Department of Pediatrics/Human Development, College of Human Medicine, Michigan State University, East Lansing, Michigan.
Anat Rec (Hoboken). 2014 Jan;297(1):161-73. doi: 10.1002/ar.22793. Epub 2013 Dec 2.
This article as designed to examine whether the "stoichiometric" or "elite models" of the origin of the "induced pluripotent stem" (iPS) cells fits some experiment facts from the developmental biology of adult stem cells and from the field of cancer research. In brief, since the evidence presented to support the stoichiometric model failed to recognize the factual existence of adult organ specific stem cells, the model has not been rigorously tested. In addition, the demonstration of a subset of cells (MUSE cells) in normal primary in vitro cultures of human fibroblasts (the usual source of iPS cells) seems to be the origin of the iPS cells. Moreover, from the field of carcinogenesis, the "stem cell" versus "de-differentiation" or "reprogramming" hypotheses were examined. Again, using the role of glycolysis, known to be associated with the Warburg effect in cancer cells, a list of experiments showing that (a) normal stem cells, which have few mitochondria, metabolize via glycolysis; (b) the stem cells are targets for "initiation" or "immortalization" or the blockage of differentiation and apoptosis of the stem cells by "immortalizing viruses"; (c) Lactate dehydrogenase A (LDHA), when expressed, is associated with glycolysis and therefore, must be expressed in normal adult stem cells, as well as in cancer cells; and (d) p53, depleted or rendered dysfunctional by SV40 Large T antigen, is associated with the reduction of mitochondrial function and mass and is associated with the Warburg effect. Together, these observations from the iPS and "cancer stem cell" fields support the idea that both iPS cells and cancer stem cell are derived from adult organ-specific stem cells that do not restore or switch their metabolism of glucose from oxidative metabolism to glycolysis but, rather, in both cases, the adult stem cell, which metabolizes by glycolysis, is prevented from differentiation or from metabolizing by oxidative phosphorylation.
本文旨在探讨“诱导多能干细胞”（iPS 细胞）起源的“化学计量”或“精英模型”是否符合一些来自成人干细胞发育生物学和癌症研究领域的实验事实。简而言之，由于支持化学计量模型的证据未能认识到成人器官特异性干细胞的实际存在，因此该模型尚未得到严格测试。此外，在人成纤维细胞（通常是 iPS 细胞的来源）的正常原代体外培养中，发现了一组细胞（MUSE 细胞），这些细胞似乎是 iPS 细胞的起源。此外，从致癌作用的角度来看，还检验了“干细胞”与“去分化”或“重编程”假说。同样，利用与癌细胞中的沃伯格效应相关的糖酵解作用的作用，列出了一系列实验，这些实验表明：（a）正常干细胞具有很少的线粒体，通过糖酵解代谢；（b）干细胞是“起始”或“永生化”或阻止干细胞分化和凋亡的靶标，这种作用是由“永生化病毒”介导的；（c）当表达乳酸脱氢酶 A（LDHA）时，它与糖酵解相关，因此，必须在正常的成人干细胞中表达，也必须在癌细胞中表达；（d）p53 被 SV40 大 T 抗原耗尽或功能失调，与线粒体功能和质量的减少相关，并且与沃伯格效应相关。总的来说，这些来自 iPS 和“癌症干细胞”领域的观察结果支持这样一种观点，即 iPS 细胞和癌症干细胞都来源于成人器官特异性干细胞，这些干细胞不会将其葡萄糖代谢从氧化代谢恢复或转变为糖酵解，但在这两种情况下，通过糖酵解代谢的成体干细胞会被阻止分化或被阻止通过氧化磷酸化代谢。
