The Pursuit of ES Cell Lines of Domesticated Ungulates

Abstract

In contrast to differentiated cells, embryonic stem cells (ESC) maintain an undifferentiated state, have the ability to self-renew, and exhibit pluripotency, i.e., they can give rise to most if not all somatic cell types and to the germ cells, egg and sperm. These characteristics make ES cell lines important resources for the advancement of human regenerative medicine, and, if established for domesticated ungulates, would help make possible the improvement of farm animals through their contribution to genetic engineering technology. Combining other genetic engineering technologies, such as somatic cell nuclear transfer with ESC technology may result in synergistic gains in the ability to precisely make and study genetic alterations in mammals. Unfortunately, despite significant advances in our understanding of human and mouse ESC, the derivation of ES cell lines from ungulate species has been unsuccessful. This may result from a lack of understanding of species-specific mechanisms that promote or influence cell pluripotency. Thorough molecular characterizations, including the elucidation of stem cell "marker" signaling cascade hierarchy, species-appropriate pluripotency markers, and pluripotency-associated chromatin alterations in the genomes of ungulate species, should improve the chances of developing efficient, reproducible technologies for the establishment of ES cell lines of economically important species like the pig, cow, goat, sheep and horse.

Generation of Induced Pluripotent Stem Cell Lines from Tibetan Miniature Pig

“…Pig organs have also raised enormous interest for xenotransplantation: use of transgenic pigs lacking ␣(1-3)-galactosyltransferase gene, a major xenoantigen involved in acute rejection, holds optimism regarding effectiveness of more comprehensive genetic manipulations (20). Isolation of fully competent ESC from pigs or animal species apart from mouse, human, monkey, and more recently the rat, has proven impossible despite years of maintained effort (21,22). Consequently, porcine genetic manipulation can only be achieved through laborious and inefficient somatic cell nuclear transfer (23).…”

Prospectus of cultured meat—advancing meat alternatives

“…As of yet none of these processes, though detailed, have been tested, this review introduces the techniques so far proposed. This is partially because livestock animal cell lines have not been well-established in vitro (Talbot and Blomberg 2008) and because growing muscle cells ex vivo on a large scale is certainly a vast and unexplored undertaking. The technical demands of large scale production are unseen in the world of medical research, where most efforts in growing tissue ex vivo have been directed.…”

“…Although embryonic stem cells have been cultured for many generations but so far it has not been possible to culture cell lines with unlimited self-renewal potential from preimplantation embryos of farm animal species. Until now, true embryonic stem cell lines have only been generated from mouse, rhesus monkey, human and rat embryos (Talbot and Blomberg 2008) but the social resistance to cultured meat obtained from mouse, rat or rhesus monkey will be considerable and will not result in a marketable product. The culture conditions required to keep mouse and human embryonic cells undifferentiated are different from the conditions that will be required for embryonic cells of farm animal species and fundamental research on the early development of embryos of these species can provide clues.…”

Derivation of induced pluripotent stem cells from pig somatic cells

“…This discovery also heralded the prospects of using ESC in regenerative medicine. Despite their undoubted promise as sources of tissue transplants, many road blocks remain to using human ESC as a source of transplant material, especially as a means to test the efficacy of therapies and the safety of the transferred cells in animals whose anatomy and physiology better resemble the human than the mouse (11)(12)(13)(14)(15). The pig is a potentially useful model in this regard because of similarities in organ size, immunology, and whole animal physiology (16)(17)(18).…”

“…As a result, this field of research has languished without major breakthroughs for well over a decade. These difficulties, as well as the potential value of ESC from ungulate species, have been discussed at length in several recent reviews (11,(13)(14)(15)22).…”