A few years later, in 2000, Reubinoff et al., independently reported the establishment of hESC lines with similar properties to those of Thomson et al. Although these cultures differentiated after several passages, this was the first report of the successful isolation of human ICM cells and their continued culture in vitro. cultured whole blastocysts on human tubal ampullary epithelium and succeeded in obtaining cells that retained stem cell-like morphology ( Bongso et al., 1994). SCNT-SC: somatic cell nuclear transfer-stem cells iPS: induced pluripotent stem cells.Īround the same time, hESC derivation was also attempted at the National University Hospital in Singapore. ![]() Three pathways to the generation of pluripotent cells are described: hESC derivation from preimplantation-stage embryos (hESC top), derivation after somatic cell nuclear transfer (SCNT-SC middle) and derivation through reprogramming of somatic cells (iPS bottom). It is interesting to note that one of those lines, H9, has been used in clinical trials several years following its derivation. From those embryos, 14 inner cell masses (ICMs) were isolated, and five hESC lines were derived (Fig. The researchers used 36 embryos from patients who underwent IVF, who donated their embryos after completing their treatment. A Thomson was able to report, 4 years later, the derivation of the first hESC line ( Thomson et al., 1998) (Fig. Without any doubts, their experience with rhesus ESCs accelerated their learning curve in primate stem cell handling, and the same team of scientists led by Dr J. Moreover, once released from stem cell culture condition and injected into immunodeficient mice these cells could differentiate spontaneously into derivatives of the three germ layers: endoderm, ectoderm and mesoderm, a test of pluripotency still used to this day ( Thomson et al., 1995). As customary at the time, the line was cultured over a feeder layer of mouse fibroblasts and the scientists were able to show the cells ability to continually grow in culture for more than 1 year. It was here that scientists had derived in 1994 the first primate ESC line from rhesus macaque embryos. In the mid-90s of the last century, one of the most active centers of stem cell research, at that time restricted to mouse work in most countries, was the Wisconsin National Primate Research Center in the USA. The aim of this review is to tell the story of this amazing journey and to reveal its most salient moments through the voice of some of the pioneers in this exciting field. In the 20 years since, some of these promises have been fulfilled, some roadblocks have appeared and some new players have entered the stage of pluripotency. With this review, we hope to inspire young investigators today to continue working on their research in this fascinating topic. This 20th anniversary of the derivation of human embryonic stem cell (hESC) lines offers an ideal opportunity to look back over the past 20 years in this field, as well as to look forward to what the future may hold. Furthermore, we organized interviews with several stem cell scientists at the forefront of basic and clinical research to give the reader a qualitative account of the field, as well as a perspective on the future developments at the cutting edge of research. ![]() We reviewed the history of human pluripotent stem cell (hPSC) derivation, in the context of the scientific and technical environment at the time, giving a historical account of the development of the field of stem cell research with a special emphasis on regenerative medicine and clinical applications.
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