Laboratorio de Neurociencias, Universidad de los Andes, Las Condes, Santiago, Chile.
Curr Stem Cell Res Ther. 2012 May;7(3):191-6. doi: 10.2174/157488812799859865.
A lot of effort has been developed to bypass the use of embryonic stem cells (ES) in human therapies, because of several concerns and ethical issues. Some unsolved problems of using stem cells for human therapies, excluding the human embryonic origin, are: how to regulate cell plasticity and proliferation, immunological compatibility, potential adverse side-effects when stem cells are systemically administrated, and the in vivo signals to rule out a specific cell fate after transplantation. Currently, it is known that almost all tissues of an adult organism have somatic stem cells (SSC). Whereas ES are primary involved in the genesis of new tissues and organs, SSC are involved in regeneration processes, immuno-regulatory and homeostasis mechanisms. Although the differentiating potential of ES is higher than SSC, several studies suggest that some types of SSC, such as mesenchymal stem cells (MSC), can be induced epigenetically to differentiate into tissue-specific cells of different lineages. This unexpected pluripotency and the variety of sources that they come from, can make MSC-like cells suitable for the treatment of diverse pathologies and injuries. New hopes for cell therapy came from somatic/mature cells and the discovery that could be reprogrammed to a pluripotent stage similar to ES, thus generating induced pluripotent stem cells (iPS). For this, it is necessary to overexpress four main reprogramming factors, Sox2, Oct4, Klf4 and c-Myc. The aim of this review is to analyze the potential and requirements of cellular based tools in human therapy strategies, focusing on the advantage of using MSC over iPS.
为了避免在人类疗法中使用胚胎干细胞 (ES)，人们付出了大量努力，因为存在一些担忧和伦理问题。在将干细胞用于人类疗法时，除了人类胚胎的起源之外，还有一些尚未解决的问题：如何调节细胞的可塑性和增殖、免疫相容性、当干细胞被系统性给药时的潜在不良副作用，以及在移植后排除特定细胞命运的体内信号。目前，人们已经知道，成年生物体的几乎所有组织都有体干细胞 (SSC)。虽然 ES 主要参与新组织和器官的发生，但 SSC 则参与再生过程、免疫调节和内稳态机制。尽管 ES 的分化潜力高于 SSC，但有几项研究表明，某些类型的 SSC，如间充质干细胞 (MSC)，可以通过表观遗传诱导分化为不同谱系的组织特异性细胞。这种出乎意料的多能性以及它们来自的多种来源，可以使 MSC 样细胞适合治疗各种病理和损伤。体细胞/成熟细胞的新希望以及发现它们可以被重新编程为类似于 ES 的多能阶段，从而产生诱导多能干细胞 (iPS)。为此，有必要过表达四个主要的重编程因子，即 Sox2、Oct4、Klf4 和 c-Myc。本文的目的是分析基于细胞的工具在人类治疗策略中的潜力和要求，重点关注使用 MSC 而不是 iPS 的优势。
