![]() ![]() ![]() In recent years, and especially in the last decade, stem cell research has blossomed into an exciting and promising field. On the other hand, ESCs, iPSCs, and adult stem cells have only been used to generate tissues and organs. Only NTSCs have been used to generate a complete organism: monkeys were grown from NTSCs in China in 2018. To date, five basic categories of stem cells have been put forward following our systematic review of stem cell research: embryonic stem cells (ESCs), very small embryonic-like stem cells (VSELs), nuclear transfer stem cells (NTSCs), reprogrammed stem cells (RSCs), and adult stem cells (ASCs) (see Table 1). Researchers have since detected innate adult stem cells within several organs. In 2012, Shinya Yamanaka (Kyoto University, Japan and Gladstone Institutes, USA) and John Gurdon (Gurdon Institute, Cambridge, UK) were co-recipients of the Nobel Prize for Physiology or Medicine for their discovery that mature cells could be reprogrammed into a pluripotent state. In 2006, induced PSCs (iPSCs) were derived from reprogrammed adult somatic cells with just four basic transcription factors, reduced from 24 factors. Then, in 1998, the first human embryonic stem cells (hESCs) were isolated by James Thomson in the USA. ![]() Several decades later, in 1996, Dolly the sheep was cloned by Keith Campbell, Ian Wilmut, and colleagues at the Roslin Institute of the University of Edinburgh in Scotland, demonstrating the validity of the somatic cell nuclear transfer (SCNT). They found that stem cells derived from mouse bone marrow cells had the ability to differentiate into a variety of cell types, and were thus called pluripotent stem cells (PSCs). McCulloch at the University of Toronto in Canada. Historically, many key milestones have driven progress in the field of stem cell research More than half a century ago, in 1961, the first stem cells were described by Drs. Innovative technologies and real-world applications are emphasized for readers interested in the exciting, promising, and challenging field of stem cells and those seeking guidance in planning future research direction. This review, encompassing the fundamental concepts of regenerative medicine, is intended to provide a comprehensive portrait of important progress in stem cell research and development. Specifically, we highlight the following crucial domains: 1) sources of pluripotent cells 2) next-generation in vivo direct reprogramming technology 3) cell types derived from PSCs and the influence of genetic memory 4) induction of pluripotency with genomic modifications 5) construction of vectors with reprogramming factor combinations 6) enhancing pluripotency with small molecules and genetic signaling pathways 7) induction of cell reprogramming by RNA signaling 8) induction and enhancement of pluripotency with chemicals 9) maintenance of pluripotency and genomic stability in induced pluripotent stem cells (iPSCs) 10) feeder-free and xenon-free culture environments 11) biomaterial applications in stem cell biology 12) three-dimensional (3D) cell technology 13) 3D bioprinting 14) downstream stem cell applications and 15) current ethical issues in stem cell and regenerative medicine. ![]() We begin by discussing experimental advances in the generation and differentiation of pluripotent stem cells (PSCs), next moving to the maintenance of stem cells in different culture types, and finishing with a discussion of three-dimensional (3D) cell technology and future stem cell applications. In this article, we provide a systemic overview of the major recent discoveries in this exciting and rapidly developing field. Over the past 20 years, and particularly in the last decade, significant developmental milestones have driven basic, translational, and clinical advances in the field of stem cell and regenerative medicine. ![]()
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