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hiPSC-Based Disease Models as Replacements of Animal Models
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hiPSC-Based Disease Models as Replacements of Animal Models

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: 30 July 2024 | Viewed by 3410

Special Issue Editor

Dr. Rivka Ofir

E-Mail Website1 Website2
Guest Editor
Regenerative Medicine & Stem Cell Research Center, Ben-Gurion University and Dead Sea & Arava Science Center, Beer Sheva 84105, Israel
Interests: reprogramming; differentiation; Brain Blood Barrier (BBB); iPSC; drug discovery; disease in a dish model
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

This Special Issue will cover the topics related to hiPSC-based models for drug discovery in-line with the new legislation statement of the "FDA no longer has to require animal testing for new drugs".

This Special Issue will accept works that describe hiPSC-based models for drug discovery for human diseases that can actually serve as replacements for animal preclinical trials.

The hiPSC-based disease models will have endpoint/readout methods for the validation of the potential of leads to becoming drugs.

The hiPSC-based disease models will be close enough to be accepted by the FDA as indications for new drugs for clinical trials.  

The hiPSC-based disease models will include the relevant cells that are part of the organ that is the subject of the disease, such as brain organoids, liver organoids, heart organoids, etc.

We are looking also for papers in which the endpoint/readout of the new leads for drugs identified in hiPSC-based disease models will include methods with which to measure efficacy and/or toxicity and/or BBB transfer.

Dr. Rivka Ofir
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • hiPSC-based disease 3D models
  • drug cytotoxicity and efficacy
  • heart disease 3D models
  • brain disease 3D models
  • readout of drug cytotoxicity and efficacy
  • drugs crossing the blood–brain barrier, iPSCs
  • BBB
  • organoid
  • differentiation
  • muscle cells
  • neurons
  • drug discovery
  • direct differentiation
  • stem cell markers
  • tissue markers

Published Papers (2 papers)

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Research

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14 pages, 3062 KiB  
Article
PAPP-A-Specific IGFBP-4 Proteolysis in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes
by Daria A. Adasheva, Olga S. Lebedeva, Daria V. Goliusova, Alexander B. Postnikov, Maria V. Teriakova, Irina V. Kopylova, Maria A. Lagarkova, Alexey G. Katrukha and Daria V. Serebryanaya
Int. J. Mol. Sci. 2023, 24(9), 8420; https://doi.org/10.3390/ijms24098420 - 08 May 2023
Viewed by 1635
Abstract
The insulin-like growth factors IGF-I and IGF-II—as well as their binding proteins (IGFBPs), which regulate their bioavailability—are involved in many pathological and physiological processes in cardiac tissue. Pregnancy-associated plasma protein A (PAPP-A) is a metalloprotease that preferentially cleaves IGFBP-4, releasing IGF and activating [...] Read more.
The insulin-like growth factors IGF-I and IGF-II—as well as their binding proteins (IGFBPs), which regulate their bioavailability—are involved in many pathological and physiological processes in cardiac tissue. Pregnancy-associated plasma protein A (PAPP-A) is a metalloprotease that preferentially cleaves IGFBP-4, releasing IGF and activating its biological activity. Previous studies have shown that PAPP-A-specific IGFBP-4 proteolysis is involved in the pathogenesis of cardiovascular diseases, such as ischemia, heart failure, and acute coronary syndrome. However, it remains unclear whether PAPP-A-specific IGFBP-4 proteolysis participates in human normal cardiomyocytes. Here, we report PAPP-A-specific IGFBP-4 proteolysis occurring in human cardiomyocytes derived from two independent induced pluripotent cell lines (hiPSC-CMs), detected both on the cell surface and in the cell secretome. PAPP-A was measured by fluoroimmune analysis (FIA) in a conditioned medium of hiPSC-CMs and was detected in concentrations of up to 4.3 ± 1.33 ng/mL and 3.8 ± 1.1 ng/mL. The level of PAPP-A-specific IGFBP-4 proteolysis was determined as the concentration of NT-IGFBP-4 proteolytic fragments using FIA for a proteolytic neo-epitope-specific assay. We showed that PAPP-A-specific IGFBP-4 proteolysis is IGF-dependent and inhibited by EDTA and 1,10-phenanthroline. Therefore, it may be concluded that PAPP-A-specific IGFBP-4 proteolysis functions in human normal cardiomyocytes, and hiPSC-CMs contain membrane-bound and secreted forms of proteolytically active PAPP-A. Full article
(This article belongs to the Special Issue hiPSC-Based Disease Models as Replacements of Animal Models)
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Review

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18 pages, 325 KiB  
Review
Human-Induced Pluripotent Stem Cells in Plastic and Reconstructive Surgery
by Nina Hadzimustafic, Andrew D’Elia, Valentina Shamoun and Siba Haykal
Int. J. Mol. Sci. 2024, 25(3), 1863; https://doi.org/10.3390/ijms25031863 - 03 Feb 2024
Viewed by 1263
Abstract
A hallmark of plastic and reconstructive surgery is restoring form and function. Historically, tissue procured from healthy portions of a patient’s body has been used to fill defects, but this is limited by tissue availability. Human-induced pluripotent stem cells (hiPSCs) are stem cells [...] Read more.
A hallmark of plastic and reconstructive surgery is restoring form and function. Historically, tissue procured from healthy portions of a patient’s body has been used to fill defects, but this is limited by tissue availability. Human-induced pluripotent stem cells (hiPSCs) are stem cells derived from the de-differentiation of mature somatic cells. hiPSCs are of particular interest in plastic surgery as they have the capacity to be re-differentiated into more mature cells, and cultured to grow tissues. This review aims to evaluate the applications of hiPSCs in the plastic surgery context, with a focus on recent advances and limitations. The use of hiPSCs and non-human iPSCs has been researched in the context of skin, nerve, vasculature, skeletal muscle, cartilage, and bone regeneration. hiPSCs offer a future for regenerated autologous skin grafts, flaps comprised of various tissue types, and whole functional units such as the face and limbs. Also, they can be used to model diseases affecting tissues of interest in plastic surgery, such as skin cancers, epidermolysis bullosa, and scleroderma. Tumorigenicity, immunogenicity and pragmatism still pose significant limitations. Further research is required to identify appropriate somatic origin and induction techniques to harness the epigenetic memory of hiPSCs or identify methods to manipulate epigenetic memory. Full article
(This article belongs to the Special Issue hiPSC-Based Disease Models as Replacements of Animal Models)
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