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Molecular Research in Stem Cells

A special issue of Current Issues in Molecular Biology (ISSN 1467-3045). This special issue belongs to the section "Biochemistry, Molecular and Cellular Biology".

Deadline for manuscript submissions: closed (29 February 2024) | Viewed by 3510

Special Issue Editors


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Guest Editor
Yale School of Medicine, Yale University, New Haven, CT 06510, USA
Interests: genome engineering; cell therapy; embryonic stem cell; genetic screening; mouse model

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Guest Editor
Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China
Interests: genome editing; hematopoietic stem cell; gene therapy; thalassemia; embryonic stem cell; genetic screening

Special Issue Information

Dear colleagues,

Molecular research in stem cells is a broad and dynamic field that encompasses the study of the molecular mechanisms governing stem cell biology, differentiation, and their potential applications in regenerative medicine, disease modeling, and drug discovery. Stem cells are unique cells with the ability to self-renew and differentiate into various cell types, making them a valuable resource for understanding development and tissue repair.

Some of the key aspects of molecular research in stem cells include the following: (a) Characterization of different types of stem cells, such as embryonic stem cells, induced pluripotent stem cells, and various adult stem cell populations utilizing molecular techniques. This involves analyzing gene expression profiles, surface markers, and epigenetic modifications. (b) Investigation of the molecular mechanisms underlying stem cell differentiation, with the aim of harnessing their potential for regenerative medicine. Stem cells, particularly iPSCs, can be derived from patients with various diseases which benefit disease modeling. The advent of genome editing technologies such as CRISPR-Cas9 has revolutionized stem cell research. (c) Molecular research in stem cells aims to translate laboratory findings into clinical applications. This involves addressing safety, scalability, and regulatory hurdles for therapies based on stem cells.

Overall, molecular research in stem cells is an interdisciplinary field that combines biology, genetics, genomics, epigenetics, and bioinformatics to uncover the molecular intricacies governing stem cell behavior and harness their therapeutic potential. It continues to advance our understanding of development and disease, while offering exciting possibilities for medical treatments and regenerative therapies.

Dr. Meizhu Bai
Dr. Yuxuan Wu
Guest Editors

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. Current Issues in Molecular Biology is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2200 CHF (Swiss Francs). 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

  • stem cell biology
  • self-renew and differentiation
  • regenerative medicine
  • disease modeling
  • embryonic stem cells
  • induced pluripotent stem cells
  • adult stem cells
  • genetics and epigenetics
  • gene editing

Published Papers (4 papers)

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Research

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27 pages, 6460 KiB  
Article
Extracellular Vesicles Isolated from Equine Adipose-Derived Stromal Stem Cells (ASCs) Mitigate Tunicamycin-Induced ER Stress in Equine Corneal Stromal Stem Cells (CSSCs)
by Justyna M. Meissner, Aleksandra Chmielińska, Ron Ofri, Anna Cisło-Sankowska and Krzysztof Marycz
Curr. Issues Mol. Biol. 2024, 46(4), 3251-3277; https://doi.org/10.3390/cimb46040204 - 9 Apr 2024
Viewed by 732
Abstract
Corneal ulcers, characterized by severe inflammation of the cornea, can lead to serious, debilitating complications and may be vision-threatening for horses. In this study, we aimed to investigate the role of endoplasmic reticulum (ER) stress in corneal stem progenitor cell (CSSC) dysfunction and [...] Read more.
Corneal ulcers, characterized by severe inflammation of the cornea, can lead to serious, debilitating complications and may be vision-threatening for horses. In this study, we aimed to investigate the role of endoplasmic reticulum (ER) stress in corneal stem progenitor cell (CSSC) dysfunction and explore the potential of equine adipose-derived stromal stem cell (ASC)-derived extracellular vesicles (EVs) to improve corneal wound healing. We showed that CSSCs expressed high levels of CD44, CD45, and CD90 surface markers, indicating their stemness. Supplementation of the ER-stress-inducer tunicamycin to CSSCs resulted in reduced proliferative and migratory potential, accumulation of endoplasmic reticulum (ER)-stressed cells in the G0/G1 phase of the cell cycle, increased expression of proinflammatory genes, induced oxidative stress and sustained ER stress, and unfolded protein response (UPR). Importantly, treatment with EVs increased the proliferative activity and number of cells in the G2/Mitosis phase, enhanced migratory ability, suppressed the overexpression of proinflammatory cytokines, and upregulated the anti-inflammatory miRNA-146a-5p, compared to control and/or ER-stressed cells. Additionally, EVs lowered the expression of ER-stress master regulators and effectors (PERK, IRE1, ATF6, and XBP1), increased the number of mitochondria, and reduced the expression of Fis-1 and Parkin, thereby promoting metabolic homeostasis and protecting against apoptosis in equine CSSCs. Our findings demonstrate that MSCs-derived EVs represent an innovative and promising therapeutic strategy for the transfer of bioactive mediators which regulate various cellular and molecular signaling pathways. Full article
(This article belongs to the Special Issue Molecular Research in Stem Cells)
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14 pages, 3646 KiB  
Article
Inflammation and Starvation Affect Housekeeping Gene Stability in Adipose Mesenchymal Stromal Cells
by Enrico Ragni, Simona Piccolo, Michela Taiana, Caterina Visconte, Giulio Grieco and Laura de Girolamo
Curr. Issues Mol. Biol. 2024, 46(1), 842-855; https://doi.org/10.3390/cimb46010054 - 19 Jan 2024
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Abstract
Due to the scientific success of in vitro and in vivo model studies, the interest in using mesenchymal stromal cells (MSCs) for the treatment of orthopaedic conditions is growing. In the context of osteoarthritis (OA), MSCs, and, in particular, those derived from adipose [...] Read more.
Due to the scientific success of in vitro and in vivo model studies, the interest in using mesenchymal stromal cells (MSCs) for the treatment of orthopaedic conditions is growing. In the context of osteoarthritis (OA), MSCs, and, in particular, those derived from adipose tissues (ASCs), have found broader access to clinical use as active components of minimally manipulated orthobiologics, as well as clinically expanded cell preparations, or to collect their released factors (secretome) for cell-free approaches. In this regard, while both inflammatory priming and starvation are common strategies used to empower cell potency or collect the secretome, respectively, little is known about the possible influence of these approaches on the stability of housekeeping genes (HKGs) for molecular studies able to fingerprint cell phenotype or potency. In this report, the reliability of five commonly used HKGs (ACTB, B2M, GAPDH, HPRT1 and RPLP0) was tested in ASCs cultured under standard protocol after inflammatory priming or starvation. Gene expression data were computed with four different applets able to rank genes depending on their stability in either single or combined conditions. The obtained final ranking suggests that for each treatment, a specific HKG is needed, and that starvation is the condition with the stronger effect on HKGs’ stability and, therefore, reliability. The normalization effect of proper HKGs’ use was then validated on three genes involved in OA and whose product is released by ASCs. Overall, data presented herein confirm that the choice of the best HKG has to be carefully considered and that each specific condition has to be tested to identify the most reliable candidate. Full article
(This article belongs to the Special Issue Molecular Research in Stem Cells)
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10 pages, 12676 KiB  
Communication
NRG1 Regulates Proliferation, Migration and Differentiation of Human Limbal Epithelial Stem Cells
by Bofeng Wang, Huizhen Guo, Zhuo Han, Siqi Wu, Jiafeng Liu, Zesong Lin, Fengjiao An, Jin Zhu and Mingsen Li
Curr. Issues Mol. Biol. 2023, 45(12), 10121-10130; https://doi.org/10.3390/cimb45120632 - 14 Dec 2023
Viewed by 807
Abstract
Limbal epithelial stem/progenitor cells (LESCs) proliferate, migrate and differentiate into mature corneal epithelium cells (CECs) that cover the ocular surface. LESCs play a crucial role in the maintenance and regeneration of the corneal epithelium, and their dysfunction can lead to various corneal diseases. [...] Read more.
Limbal epithelial stem/progenitor cells (LESCs) proliferate, migrate and differentiate into mature corneal epithelium cells (CECs) that cover the ocular surface. LESCs play a crucial role in the maintenance and regeneration of the corneal epithelium, and their dysfunction can lead to various corneal diseases. Neuregulin 1 (NRG1) is a member of the epidermal growth factor family that regulates the growth and differentiation of epithelial tissues. Here, we depicted the dynamic transcriptomic profiles during human CEC differentiation, identifying six gene co-expression modules that were specific to different differentiation stages. We found that the expression of NRG1 was high in human LESCs and decreased dramatically upon differentiation. Knockdown of NRG1 significantly inhibited LESC proliferation and upregulated the expression of the terminal differentiation marker genes KRT3, KRT12 and CLU. In addition, the scratch wound closure assay showed that knockdown of NRG1 attenuated wound closure of LESCs over 24 h. Together, we dissected the transcriptional regulatory dynamics during CEC differentiation and identified NRG1 as a key regulator that promoted LESC proliferation and migration and maintained the undifferentiated state. Full article
(This article belongs to the Special Issue Molecular Research in Stem Cells)
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Review

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13 pages, 1254 KiB  
Review
Association between Donor Age and Osteogenic Potential of Human Adipose Stem Cells in Bone Tissue Engineering
by Md Abdus Sattar, Lara F. Lingens, Vincent G. J. Guillaume, Rebekka Goetzl, Justus P. Beier and Tim Ruhl
Curr. Issues Mol. Biol. 2024, 46(2), 1424-1436; https://doi.org/10.3390/cimb46020092 - 6 Feb 2024
Viewed by 693
Abstract
Adipose stem cells (ASCs) have multilineage differentiation capacity and hold great potential for regenerative medicine. Compared to bone marrow-derived mesenchymal stem cells (bmMSCs), ASCs are easier to isolate from abundant sources with significantly higher yields. It is generally accepted that bmMSCs show age-related [...] Read more.
Adipose stem cells (ASCs) have multilineage differentiation capacity and hold great potential for regenerative medicine. Compared to bone marrow-derived mesenchymal stem cells (bmMSCs), ASCs are easier to isolate from abundant sources with significantly higher yields. It is generally accepted that bmMSCs show age-related changes in their proliferation and differentiation potentials, whereas this aspect is still controversial in the case of ASCs. In this review, we evaluated the existing data on the effect of donor age on the osteogenic potential of human ASCs. Overall, a poor agreement has been achieved because of inconsistent findings in the previous studies. Finally, we attempted to delineate the possible reasons behind the lack of agreements reported in the literature. ASCs represent a heterogeneous cell population, and the osteogenic potential of ASCs can be influenced by donor-related factors such as age, but also gender, lifestyle, and the underlying health and metabolic state of donors. Furthermore, future studies should consider experimental factors in in vitro conditions, including passaging, cryopreservation, culture conditions, variations in differentiation protocols, and readout methods. Full article
(This article belongs to the Special Issue Molecular Research in Stem Cells)
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