Stem cells transdifferentiation

Tao, H. and Ma, D. D. Evidence for transdifferentiation of human bone marrow-derived stem cells recent progress and controversies. Pathology 35 6-13,2003. 

Adult tissue-specific stem cells are present in other self-renewable organs, including the liver, pancreas, skeletal muscle, and skin. The heart, which until very recently was considered a terminally differentiated, postmitotic organ with a finite store of myocytes established at birth, may now be added to this list. It has recently been observed that hematopoietic stem cells (HSCs) can transdifferentiate into car-diomyocytes [33, 34] and that stem cells reside in the heart [35]. These resident cardiac stem cells (CSCs)... 

Resident CSCs were first isolated in murine hearts. Characterization of these cells was based on the expression of the stem cell-related surface antigens c-Kit and Sea-1. In the first study, freshly isolated c-Kit /Lin cells were shown to be clono-genic and to differentiate into myocytes, smooth muscle cells, and endothelial lineage cells [35]. Those cells generated functional myocardium when injected into ischemic areas of the heart. The second study characterized CSCs as Sca-l/c-Kit. When treated in culture with 5-azacytidine, those cells differentiated into a myogenic lineage. Subsequently, intravenous injection of the cells in an ischemia/reperfusion model resulted in infarct healing with cardiomyocyte transdifferentiation... 

The transdifferentiation of HSCs into a mature hematopoietic fate (e.g., endothelium) in the heart is less controversial [148]. In animal models of stem cell therapy in ischemic heart disease, the evidence points toward increased neovascularization (with reduced myocardial ischemia) and consequent improvement in cardiac function [149-151]. Bone marrow stem cells may directly contribute to an increase in contractility or, more likely, may passively limit infarct expansion and remodeling. Unfortunately, the limitations of the present animal models leave this question unanswered. 

With regard to left ventricular function, cardiac stem cell therapy is well tolerated overall. No proar-rhythmic effects have been observed to date with ABMMNC therapy, although other deleterious effects are possible. Early concerns about abnormal transdifferentiation and tumorigenesis have subsided, but the potential for accelerated atherogen-esis remains, given the limited clinical experience... 

Murry CE, Soonpaa MH, Reinecke H, Nakajima H, Nakajima HO, Rubart M, Pasumarthi KB, Virag JI, Bartelmez SH, Poppa V, Bradford G, Dowell JD, Williams DA, Field LJ. Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts. Nature 2004 428 664-668. 

Several sources have reported using stem cells including embryonic stem cells, adult liver progenitors, and transdifferentiated nonhepatic cells in cell-based thera-pies. Hepatocyte lineage in vitro has been reported in murine embryonic stem cells." It is apparent that hematopoietic stem cells can generate hepatocytes directly. This has been shown in rodent models and confirmed in humans by a study of recipients of bone marrow and liver transplants. ... 

Yaon J, Shim WJ, Ro YM, Lim DS. Transdifferentiation of mesenchymal stem cells into cardiomyocytes by direct cell-to-cell contact with neonatal cardiomyocyte but not adult cardiomyocytes. Ann Hematol 2005 84 715-721. 

Adult stem cells are cells found in a number of differentiated tissues that can self-renew and differentiate (with certain limitations) to give rise to the specialized cell types of the tissue. Adult stem cells may also be able to give rise to specialized cell types of a completely different tissue, a phenomenon known as transdifferentiation or plasticity. However, the presence of pluripotent adult stem cells remains a subject of scientific debate. 

Although normal cell development appears to involve a progressive restriction in the developmental potential of cells, recent evidence has suggested that such restriction is not irreversible, and may be altered to reveal novel phenotypic potentials of stem cells, progenitor, and even differentiated cells. These reversible events are explained by a dedifferentiated or transdifferentiated process. Although dedifferentiation and transdifferentiation have the same ultimate end-point, a distinction should be made between the two [58]. In general, dedifferentiation requires the cytokine and sequential markers of an earlier precursor cell that can be identified during the normal pathway of differentiation. However, if... 

Murry, C. E., et al. Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts. Nature 428, 664—668 (2004). 

Song, L. and Tuan, R. S. 2004. Transdifferentiation potential of human mesenchymal stem cells derived from bone marrow. FASEB J, 18, 980-2. 

The extent to which stem cells can actually participate in new blood vessels may be very dependent on the cell type and microenvironment. Very detailed fluorescent cell labeling and confocal imaging of transplanted cells into skeletal muscle revealed that while MSCs could participate in neovascularization, the extent of transdifferentation toward vascular cell types was minimal [88]. Our laboratory has demonstrated that while MSCs could readily transdifferentiate into vascular cells including ECs in vitro, the extent of trandifferentation in vivo in a mouse MI model was not correlated with the extent of new blood vessel formation [49,89]. 

Stem cells are primitive cells, which are present in all organisms and have the ability to divide and give rise to more stem cells, or switch to become more specialized cells in human body like cells in brain, heart, muscle, and kidney [1]. There are two types of stem cell embryonic stem (ES) cell and adult stem cell. ES cells are pluripotent and harvested from inner cell mass of blastocyst and possess the ability to differentiate into all of the specialized embryonic tissues [1], [2]. ES cells also may open the door to the rapidly progressing field of therapeutic cell transplantation [3]. The adult stem cells are multipotent with capacity to differentiate or transdifferentiate into cell types other than their tissue of origin [1]. Adult stem cells and progenitor cells can be found in the adult tissue. Both of these cells act as a repair system for body, replenishing the specialized cells,... 

Recent research has indicated that adult stem cells can differentiate to cells of another lineage, which is referred to as plasticity or transdifferentiation. Plasticity refers to differentiation to cells within the same germ layer, while transdifferentiation designates crossing barriers to another germ layer. For example, bone marrow transplants have demonstrated both plasticity by differentiating into other cells of the mesoderm and transdifferentiation into cells originating in the ectoderm and endoderm. 

Stem and progenitor cells origins, phenotypes, lineage commitments, and transdifferentiations. Anna Rev Cell Dev Biol 17, 387-403 (2001). 

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