Characterization of companion animal pluripotent stem cells

Abstract

Pluripotent stem cells have the capacity to grow indefinitely in culture and differentiate into derivatives of the three germ layers. These properties underpin their potential to be used in regenerative medicine. Originally derived from early embryos, pluripotent stem cells can now be derived by reprogramming an adult cell back to a pluripotent state. Companion animals such as horses, dogs, and cats suffer from many injuries and diseases for which regenerative medicine may offer new treatments. As many of the injuries and diseases are similar to conditions in humans the use of companion animals for the experimental and clinical testing of stem cell and regenerative medicine products would provide relevant animal models for the translation of therapies to the human field. In order to fully utilize companion animal pluripotent stem cells robust, standardized methods of characterization must be developed to ensure that safe and effective treatments can be delivered. In this review we discuss the methods that are available for characterizing pluripotent stem cells and the techniques that have been applied in cells from companion animals. We describe characteristics which have been described consistently across reports as well as highlighting discrepant results. Significant steps have been made to define the in vitro culture requirements and drive lineage specific differentiation of pluripotent stem cells in companion animal species. However, additional basic research to compare pluripotent stem cell types and define characteristics of pluripotency in companion animal species is still required. V C 2017 International Society for Advancement of Cytometry

Genetic signatures of evolution of the pluripotency gene regulating network across mammals

“…The characteristics of mammalian PSCs may differ among species (Ezashi et al 2016;Weinberger et al 2016;Paterson et al 2018) and reduction in selective constraint highlights evolutionary flexibility and innovation (Lahti et al 2009;Moczek 2010;Hunt et al 2011). For example, pluripotent state of PSCs can be described with multiple types such as naive or primed states, and the amenabilities of the pluripotent state in vitro differ between species (Boroviak et al 2015).…”

“…Parts of the PGRN seem to be evolutionary conserved across mammals because iPSCs from different taxonomic groups have been derived using human genetic sequences of identical sets of transcription factors (OCT4, SOX2, KLF4, and MYC; collectively referred to as OSKM). On the other hand, different pluripotent states and configurations are observed across different species (Ezashi et al 2016;Weinberger et al 2016;Paterson et al 2018), indicating diversity and uniqueness of the PGRN among species. However, our understandings of the PGRN are extensively limited to primates and rodents (Manor et al 2015), rather than considering the evolutionary history of the mammalian PGRN across different taxonomic groups.…”

Gametes from stem cells: Status and applications in animal reproduction

“…Sheep ES‐like cells with some signs of pluripotency and medium‐term proliferation but no teratoma formation or chimera contribution have been reported (Zhao et al, ). In horse, attempts to derive ESCs have resulted in cells with either unproven or deficient potential for in vivo pluripotency (reviewed by Paterson, Kafarnik, & Guest, ). In small companion species, cat embryonic cells have shown very limited proliferation (reviewed by Paterson et al, ), while dog ESCs with high proliferative ability and proven potential for in vitro and in vivo pluripotency have been in use since 2009 (Vaags et al, ).…”

Morpho‐Functional Characteristics of Bone Marrow Multipotent Mesenchymal Stromal Cells after Activation or Inhibition of Epidermal Growth Factor and Toll‐Like Receptors or Treatment with DNA Intercalator Cisplatin

“…During MET, МSCs have several cycles of proliferations, differentiating into epithelial-like phenotype and repairing the injured area (5,6). Inflammation may induce the МSCs' transformation during the initial stages of wound healing (10). Inflammation may induce the МSCs' transformation during the initial stages of wound healing (10).…”

“…However, МSCs may be engaged via MET into tumorigenesis: their transformation into cancer cells subsequent growth of carcinoma with epithelial phenotype (7,8) or formation of inner mesenchymal stroma (tumor-associated fibroblasts) (9). Inflammation may induce the МSCs' transformation during the initial stages of wound healing (10).…”