defective embryonic heart. Instead, there is indirect evidence that the observed therapeutic effect was due to various secreted factors emanating from the transplanted cells. This therefore introduces the exciting prospect of utilizing human embryonic stem cells as "catalysts" to promote biological repair and regeneration in transplantation therapy. Nevertheless, the immunological barrier against allogenic transplantation, as well as the teratogenic potential of human embryonic stem cells poses major technical challenges. A possible strategy to overcome the immunological barrier may be to impose a temporary regimen of immunosuppressive drugs followed by their gradual withdrawal, once adequate tissue regeneration has been achieved. Other more novel alternatives include the use of microencapsulation to block interaction with the transplant recipient's immune system, and co-transplantation with bone marrow-derived mesenchymal stem cells, which have been demonstrated to possess immuno-suppressive properties. The teratogenic potential of human embryonic stem cells could possibly be alleviated by directing the differentiation of these cells to specific lineages prior to transplantation, or through mitotic inactivation. Co-transplantation with autologous adult stem cells may represent a novel strategy to further enhance the "catalytic" effects of human embryonic stem cells. The various factors secreted by human embryonic stem cells could then have a concentrated localized effect on relatively large numbers of co-transplanted autologous adult stem cells, which may in turn lead to enhanced repair and regeneration of the damaged tissue or organ. This new therapeutic strategy needs to rigorously investigated, in view of its potentially important clinical applications.
近年来，人类胚胎干细胞在移植医学中的潜力引发了广泛关注。弗赖登赖希及其同事的开创性研究确凿地表明，Id基因敲除突变小鼠胚胎中致命心脏缺陷的挽救并非源于移植的胚胎干细胞在有缺陷的胚胎心脏内形成功能性新组织。相反，有间接证据表明，观察到的治疗效果是由于移植细胞分泌的各种因子所致。因此，这引入了一个令人兴奋的前景，即利用人类胚胎干细胞作为“催化剂”来促进移植治疗中的生物修复和再生。然而，同种异体移植的免疫屏障以及人类胚胎干细胞的致畸潜力构成了重大技术挑战。克服免疫屏障的一种可能策略可能是采用短期免疫抑制药物方案，一旦实现充分的组织再生，便逐渐停药。其他更新颖的替代方法包括使用微囊化来阻断与移植受体免疫系统的相互作用，以及与已证明具有免疫抑制特性的骨髓间充质干细胞共移植。人类胚胎干细胞的致畸潜力可能通过在移植前将这些细胞定向分化为特定谱系或通过有丝分裂失活来减轻。与自体成体干细胞共移植可能是进一步增强人类胚胎干细胞“催化”作用的一种新策略。然后，人类胚胎干细胞分泌的各种因子可能会对相对大量的共移植自体成体干细胞产生集中局部效应，这反过来可能会增强受损组织或器官的修复和再生。鉴于其潜在的重要临床应用，这种新的治疗策略需要进行严格研究。
