The Promise and Challenge of Induced Pluripotent Stem Cells (iPSCs): 2nd Edition

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: 31 May 2025 | Viewed by 1898

Special Issue Editor


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Guest Editor
1. NanoScience Technology Center, University of Central Florida, 12424 Research Parkway, Suite 400, Orlando, FL 32826, USA
2. Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32816, USA
Interests: stem cell culture; reprogramming; stem cell biology; patch-clamp electrophysiology; synapses differentiation; skeletal muscle; mitochondria; regenerative medicine
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Special Issue Information

Dear Colleagues,

Since the first generation of induced pluripotent stem cells (iPSCs) in 2006, the development of iPSC technology has ushered in a revolutionary new era for studying diseases and developing therapies. Human iPSCs have unmatchable advantages, including pluripotency, potentially limitless expandability, easy accessibility, avoidance of ethical concerns associated with embryonic stem cells or human tissues, and the potential to develop patient-specific models for personalized medicine. These traits make iPSCs an ideal cell source for disease modeling, drug discovery, and regenerative medicine. One quickly evolving field of iPSC technology is the development of human-based in vitro disease models by utilizing patient-iPSCs or those generated by CRISPR/Cas9 gene editing. Through the integration of multidisciplinary technologies, these models are finding increasing applications in pathogenesis study and drug efficacy and toxicity testing. Another is for regenerative medicine, such as autologous or allogenic cell therapy, although they are still challenged by the high standard requirements for quality control. In summary, with the assistance of other technologies, iPSC technology holds great promise for tackling human diseases.

In this Special Issue, studies in all the fields of iPSC technology are invited, from stem cell generation and differentiation to disease modeling and stem cell therapy; progress or challenges encountered; and in vitro or in vivo. Studies reporting breakthrough discoveries in the scientific understanding of iPSC or technological developments will be particularly encouraged. Both research articles and reviews are welcome.

Dr. Xiufang Guo
Guest Editor

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Keywords

  • iPSC
  • cell differentiation
  • disease model
  • disease-in-a-dish
  • body-on-a-chip
  • CRISPR/Cas9
  • gene edition
  • stem cell therapy
  • cell transplantation
  • translational

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Research

18 pages, 3012 KiB  
Article
CRISPR Base Editing to Create Potential Charcot–Marie–Tooth Disease Models with High Editing Efficiency: Human Induced Pluripotent Stem Cell Harboring SH3TC2 Variants
by Camille Loret, Amandine Pauset, Pierre-Antoine Faye, Valérie Prouzet-Mauleon, Ioanna Pyromali, Angélique Nizou, Federica Miressi, Franck Sturtz, Frédéric Favreau, Béatrice Turcq and Anne-Sophie Lia
Biomedicines 2024, 12(7), 1550; https://doi.org/10.3390/biomedicines12071550 - 12 Jul 2024
Viewed by 1322
Abstract
Human induced pluripotent stem cells (hiPSCs) represent a powerful tool to investigate neuropathological disorders in which the cells of interest are inaccessible, such as in the Charcot–Marie–Tooth disease (CMT), the most common inherited peripheral neuropathy. Developing appropriate cellular models becomes crucial in order [...] Read more.
Human induced pluripotent stem cells (hiPSCs) represent a powerful tool to investigate neuropathological disorders in which the cells of interest are inaccessible, such as in the Charcot–Marie–Tooth disease (CMT), the most common inherited peripheral neuropathy. Developing appropriate cellular models becomes crucial in order to both study the disease’s pathophysiology and test new therapeutic approaches. The generation of hiPS cellular models for disorders caused by a single nucleotide variation has been significantly improved following the development of CRISPR-based editing tools. In this study, we efficiently and quickly generated, by CRISPR editing, the two first hiPSCs cellular models carrying alterations involved in CMT4C, also called AR-CMTde-SH3TC2. This subtype of CMT is associated with alterations in the SH3TC2 gene and represents the most prevalent form of autosomal recessive demyelinating CMT. We aimed to develop models for two different SH3TC2 nonsense variants, c.211C>T, p.Gln71* and the most common AR-CMTde-SH3TC2 alteration, c.2860C>T, p.Arg954*. First, in order to determine the best CRISPR strategy to adopt on hiPSCs, we first tested a variety of sgRNAs combined with a selection of recent base editors using the conveniently cultivable and transfectable HEK-293T cell line. The chosen CRISPR base-editing strategy was then applied to hiPSCs derived from healthy individuals to generate isogenic CMT disease models with up to 93% editing efficiency. For point mutation generation, we first recommend to test your strategies on alternative cell line such as HEK-293T before hiPSCs to evaluate a variety of sgRNA-BE combinations, thus boosting the chance of achieving edited cellular clones with the hard-to-culture and to transfect hiPSCs. Full article
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