Stem Cells and Cell Conversion in Livestock
The main drive to study stem cells is their possible use as therapeutic agents. Within veterinary medicine, a direct medicinal use of stem cells is reserved to companion species. Domestic ungulates like ruminants and pig are often used for preclinical research.
A stem cell is an unspecialized cell type able to undergo asymmetrical divisions: one cell is identical to its mother; the other begins its transformation toward one or more cell types capable of specific functions.
Physiologically, small populations of stem cells are present in each organ, and their function is to counteract the physiological wear and tear. These are named organ-specific stem cells and can be isolated from any animal species as well as in humans.
Embryonic stem cells are not a physiological cell type and are derived from early embryos or can be generated artificially (induced pluripotent cells) by inducing a somatic cell to overexpress four specific pluripotency-related genes. They can proliferate indefinitely if kept undifferentiated or can give rise to any other cell type when cultured in the appropriate conditions or transplanted back into an embryo. However, as opposed to organ-specific stem cells, pluripotent stem cells have so far been difficult to obtain in any species other than humans and laboratory rodents.
In order to circumvent the lack of pluripotent cells in livestock species as well as their inherent susceptibility to culture-induced alterations and tumorigenic transformation, novel techniques of cell conversions have been developed that work effectively with no species-specific limitations. Epigenetic mechanisms are used to enhance cell plasticity so that the exposure to adequate culture conditions can transform easily accessible dermal fibroblasts into a wide range of different cell types. Their lack of permanent pluripotency makes them promising candidates for safe therapeutic applications in all species including livestock.
KeywordsStem cell Regenerative medicine Pluripotency Organ-specific Epigenetic modifications Small molecules Cell conversion
Carraresi Foundation and European Foundation for the Study of Diabetes (EFSD). The authors are members of the COST Actions FA1201 Epiconcept: Epigenetics and Periconception Environment, BM1308 Sharing Advances on Large Animal Models (SALAAM), CM1406 Epigenetic Chemical Biology (EPICHEM), and CA16119 In vitro 3-D total cell guidance and fitness (CellFit). A special thanks to Dr. G. Pennarossa, University of Milan, for the help in the preparation of the text and images.
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