Porcine induced pluripotent stem cells may bridge the gap between mouse and human iPS

Abstract

SummaryRecently, three independent laboratories reported the generation of induced pluripotent stem cells (iPSCs) from pig (Sus scrofa). This finding sums to the growing list of species (mouse, human, monkey, and rat, in this order) for which successful reprogramming using exogenous factors has been achieved, and multiple others are possibly forthcoming. But apart from demonstrating the universality of the network identified by Shinya Yamanaka, what makes the porcine model so special? On one side, pigs are an agricultural commodity and have an easy and affordable maintenance compared with nonhuman primates that normally need to be imported. On the other side, resemblance (for example, size of organs) of porcine and human physiology is striking and because pigs are a regular source of food the ethical concerns that still remain in monkeys are not applicable. Besides, the prolonged lifespan of pigs compared with other domestic species can allow exhaustive follow up of side effects after transplantation. Porcine iPSCs may thus fill the gap between the mouse model, which due to its ease is preferred for mechanistic studies, and the first clinical trials using iPSCs in humans. However, although these studies are relevant and have created significant interest they face analogous problems that we discuss herein together with potential new directions. THE DISCOVERY OF INDUCED PLURIPOTENCYThe isolation of mouse and human embryonic stem cells (ESCs) in 1981 and 1998, respectively, has supposed a tremendous scientific advance (1, 2). The longstanding promise of ESCs has been to replace diseased cells and organs usingunless differentiation is triggered-an unlimited source of selfrenewing cells which have the ability to produce all tissues that compose an adult individual (pluripotency). In addition, ESCs have provided a new and powerful model for studying cell fate determination, epigenetic regulation, and disease. Remarkably, mouse ESCs also initiated mammalian genetic manipulation by means of homologous recombination. However, at least in humans, ESCs have ignited a debate that seriously hampered both clinical application and research (3, 4). To avoid controversy, scientists have pursued the generation of ESC-like cells from terminally differentiated (somatic) cells using varied methods [fusion with ESCs, somatic cell nuclear transfer (SCNT), and iPS] that hereafter are generically referred to as nuclear reprogramming or reprogramming (5, 6).Several decades ago, pioneer experiments by Briggs, King, and Gurdon demonstrated that transfer of the nucleus from a frog somatic cell into an enucleated egg can allow the development of this egg to a heartbeat-stage tadpole (7). These experiments set the arena for intensive research that culminated in 1997 with the birth of Dolly the sheep using SCNT (5). Theoretically, SCNT-derived human blastocysts could also be used to produce patient-specific ESC-like cells less constrained by ethical concerns, but the technique is more challenging in humans than in other species and the scarci...

BIX-01294 increases pig cloning efficiency by improving epigenetic reprogramming of somatic cell nuclei

“…Advances in pig genome annotation, genetic modification (GM) of pig cells and somatic cell nuclear transfer (SCNT), have facilitated the generation of GM pigs for various biomedical applications. However, the establishment of porcine embryonic stem cells (ESCs) has proven elusive, despite decades of intense trials, and a similar lack of success has been observed with other ungulate species (Esteban et al 2010). The generation of GM pigs primarily relies on homologous recombination in somatic cells, followed by SCNT.…”

Generation and genetic modification of induced pluripotent stem cells

“…The iPSC models will have an effect on human iPSCs research, because they may not only serve to bridge murine and human iPSCs as model systems [112] but also help --in a contrast and compare approach --to dissect transcription factor networks and signalling pathways in pluripotency and differentiation.…”

Porcine pluripotent stem cells: progress, challenges and prospects

“…Lines of iPSCs have been generated from some domesticated ungulates, such as sheep [90,91] , pigs [87,92,93] and cattle [94,95] . Porcine iPSCs have been produced in many laboratories using various induction methods and show pluripotency to some degree [59,93,96,97] .…”

“…Porcine iPSCs have been produced in many laboratories using various induction methods and show pluripotency to some degree [59,93,96,97] . Porcine iPSCs could pass the test of germline chimera production at the molecular genotyping levels using PCR [42,98] , but stable chimerism remains to be determined.…”