Transdifferentiation

D Aitken, J Friend, RA Thoft, WR Lee. (1988). An ultrastructural study of rabbit ocular surface transdifferentiation. Invest Ophthalmol Vis Sci 29 224-231. 

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. 

Chen SP, Zhou B, Willis BC, Sandoval AJ, Liebler JM, Kim KJ, Ann DK, Crandall ED, Borok Z (2005) Effects of transdifferentiation and EGF on claudin isoform expression in alveolar epithelial cells. J Appl Physiol 98(1) 322-328... 

Danto SI, Shannon JM, Borok Z, Zabski SM, Crandall ED (1995) Reversible transdifferentiation of alveolar epithelial cells. Am J Respir Cell Mol Biol 12(5) 497-502... 

The current studies were conducted in rodents with I/R ARE, an extensively investigated, albeit imperfect model of the most common and the most treatment-resistant type of clinical AKI. Morigi et al. (Morigi et al, 2004), using rodents with cisplatinum-induced ARE, showed that administration of MSC improved renal function, and MSC appeared to directly contribute to the reconstitution of renal epithelium by transdifferentiation. However, these investigators did not demonstrate that the observed transdifferentiation of MSC is the actual mechanism of renoprotection, and they presented no data regarding the actual numbers of donor cells that undertook the tubular repair. It may be... 

The transdifferentiation of HSCs to myofibroblasts, producing extracellular matrix constituents is characterized by an increased expression of several receptors, including the... 

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... 

CD34 cells contained human X chromosomes only. Thus, human CD34 cells both fused with and transdifferentiated into cardiomyocytes in this mouse model. In addition, human CD34 cells also transdifferentiated into endothelial cells. 

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. 

Yeh ET, Zhang S, Wu HD, Korbling M, Willerson JT, Estrov Z. Transdifferentiation of human peripheral blood CD34 +-enriched cell population into cardio-myocytes, endothelial cells, and smooth muscle cells in vivo. Circulation 2003 108 2070-2073. 

Zhang S, Wang D, Estrov Z, Raj S, Willerson JT, Yeh ET. Both cell fusion and transdifferentiation account for the transformation of human peripheral blood CD34-positive cells into cardiomyocytes in vivo. Circulation 2004 10 3803-3807. 

EMT is a process that occurs during normal development and during tissue homeostasis, which essentially involves a transdifferentiation mechanism allowing epithelial cells to migrate from attached substrata to distal sites within tissues. EMT occurs as... 

Failure of bone marrow cells to transdifferentiate into neural cells in vivo. Science, 291, 1299. 

Mezey, E., Nagy, A., Szalayova, I., Key, S., Bratincsak, A., Baffr, J., Shahar, T. (2003). Comment on "Failure of bone marrow cells to transdifferentiate into neural cells in vivo". Science, 299, 1184. 

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. ... 

De Vriese AS, Tilton RG, Mortier S, Lameire NH. 2006. Myofibroblast transdifferentiation of mesothelial cells is mediated by rage and contributes to peritoneal fibrosis in uraemia. Nephrol Dial Transplant. 

This process of transdifferentiation is preceded by a significant decline in the activity of those enzymes that are recognized as markers of neuroglial specificity. This is the case of the enzyme glutamine synthetase, the marker of astrocytes, which... 

Kodoma, R. and Eguchi, G.(1994) The loss of gap junctional cell-to-cell communication is coupled with dedifferentiation of retinal pigmented epithelial cells in the course of transdifferentiation into the lens. International Journal of Developmental Biology 38... 

M. G. Bachem, D. Meyer, W. Schafer, U. Riess, R. Melchior, K. M. Sell, and A. M. Gressner, The response of rat liver perisinusoidal lipocytes to polypeptide growth regulator changes with their transdifferentiation into myofibroblast-like cells in culture, J. Hepatol. 78 40-52 (1993). 

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. 

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