Until recently a paucity of understanding

Until recently, a paucity of understanding about the cellular homeostasis of most adult solid tissues has been a major factor limiting the expansion to other areas of medicine of the early breakthroughs in adult stem cell research and therapy, such as those applied to the blood and bone marrow diseases. Early in the last decade the prevalent view was that, although tissues like the bone marrow, intestinal epithelium and skin exhibit a robust self-renewal capacity based on the presence of adult (also called “tissue-specific”) stem buy Cilengitide (Mercier et al., 2011; Simons et al., 2011; Fuchs, 2009), they were an exception. The established paradigm was that the majority of the remaining solid tissues either renewed very slowly (such as the muscle and the endothelial lining of the vascular system), with renewal being physiologically irrelevant, or not at all. It was firmly believed that starting shortly after birth many tissues did not harbour functional regenerating (stem) cells. A logical consequence of the above paradigm was the belief that for most organs the number and function of their parenchymal cells was in a downward spiral starting in late infancy and continued until death. With the exception of the three main self-renewing tissues mentioned above, it necessarily followed that all therapeutic approaches to disease processes caused by a deficit in the number of functional parenchymal cells could be only directed toward improving and/or preserving the performance of the functional cells remaining in the tissue. Thus, to return the tissue or organ to the status quo ante required the transplantation of either identical cells from another individual or transplantation of a cell type capable of differentiating into the cells whose shortage needed to be covered. Because the cells needed for the second option did not exist for the majority of tissues, heterologous/allogeneic organ and cell transplantation became the only possible avenues. In fact, despite the multiple drawbacks of heterologous cell/organ transplantation, its practice has become the cutting edge for several medical specialties (Badylak et al., 2012). However, the extreme shortage of donors, high costs, and the severe side effects of immunosuppression have limited this therapy to a small fraction of candidates in need of treatment. Thus, the positive reception and high expectations that received the successful derivation of multipotent human embryonic stem cells (hESCs) (Evans et al., 1981; Thomson et al., 1998; Murry, 2008) with the capacity to differentiate into most, if not all, known cell types promised an unlimited supply of donor parts. When the euphoria caused by this development started to dim, because of the ethical and immunological challenges posed by the use of hESCs, came the breakthrough which permitted the conversion of different adult somatic cells, such as fibroblasts, into multipotent cells called induced pluripotent stem (iPS) cells by introduction of a very limited number of genes (now known to be responsible for the multipotent state of stem cells) (Takahashi et al., 2006; Takahashi et al., 2007) or their products. With the development of iPS cells, it became possible to produce different types of parenchymal cells starting with an abundant and easy to obtain cell type from the same patient to be treated. Once converted into the parenchymal type needed, these could be potentially used for autologous cell therapy (Yamanaka, 2007). Although the potential of the iPS cells as therapeutic agents remains high, it is already clear that many hurdles need to be cleared before they can reach clinical application (Robinton et al., 2012). The recent protocols to convert somatic cells directly into some types of parenchymal cells without apparently going through the multipotent stage by introducing tissue-specific transcriptional factors (Qian et al., 2012; Song et al., 2012; Jayawardena et al., 2012) might be too recent to evaluate their clinical potential.