Fairchild Paul J
Curr Opin Organ Transplant. 2009 Aug;14(4):321-5. doi: 10.1097/MOT.0b013e32832e9424.
In a seminal paper in 2006, Yamanaka and coworkers reported the reprogramming of terminally differentiated murine cells to a pluripotent state, largely indistinguishable from conventional embryonic stem cells. The introduction of defined transcription factors via retroviral transduction revealed, in principle, how pluripotency, once thought to be lost at an early stage of embryogenesis, could be reawakened in adulthood.
Since these initial findings, induced pluripotency has been reported using human as well as mouse cells and through the introduction of recombinant proteins, thereby avoiding the use of retroviruses for genetic modification. This approach, therefore, harnesses the traditional plasticity of embryonic stem cells as a source of therapeutic cell types and tissues, but without the many ethical issues with which they have become synonymous. The potential for exploiting pluripotency in this way also raises the tantalizing prospect of personalized therapies, spawning a new chapter in the story of regenerative medicine.
Given the promise of induced pluripotency and the disarming ease with which it can be achieved, it is perhaps timely to address the likely effect it will have on the field of transplantation and to ask whether the generation of induced pluripotent stem cells of autologous origin is ever likely to render redundant the need for transplantation tolerance.
2006年,山中伸弥及其同事发表了一篇具有开创性的论文,报道了终末分化的小鼠细胞可被重编程为多能状态,这一状态与传统胚胎干细胞在很大程度上难以区分。通过逆转录病毒转导引入特定转录因子,原则上揭示了一度被认为在胚胎发育早期就已丧失的多能性如何在成年期被重新唤醒。
自这些最初的发现以来,已报道利用人类和小鼠细胞以及通过引入重组蛋白诱导多能性,从而避免使用逆转录病毒进行基因改造。因此,这种方法利用了胚胎干细胞传统的可塑性,将其作为治疗性细胞类型和组织的来源,但避免了与之相关的诸多伦理问题。以这种方式利用多能性的潜力也带来了个性化治疗的诱人前景,为再生医学的故事开启了新的篇章。
鉴于诱导多能性的前景以及实现它的轻松程度,或许是时候探讨它对移植领域可能产生的影响,并询问自体来源的诱导多能干细胞的产生是否可能使移植耐受的需求变得多余。