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Department of Cell Biology, Neurobiology, and Anatomy and the Cardiovascular Center Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
The Anatomical Record Part A Discoveries in Molecular Cellular and Evolutionary Biology 11/2006; 288(11):1216-24. DOI: 10.1002/ar.a.20388
Source: PubMed


Because pluripotent embryonic stem cells (ESCs) are able to differentiate into any tissue, they are attractive agents for tissue regeneration. Although improvement of cardiac function has been observed after transplantation of pluripotent ESCs, the extent to which these effects reflect ESC-mediated remuscularization, revascularization, or paracrine mechanisms is unknown. Moreover, because ESCs may generate teratomas, the ability to predict the outcome of cellular differentiation, especially when transplanting pluripotent ESCs, is essential; conversely, a requirement to use predifferentiated ESCs would limit their application to highly characterized subsets that are available in limited numbers. In the experiments reported here, we transplanted low numbers of two murine ESC lines, respectively engineered to express a beta-galactosidase gene from either a constitutive (elongation factor) or a cardiac-specific (alpha-myosin heavy chain) promoter, into infarcted mouse myocardium. Although ESC-derived tumors formed within the pericardial space in 21% of injected hearts, lacZ histochemistry revealed that engraftment of ESC was restricted to the ischemic myocardium. Echocardiographic monitoring of ESC-injected hearts that did not form tumors revealed functional improvements by 4 weeks postinfarction, including significant increases in ejection fraction, circumferential fiber shortening velocity, and peak mitral blood flow velocity. These experiments indicate that the infarcted myocardial environment can support engraftment and cardiomyogenic differentiation of pluripotent ESCs, concomitant with partial functional recovery.

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Available from: Zhi-Dong Ge, Oct 08, 2015
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    • "This plasticity is a challenge because we do not understand the myriad of cues capable of directing differentiation. This is particularly problematic with pluripotent stem cells whose ability to generate cells of all embryonic germ layers presents the very real problem of teratoma formation when these cells are used for tissue repair [1], [2]. To circumvent this problem, one method would be to separate the differentiating cells from those that retain pluripotency. "
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    ABSTRACT: The therapeutic potential of stem cells is limited by the non-uniformity of their phenotypic state. Thus it would be advantageous to noninvasively monitor stem cell status. Driven by this challenge, we employed multidimensional multiphoton microscopy to quantify changes in endogenous fluorescence occurring with pluripotent stem cell differentiation. We found that global and cellular-scale fluorescence lifetime of human embryonic stem cells (hESC) and murine embryonic stem cells (mESC) consistently decreased with differentiation. Less consistent were trends in endogenous fluorescence intensity with differentiation, suggesting intensity is more readily impacted by nuances of species and scale of analysis. What emerges is a practical and accessible approach to evaluate, and ultimately enrich, living stem cell populations based on changes in metabolism that could be exploited for both research and clinical applications.
    PLoS ONE 08/2012; 7(8):e43708. DOI:10.1371/journal.pone.0043708 · 3.23 Impact Factor
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    • "Moreover, their unique characteristics related to the differentiation, regeneration, development, remodeling, and replenishment of aged and diseased tissues make them perfect candidates in this area. In a very easy and simple way, stem cells can be conceptually divided into two types: embryonic stem cells (ESCs) – derived from a very early embryo and adult stem cells – found in postnatal tissues, of both the body (bone marrow [BM], adipose tissue, etc) and the umbilical cord (UC).1 "
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    ABSTRACT: During the last decade, due to advances in functionalization chemistry, novel nanobiomaterials with applications in tissue engineering and regenerative medicine have been developed. These novel materials with their unique physical and chemical properties are bioactive hierarchical structures that hold great promise for future development of human tissues. Thus, various nanomaterials are currently being intensively explored in the directed differentiation of stem cells, the design of novel bioactive scaffolds, and new research avenues towards tissue regeneration. This paper illustrates the latest achievements in the applications of nanotechnology in tissue engineering in the field of regenerative medicine.
    International Journal of Nanomedicine 04/2012; 7:2211-25. DOI:10.2147/IJN.S29975 · 4.38 Impact Factor
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    • "Neoplastic progression of differentiated somatic cells used for cell based therapy is a critical problem [4]. However, failure to execute differentiation in a small fraction of cells that could contaminate the donor cells used for transplantation is also critical to PSC tumorigenicity, as the most common tumor type documented after transplantation of differentiated donor cells derived from PSCs are teratomas [3], [12], [13], [14], [15], [16]. In one study using murine induced pluripotent stem (iPS) cells, it was shown that the number of Nanog-positive ECCs that persisted during neurosphere differentiation in vitro correlated with teratoma formation of the transplanted neurospheres in vivo [3]. "
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    ABSTRACT: Pluripotent stem cells (PSCs) hold significant promise in regenerative medicine due to their unlimited capacity for self-renewal and potential to differentiate into every cell type in the body. One major barrier to the use of PSCs is their potential risk for tumor initiation following differentiation and transplantation in vivo. In the current study we sought to evaluate the role of the tumor suppressor Pten in murine PSC neoplastic progression. Using eight functional assays that have previously been used to indicate PSC adaptation or transformation, Pten null embryonic stem cells (ESCs) failed to rate as significant in five of them. Instead, our data demonstrate that the loss of Pten causes the emergence of a small number of aggressive, teratoma-initiating embryonic carcinoma cells (ECCs) during differentiation in vitro, while the remaining 90-95% of differentiated cells are non-tumorigenic. Furthermore, our data show that the mechanism by which Pten null ECCs emerge in vitro and cause tumors in vivo is through increased survival and self-renewal, due to failed repression of the transcription factor Nanog.
    PLoS ONE 01/2011; 6(1):e16478. DOI:10.1371/journal.pone.0016478 · 3.23 Impact Factor
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