Recombinant DNA Technology and Gene Therapy Using Viruses
Patricia G. Melloy in Viruses and Society, 2023
As mentioned in the introduction, induced pluripotent stem cells (iPSCs) are a type of stem cell made by reprogramming adult cells to behave like stem cells. Early work on iPSCs involved using a retroviral-based vector to express a set of genes that turn the clock back on the adult cell nucleus, making it behave like a stem cell present back in early development of the organism. (Alberts et al. 2019; Clarke and Frampton 2020; Kurreck and Stein 2016). Researchers are also working to use adenoviral-based vectors to make iPSCs as well (Stadtfeld et al. 2008). Stem cells are important for regenerative medicine due to their potential to form many cell types of the body, not just one specialized kind. The goal of regenerative medicine is to replace tissues that are affected by disease or worn out with age. Future research will involve further fine-tuning of the iPSC approach to see if these cells can be effectively used to treat patients. Beyond making pluripotent stem cells themselves, researchers are also developing adenoviral vectors to express certain growth factors needed in the tissue specialization process, such as to make bone, to make particular tissues for regenerative purposes (Lee et al. 2017).
Stem cell biology
Christine Hauskeller, Arne Manzeschke, Anja Pichl in The Matrix of Stem Cell Research, 2019
Waddington’s landscape dodges the question, putting the cell lineage tree on a ‘tilt’, which amounts to assuming a force of development as ineluctable as gravity. But we have learned, in part from stem cell biology, that cell development is in fact reversible, and much more plastic and malleable than traditional views of the process would suggest. Cell reprogramming is a method of producing stem cells (induced pluripotent stem cells) from more differentiated cells, effectively reversing normal development (Takahashi and Yamanaka, 2006). This experimental discovery contradicts any strict principle of development as irreversible and internally directed, undermining the notion of a fixed ‘program for development’ (Brandt, 2012). The stem cell concept and its experimental applications present us with fundamental questions about the nature of development.
Tissue engineering and regeneration
Professor Sir Norman Williams, Professor P. Ronan O’Connell, Professor Andrew W. McCaskie in Bailey & Love's Short Practice of Surgery, 2018
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.
Macrophages morphology and cytokine reeducation by ex situ copper thiol complexes
Published in Immunopharmacology and Immunotoxicology, 2023
Jorge Xool-Tamayo, Víctor Ermilo Arana-Argaez, Fabiola Villa-de la Torre, Ivan Chan-Zapata, Rossana F. Vargas-Coronado, Juan V. Cauich-Rodríguez
Currently, the reprogramming of cell biology is an alternative to therapeutic treatments. In this research, we report that all copper thiol complexes had the capability to reeducate M1 to M2 as morphoexpression. The thin elongate M2 morphology was observed between 400 and 800 µM while a high secretion of M2 marker (IL-10) was registered between 200 and 400 µM. In general, the copper thiol cysteine reduced the pro-inflammatory cytokines markers M1 (IL-1β, IL-6) while increasing the expression of M2 (IL-4, IL-10). This study suggests that copper thiol cysteine functions in tissue repair and that they can be used in different biomaterials as fillers. Furthermore, copper thiol penicillamine produces an important amount of M2 (IL-10) marker but has a high effect on pro-inflammatory M1 markers (IL-1β, IL-6). These results suggest a behavior of the copper penicillamine complex as a protective cell (antimicrobial or anticancer).
Stem cell therapy for salivary gland regeneration after radiation injury
Published in Expert Opinion on Biological Therapy, 2023
Akshaya Upadhyay, Simon D Tran
Reprogramming of somatic cells became a reality with induced pluripotent stem cells (established by introducing four factors: Sox2, Oct3/4, c-Myc, and Klf4 in somatic cells). This has inspired researchers to enhance and modify somatic cells for therapeutics. Sumita et al. recently initiated a clinical trial to treat radiation-induced xerostomia using effective-mononuclear cells (E-MNCs) by amplifying peripheral blood mononuclear cells’ anti-inflammatory and vasculogenic properties by expanding these cells in vitro with specific growth factors [26]. Another work with somatic cells worth mentioning here is using mouse embryonic fibroblasts for forming SG organoids. First, the epithelial transition of the fibroblasts was carried out, followed by SG-specific epithelial initiation, which resulted in the successful formation of SG-like organoids [5].
Functional role of ascorbic acid in the central nervous system: a focus on neurogenic and synaptogenic processes
Published in Nutritional Neuroscience, 2022
Morgana Moretti, Ana Lúcia S. Rodrigues
Embryonic stem cells are pluripotent cells isolated from the inner cell mass of an early-stage blastocyst [25]. Embryonic stem cells self-renew by dividing and can differentiate into specialized cells, including neurons, oligodendrocytes, and astrocytes [26]. Induced pluripotent stem cells (iPSCs) are pluripotent stem cells generated from adult cells by reprogramming. iPSCs have the same properties as embryonic stem cells, and therefore self-renew and can differentiate into all cell types [27]. It was reported that ascorbic acid improved the speed and efficiency of the generation of mouse and human iPSCs from somatic cells. The increase in the number of iPSCs was dependent on the reduction of p53 levels, the tumor suppressor protein that triggers apoptosis via multiple pathways [28]. In the presence of ascorbic acid, in vitro cultured cells express Jhdm1a/1b, two histone demethylases required for iPSCs production [29]. It was also reported that ascorbic acid markedly increases glial proliferation, neurite growth, and the number of tyrosine hydroxylase staining in mesencephalic cultures [30]. Collectively, these results suggest that vitamin C can regulate positively stem cell generation and proliferation.
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