differentiation - Stem Cells from Differentiated Cells...

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81 April 2004 Volume 4, Issue 2 Stem Cells from Differentiated Cells Panagiotis A. Tsonis Department of Biology, 300 College Park, University of Dayton Dayton, OH 45469–2320 Urodele amphibians, such as salamanders and newts, are largely known for their extraordinary regenerative capabilities. These animals can regenerate amputated limbs, tail, removed retina and lens, heart, spinal cord, brain––virtually anything as long as the animal is left alive (1) . What is truly striking is that regeneration occurs in adult amphibians and involves the usage of already existing terminally differentiated cells, rather than undifferentiated stem cells. For example, after limb amputation, the tissues in the stump, such as muscle and cartilage, lose their tissue characteris- tics that distinguish them. This “dedifferentiation” process leads to the formation of the blastema (2, 3) . Cells within the blastema are undifferentiated, but soon after a period of proliferation, these cells redifferentiate to build a faithful replica of the lost part of the limb (Figure 1). Likewise, when the eye lens is removed from uro- deles, the pigment epithelial cells (PECs) of the dorsal iris dedif- ferentiate, thereby losing their characteristic pigmentation and producing a lens vesicle, which, in turn, differentiates to lens epi- thelium at the anterior and to lens fibers at the posterior (Figure 1). Even isolated single PECs can transdifferentiate to lens in vitro (4) . From these two examples, we can firmly conclude that regen- eration occurs via “transdifferentiation,” because one terminally differentiated cell has been reprogrammed to become another. This reprogramming has virtually no parallel in other normal dif- ferentiation processes. In the past few years, however, many studies have shown that stem cells––cells that are reserved and used for repair––might have greater potential for regeneration than originally thought. Stem cells can be local (i.e., located in the brain and involved in nervous tissue repair), or non-local (i.e., hematopoieitic and involved in repair of several different tissues, such as liver, ner- vous, or cardiac) (5–8) . Despite some spectacular results, a direct role for non-local stem cells in repair has been disputed, mainly because stem cells can fuse with the cells at the site of repair (9) . One should keep in mind that, unlike the strategy used by uro- deles, mammalian stem cells do not undergo dedifferentiation, but rather pre-exist as multipotent cells. Therefore, this repair strategy is not the same as the one used in urodeles. It has been hypothesized, however, that some similarities
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This note was uploaded on 04/26/2010 for the course SCI 35254 taught by Professor George during the Spring '10 term at Aarhus Universitet.

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differentiation - Stem Cells from Differentiated Cells...

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