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Human Liver Stem Cells:
Published in Gianfranco Alpini, Domenico Alvaro, Marco Marzioni, Gene LeSage, Nicholas LaRusso, The Pathophysiology of Biliary Epithelia, 2020
However, as indicated with the experimental rodent literature, there is currendy considerable debate concerning the extent to which this process occurs clinically or experimentally. Indeed as indicated, many investigators now believe the number of cells which do undergo the transition from bone marrow stem cells to hepatic, neural or other tissues43,44,54,55 or the other direction i.e., neural to blood56 may in fact be relatively small and repopulation slow. Therefore physiologically in vivo they may well be relatively rare events and there is doubt that the phenomena, although clearly demonstrable in vivo, play any significant role in the response of the human liver to tissue injury. Nevertheless, the principles of transdifferentiation are now established and may well prove of clinical importance subsequendy.
Current developments in human stem cell research and clinical translation
Published in Christine Hauskeller, Arne Manzeschke, Anja Pichl, The Matrix of Stem Cell Research, 2019
Stephanie Sontag, Martin Zenke
The existence of such factors was further supported by the discovery of so-called master transcription factors regulating cell identity. In 1987, Schneuwly et al. attracted attention when they showed that the overexpression of the transcription factor Antennapedia at a specific larval stage in Drosophila melanogaster caused the formation of a second pair of legs instead of antennae (Schneuwly et al., 1987). In the same year, Weintraub and colleagues overexpressed the muscle-specific transcription factor MyoD in a fibroblast cell line and demonstrated conversion to muscle cells (Davis et al., 1987). Several years later, expression of the red cell transcription factor Gata1 converted monocyte/macrophage cells into erythroid cells (Kulessa et al., 1995). Conversely, the introduction and expression of transcription factor Pu.1 switched erythroid-megakaryocytic into monocytic cells (Nerlov and Graf, 1998). These direct fate conversions of somatic cells, a process known as transdifferentiation, supported the notion that cell differentiation and specialization are dependent on gene expression and thus can be modulated. Yet these findings were still met with caution as they were obtained with cell lines, which are generally more plastic than primary cells (Graf and Enver, 2009). These objections were dismissed when Thomas Graf and colleagues demonstrated transdifferentiation of primary mouse B cells into macrophages with Cebpα overexpression (Xie et al., 2004).
Tissue engineering and regeneration
Published in Professor Sir Norman Williams, Professor P. Ronan O’Connell, Professor Andrew W. McCaskie, Bailey & Love's Short Practice of Surgery, 2018
Professor Sir Norman Williams, Professor P. Ronan O’Connell, Professor Andrew W. McCaskie
The major safety concerns of cell-based therapy and tissue engineering are listed in Table4.5. One of the most serious concerns is that of tumour formation and malignant transformation. The risk of tumour formation varies according to the cell type used, the genetic modification strategy used to transform the stem cells, the site of transplantation and whether the cells are autologous or allogeneic. The direct risk of tumour formation by the transplanted cells relates specifically to ESCs and iPSCs and there appears to be little risk with SSCs. The ability of stem cells to form teratomas is one of the hallmarks of pluripotency, and the risk of this happening following stem cell therapy may be reduced by ensuring that only cells that have been fully differentiated in vitro and not those that are still pluripotent are used for therapy. The risk of malignancy may also be reduced by the choice of in vitro strategy used to differentiate stem cells prior to use: use of viral vectors that do not integrate into the genome or of non-viral approaches to differentiation reduces the risk of malignant transformation. There is also interest in developing techniques for directly reprogramming somatic cells to adopt the function of a different cell type without having to make them first revert back to the pluripotent state - so-called transdifferentiation.
Experimental drugs for the prevention or treatment of sensorineural hearing loss
Published in Expert Opinion on Investigational Drugs, 2023
Judith S Kempfle, David H. Jung
Active lateral inhibition determines the fate of hair cells or supporting cells from common progenitors during development, and active Notch signaling in mature supporting cells prohibits them from transdifferentiating into hair cells [98]. Signal transduction of the transmembrane protein Notch is induced by cleavage of its intracellular domain via the enzyme γ-secretase. Inhibition of γ-secretases by small molecule drugs thereby renders the Notch pathway inactive and enables hair cell differentiation from surrounding supporting cells [99]. More than 100 different γ-secretase inhibitors of two different subtypes have been synthesized, originally for applications in the central nervous system (CNS) [100]. Previous drug screens initially identified LY411575 as one of the most effective inhibitors in the inner ear [99,101], but since then, additional γ-secretase inhibitors with inner ear activity have been discovered, some of which are currently being tested in clinical trials for SNHL (Table 2). There is ongoing debate about the utility of a transdifferentiation approach, which in principle would deplete the supporting cell pool, thereby potentially removing necessary trophic support for hair cells [95].
A New Procedure in Bone Engineering Using Induced Adipose Tissue
Published in Journal of Investigative Surgery, 2021
Randa Alfotawi, Mona Elsafadi, Manikandan Muthurangan, Abdul-Aziz Siyal, Musaad Alfayez, Amer A. Mahmmod
One of the proposed approaches is transdifferentiation (better-termed interconversion), which is when one cell type differentiates into another cell type of the same germ lineage through genetic reprograming. The molecular mechanisms regulating the transdifferentiation or interconversion of pre-committed human mesenchymal stem cells (hMSCs) to a given mesenchymal cell lineage in response to inductive extracellular cues are poorly understood,4 but there is strong evidence that human adipose-derived stem cells (ADCs) can be used successfully in bone bioengineering because ADCs are multipotent stem cells that are similar to bone marrow-derived stem cells.9 Similarly, Strem and Hedrick10 investigated the ability of ADCs to bioengineer calvarial bone defects in mice using a novel osteoconductive apatite-coated polylactic-co-glycolic acid scaffold for cell delivery.10
Potential of ovine Wharton jelly derived mesenchymal stem cells to transdifferentiate into neuronal phenotype for application in neuroregenerative therapy
Published in International Journal of Neuroscience, 2020
Lija Satheesan, Eswari Soundian, Vijayarani Kumanan, Kumanan Kathaperumal
Transdifferentiation of stem cells is an unique aspect allowing these cells to regenerate tissues involving other cell types and the MSCs are readily differentiated into NSCs [5]. Nestin expression is a necessary step for neuronal differentiation of MSCs, whereas β III tubulin, is required for axon growth and GFAP helps in maintaining the mechanical strength of astrocyte. In the present study, when WJMSCs cultured in NCM, these cells started to express NSC markers Nestin, β III tubulin and GFAP, indicative of transdifferentiation to NSCs. The expression gradually increased during the course of differentiation. Earlier studies have reported the expression of Nestin, GFAP from low [19] to up regulated [21] after neuronal induction. This variable level of expression might be due to certain inhibitory action of the added serum in the culture medium [22]. Immunocytochemical localization of neuronal markers indicated that these cells were reactive to differentiation medium as they began to express these markers. It was reported that the WJ MSCs were positive for GFAP and it was strongly expressed in WJMSCs when cultured in media conditioned by primary rat brain neurons [10]. Serial passage significantly increased the neural differentiation capability of WJMSCs and the expression of Nestin and βIII tubulin in induced cells [21]. Apart from these markers, the neuronal differentiated BM derived MSCs express other neuronal markers, Flk and Nef [12].