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Stem Cells and Nanotechnology
Published in Stavros Hatzopoulos, Andrea Ciorba, Mark Krumm, Advances in Audiology and Hearing Science, 2020
Other authors used HSC to recover HC loss after transient cochlear ischemia in gerbils: The HSC did not transdifferentiate or integrate with the cochlear tissue, but repaired the HC loss, probably through a paracrine effect (Yoshida et al., 2007). Human haematopoietic SC derived from umbilical cord blood (hUCB) were transplanted intravenously in deafened mice: They were recruited in the damaged ear tissue (stria vascularis and spiral ganglion), inducing a morphological recovery of the organ of Corti (Revoltella et al., 2008). Among recruited cells, a small number of heterokaryons was detected in stria vascularis and spiral ganglion, showing fusion events between ExSC and endogenous cells. These results supported the occurrence of paracrine effects in these experimental conditions (Yoshida et al., 2007; Revoltella et al., 2008).
Tumor Angiogenesis
Published in Hans-Inge Peterson, Tumor Blood Circulation: Angiogenesis, Vascular Morphology and Blood Flow of Experimental and Human Tumors, 2020
A further growth factor, epidermal growth factor,55 was eventually isolated because side effects on the skin were noted with crude NGF. When daily injections of EGF were given in a dose of 0.5 mg/1.5 g of body weight to newborn mice for 6 days, marked alteration in epidermal growth was noted. The skin thickened, underwent early keratinization, and the height of the epitelia lining the oral cavity, esophagus, and stomach mucosa increased. Levi-Montalcini55 distinguished growth factors from hormones by the following features. The primary effect of growth factors is to increase growth activity rather than functional activity. Growth factors are important early in life during growth and differentiation of the target cells. Levi-Montalcini55 speculated that similar control mechanisms to those of NGF might exist for all cell types and might function as a primitive integration system. A relationship of metabolites to the growth factors might exist. Such substances, released by poorly organized cells not present as defined organs, might be utilized by other cells as growth factors. The ability to respond to NGF persists even in neuronal-HeLa heterokaryons.60 Cells from dorsal root ganglia of 7-day chick embryos can be fused with HeLa cells by inactivated Sendai virus. Nerve growth factor resulted in the growth of long processes from the neuronal-HeLa heterokaryons.
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
A different approach demonstrating that cell fates are plastic and can be reprogrammed was made by cell fusion. In 1983, Blau et al. fused human amniocytes (cells isolated from the amniotic fluid surrounding the embryo) and murine muscle cells (Blau et al., 1983). These fusion products, referred to as heterokaryons, do not divide – this means that two distinct nuclei remain intact in the cytoplasm, each with a full set of chromosomes. Since the two nuclei are from different species, chromosomes can be distinguished and the impact of one genome on the other can be studied. Blau et al. found that the human amniocytes quickly activated and expressed muscle-specific genes and that this reprogramming of amniocytes is mediated through the joined cytoplasm. These findings were met with great excitement but also scepticism as they showed, in accordance with Gurdon’s report, that cell fate is determined by gene expression rather than gene content. Moreover, these cell fusion experiments indicated that gene expression is regulated by trans-acting repressors or activators and that their balance determines cell fate decisions.
Progress of co-culture systems in cartilage regeneration
Published in Expert Opinion on Biological Therapy, 2018
Jianyu Zou, Bo Bai, Yongchang Yao
Many researchers devote themselves to investigating the underlying mechanisms in direct co-culture systems. Some suppose that the direct cell-cell contact may result in the cell fusion of the different types of cells to form heterokaryons [36,86]. Some believe that direct physical contact facilitates the close intercellular communication and signal transmission among the co-cultured heterologous cells via autocrine and paracrine ways [34,87]. Some note that connexons, expressed by chondrocytes, form gap junctions and enhance cell signal exchange and further improve tissue formation [83,88]. Recently, a comprehensive study was carried out to determine the mechanisms behind co-culture systems [25]. This study employed a cytosolic dye transfer test and connexin 43 (a gap junction protein) staining to confirm that the communication between human articular chondrocytes and human bone marrow-derived MSCs in the direct co-culture system is through gap junctions. Gap junctions are of great importance in cell–cell connections by the exchange of nutrients and the transduction of molecular signals [89].
Enhanced production of tanshinone IIA in endophytic fungi Emericella foeniculicola by genome shuffling
Published in Pharmaceutical Biology, 2018
Pengyu Zhang, Yiting Lee, Xiying Wei, Jinlan Wu, Qingmei Liu, Shanning Wan
Genome shuffling is dependent upon the recursive fusion of protoplasts to carry out recombination. This recursive strategy permits the quick obtainment of phenotypes of interest. The high frequency of protoplast formation and regeneration is the basis of the efficient genome shuffling. When the protoplasts were mixed with PEG solution, they stuck together and then formed paired protoplasts. Later, the plasma membranes in the contact area of protoplasts were dissolved, and the protoplasmic contents were fused. The fusion of two or more cell membranes and the resultant formation of a heterokaryon were observed through a high-power microscope. Subsequently, the nuclei of some paired protoplasts were fused together (karyogamy). Ultimately, the fused protoplasts were turned into single, large, round or oval-shaped structures, respectively (data not shown).
Cancer stem cells (CSCs): key player of radiotherapy resistance and its clinical significance
Published in Biomarkers, 2023
Saminur Hoque, Rajib Dhar, Rishav Kar, Sayantanee Mukherjee, Dattatreya Mukherjee, Nobendu Mukerjee, Sagnik Nag, Namrata Tomar, Saurav Mallik
Until Mistry, the source or genesis of cancer stem cells was unknown. Cancer cells are thought to grow by induced cell fusion, genetic instability, horizontal gene transfer and tumour microenvironment-affecting factors, according to certain theories (Bjerkvig et al. 2005). Cell–cell fusion plays an important function in immune response, tissue growth and placenta formation in the biological system (Blau et al. 1999, Alvarez-Dolado et al. 2003, Vassilopoulos et al. 2003, Weimann et al. 2003, Camargo et al. 2004, O’Malley and Scott 2004, Pomerantz et al. 2004, Wagers et al. 2004). According to current research, fusing cancer cells and lymphocytes boosts phenotypic and genotypic change, which leads to cancer progression (Warner 1975, Larizza et al. 1984, Rachkovsky et al. 1997, Duelli et al. 2003). This in vitro union of stem cells with cancer cells (Aractingi et al. 2005) resulted in the formation of a novel class of cells that carry heterokaryons and convert synkaryons. Cancer stem cell development is linked to the Notch, Wnt and Hedgehog signalling pathways (Briscoe et al.1999, Yun et al. 2002, Daikoku et al. 2004, Zákány et al. 2004). In addition, various external substances, such as interleukin 4 (IL4), impact the cell fusion process (Horsley et al. 2003, 2004). The changes at the chromosomal level cause genetic instability, which is one of the characteristics of cancer cells (Sen 2000). This change occurs at the level of tumour suppression or protooncogene mutation (Hansen and Cavenee 1988). The genetic mutation had an impact on epigenetic levels, allowing the cancer cell to begin clonal diversity (Fomchenko et al. 2005). Cancer is initiated by epigenetic change, chromosomal disruption and mutation; however, many factors influence the rate of malignancy, including a wide range of variability in the tumour microenvironment. Another mechanism that contributes to the creation of CSCs is horizontal gene transfer (Bergsmedh et al. 2002). Extra transformation and transmission lead to multidrug resistance via genomic alteration (Lake et al. 1999, Ochman et al. 2000, Palmer et al. 2010). Experiments reveal that oncogenic virus, such as Epstein–Barr virus (EBV), cause cancer cell growth and p53 expression to decrease in vitro and in vivo (Holmgren et al. 1999, Bergsmedh et al. 2001). Tumour microenvironment (TME) related IL-6 and NF-kB maintain and alive CSCs population in TME and influence non-tumour cells to become CSCs (Moore et al. 2011). Still, additional study is needed to have a complete picture of the tumour microenvironment’s activity and how it affects cancer growth. Recent research evidence suggests that in oral cancer after radiotherapy Oct4 activation participates cancer stem cell development and also maintains the stemness of CSCs and active DNA repairing mechanism after radiotherapy (Nathansen et al. 2021).