Transgenic mammalian species, generated by somatic cell cloning, in biomedicine, biopharmaceutical industry and human nutrition/dietetics - recent achievements

Abstract

Somatic cell cloning technology in mammals promotes the multiplication of productively-valuable genetically engineered individuals, and consequently allows also for standardization of transgenic farm animal-derived products, which, in the context of market requirements, will have growing significance. Gene farming is one of the most promising areas in modern biotechnology. The use of live bioreactors for the expression of human genes in the lactating mammary gland of transgenic animals seems to be the most cost-effective method for the production/processing of valuable recombinant therapeutic proteins. Among the transgenic farm livestock species used so far, cattle, goats, sheep, pigs and rabbits are useful candidates for the expression of tens to hundreds of grams of genetically-engineered proteins or xenogeneic biopreparations in the milk. At the beginning of the new millennium, a revolution in the treatment of disease is taking shape due to the emergence of new therapies based on recombinant human proteins. The ever-growing demand for such pharmaceutical or nutriceutical proteins is an important driving force for the development of safe and large-scale production platforms. The aim of this paper is to present an overall survey of the state of the art in investigations which provide the current knowledge for deciphering the possibilities of practical application of the transgenic mammalian species generated by somatic cell cloning in biomedicine, the biopharmaceutical industry, human nutrition/dietetics and agriculture.

Effect of histone deacetylase inhibitor romidepsin on thein vitrogrowth of foetal fibroblast cells and early development of porcine-cloned embryos

“…But, the low cloning efficiency and reconstructed embryo dysplasia resulting from incomplete reprogramming of the donor nucleus are responsible for the slow pace of development in the field of porcine SCNT (Hill et al 2000;Yang et al 2007). Different studies have shown that the most important and effective way to promote epigenetic reprogramming of donor cell nuclei and restore their totipotency is to change the histone acetylation or DNA methylation status of somatic cell genome before and/or after its transplantation into a cytoplasm of enucleated recipient oocyte (Samiec et al 2012;Staszkiewicz et al 2013;Zhou et al 2014;Samiec et al 2015). Alone treatment of donor cells with different concentrations of FK228 for 24 h did not obviously improve the cleavage rate of cloned embryos.…”

“…Somatic cell nuclear transfer (SCNT) is of profound significance to save endangered animals, create transgenic animals, duplicate elite livestock, and provide tools and materials for basic research in biomedical field (Sameic 2005;Samiec & Skrzyszowska 2011a, 2011b. Transgenic cloned pigs are of great importance in animal husbandry and are also regarded as an ideal model for human diseases due to these characteristics of abundant resources, high fecundity, and physiological and anatomical structure similarities to humans (Samiec & Skrzyszowska 2011a;Samiec et al 2012;Kurome et al 2013;Ma et al 2016).…”

“…Transgenic cloned pigs are of great importance in animal husbandry and are also regarded as an ideal model for human diseases due to these characteristics of abundant resources, high fecundity, and physiological and anatomical structure similarities to humans (Samiec & Skrzyszowska 2011a;Samiec et al 2012;Kurome et al 2013;Ma et al 2016). Viable SCNTderived offspring were successfully obtained in pigs 16 years ago (Betthauser et al 2000;Onishi et al 2000;Polejaeva et al 2000).…”

Chimerism in piglets developed from aggregated cloned embryos

“…A hallmark of the pluripotency of embryonic stem (ES) cells and induced pluripotent stem (iPS) cells was demonstrated by the observation that their subclonal cultures are distributed into all embryonic tissues including germ cells when reintroduced into other host embryos . In addition to the investigation of embryo pluripotency characteristics, chimeric embryos are also valuable in studies focused on embryogenesis and fetogenesis and in transgenic research . However, reports on porcine chimeras were rare.…”

“…The results show that chimeric pigs can be produced by aggregating cloned embryos and that the developmental capability of the cloned embryo in the subsequent chimeric development could be affected by the growth characteristics of its donor cell.A hallmark of the pluripotency of embryonic stem (ES) cells and induced pluripotent stem (iPS) cells was demonstrated by the observation that their subclonal cultures are distributed into all embryonic tissues including germ cells when reintroduced into other host embryos [1,2]. In addition to the investigation of embryo pluripotency characteristics, chimeric embryos are also valuable in studies focused on embryogenesis and fetogenesis [3][4][5] and in transgenic research [4,[6][7][8]. However, reports on porcine chimeras were rare.…”