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Stem Cell Biology in Health and Disease

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: closed (30 September 2022) | Viewed by 9705

Special Issue Editor

Department of Oral Biochemistry and Molecular Biology, Insititute of Translationnal Dental Sciences, Pusan National University School of Dentistry, Yangsan 50612, Korea
Interests: stem cell; regeneration; development; dental stem cell; dental tissue regeneration; dental tissue development; stem cell differentiation

Special Issue Information

Currently, stem cell research holds a great promise in overcoming challenges of incurable diseases and various health issues. Further understanding in stem cell biology will bring more opportunities in advancing novel cures for untreatable ailments. Differentiation of embryonic stem cells allows to investigate the early stage of development and induced pluripotent stem (iPS) cells provide patient-specific disease modeling. Adult stem cells in conventional and three-dimensional organoid culture become affordable sources for the regenerative therapy and the drug screening platform. Genome editing in stem cells holds the potential to cure the disease without relapse.

This Special issue will highlight the stem cell biology related to specific health and disease issues, which may contribute to the development of the future diagnostic or therapeutic applications.

Dr. Il-ho Jang
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.

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Keywords

  • stem cell
  • differentiation
  • development
  • regeneration
  • organoid
  • genome editing
  • disease modeling
  • drug development

Published Papers (4 papers)

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Research

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16 pages, 3530 KiB  
Article
Snap29 Is Dispensable for Self-Renewal Maintenance but Required for Proper Differentiation of Mouse Embryonic Stem Cells
by Yumei Jia, Zhaoyuan Guo, Jiahao Zhu, Guanyu Qin, Wenwen Sun, Yu Yin, Haiying Wang and Renpeng Guo
Int. J. Mol. Sci. 2023, 24(1), 750; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24010750 - 01 Jan 2023
Viewed by 1337
Abstract
Pluripotent embryonic stem cells (ESCs) can self-renew indefinitely and are able to differentiate into all three embryonic germ layers. Synaptosomal-associated protein 29 (Snap29) is implicated in numerous intracellular membrane trafficking pathways, including autophagy, which is involved in the maintenance of ESC pluripotency. However, [...] Read more.
Pluripotent embryonic stem cells (ESCs) can self-renew indefinitely and are able to differentiate into all three embryonic germ layers. Synaptosomal-associated protein 29 (Snap29) is implicated in numerous intracellular membrane trafficking pathways, including autophagy, which is involved in the maintenance of ESC pluripotency. However, the function of Snap29 in the self-renewal and differentiation of ESCs remains elusive. Here, we show that Snap29 depletion via CRISPR/Cas does not impair the self-renewal and expression of pluripotency-associated factors in mouse ESCs. However, Snap29 deficiency enhances the differentiation of ESCs into cardiomyocytes, as indicated by heart-like beating cells. Furthermore, transcriptome analysis reveals that Snap29 depletion significantly decreased the expression of numerous genes required for germ layer differentiation. Interestingly, Snap29 deficiency does not cause autophagy blockage in ESCs, which might be rescued by the SNAP family member Snap47. Our data show that Snap29 is dispensable for self-renewal maintenance, but required for the proper differentiation of mouse ESCs. Full article
(This article belongs to the Special Issue Stem Cell Biology in Health and Disease)
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20 pages, 3692 KiB  
Article
Microcapsule-Based Dose-Dependent Regulation of the Lifespan and Behavior of Adipose-Derived MSCs as a Cell-Mediated Delivery System: In Vitro Study
by Igor Khlusov, Kristina Yurova, Valeria Shupletsova, Olga Khaziakhmatova, Vladimir Malashchenko, Valeriya Kudryavtseva, Marina Khlusova, Gleb Sukhorukov and Larisa Litvinova
Int. J. Mol. Sci. 2023, 24(1), 292; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24010292 - 24 Dec 2022
Cited by 2 | Viewed by 1459
Abstract
The development of “biohybrid” drug delivery systems (DDS) based on mesenchymal stem/stromal cells (MSCs) is an important focus of current biotechnology research, particularly in the areas of oncotheranostics, regenerative medicine, and tissue bioengineering. However, the behavior of MSCs at sites of inflammation and [...] Read more.
The development of “biohybrid” drug delivery systems (DDS) based on mesenchymal stem/stromal cells (MSCs) is an important focus of current biotechnology research, particularly in the areas of oncotheranostics, regenerative medicine, and tissue bioengineering. However, the behavior of MSCs at sites of inflammation and tumor growth is relevant to potential tumor transformation, immunosuppression, the inhibition or stimulation of tumor growth, metastasis, and angiogenesis. Therefore, the concept was formulated to control the lifespan of MSCs for a specific time sufficient for drug delivery to the target tissue by varying the number of internalized microcontainers. The current study addressed the time-dependent in vitro assessment of the viability, migration, and division of human adipose-derived MSCs (hAMSCs) as a function of the dose of internalized polyelectrolyte microcapsules prepared using a layer-by-layer technique. Polystyrene sulfonate (PSS)—poly(allylamine hydrochloride) (PAH)-coated spherical micrometer-sized (diameter ~2–3 µm) vaterite (CaCO3) microcapsules (PAH-PSS)6 with the capping PSS layer were prepared after dissolution of the CaCO3 core template. The Cell-IQ phase contrast imaging results showed that hAMSCs internalized all (PAH-PSS)6 microcapsules saturating the intercellular medium (5–90 particles per cell). A strong (r > 0.7) linear dose-dependent and time-dependent (up to 8 days) regression was observed between the in vitro decrease in cell viability and the number of internalized microvesicles. The approximate time-to-complete-death of hAMSCs at different concentrations of microcapsules in culture was 428 h (1:5 ratio), 339 h (1:10), 252 h (1:20), 247 h (1:45), and 170 h (1:90 ratio). By varying the number of microcontainers loaded into the cells (from 1:10 to 1:90), a dose-dependent exponential decrease in both the movement rate and division rate of hAMSCs was observed. A real-time cell analysis (RTCA) of the effect of (PAH-PSS)6 microcapsules (from 1:5 to 1:20) on hAMSCs also showed a dose- and time-dependent decrease in cell longevity after a 50h study at ratios of 1:10 and 1:20. The incorporation of microcapsules (1:5, 1:20, and 1:45) resulted in a dose-dependent increase in 24–48 h secretion of GRO-α (CXCL1), MIF, and SDF-1α (CXCL12) chemokines in hAMSC culture. In turn, the normalization or inhibition of chemokine secretion occurred after 72 h, except for MIF levels below 5–20 microcapsules, which were internalized by MSCs. Thus, the proposed concept of controlling the lifespan of MSC-based DDS using a dose of internalized PAH-PSS microcapsules could be useful for biomedical applications. (PAH-PSS)6 microcapsule ratios of 1:5 and 1:10 have little effect on the lifespan of hAMSCs for a long time (up to 14–18 days), which can be recommended for regenerative therapy and tissue bioengineering associated with low oncological risk. The microcapsule ratios of 1:20 and 1:45 did not significantly restrict the migratory activity of hAMSCs-based DDS during the time interval required for tissue delivery (up to 4–5 days), followed by cell death after 10 days. Therefore, such doses of microcapsules can be used for hAMSC-based DDS in oncotheranostics. Full article
(This article belongs to the Special Issue Stem Cell Biology in Health and Disease)
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11 pages, 15851 KiB  
Article
Stem Cell Therapy Enhances Motor Activity of Triceps Surae Muscle in Mice with Hereditary Peripheral Neuropathy
by Iryna Govbakh, Vitalii Kyryk, Alina Ustymenko, Volodymyr Rubtsov, Oleg Tsupykov, Nataliya V. Bulgakova, Danylo O. Zavodovskiy, Inna Sokolowska and Andriy Maznychenko
Int. J. Mol. Sci. 2021, 22(21), 12026; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222112026 - 06 Nov 2021
Cited by 4 | Viewed by 2261
Abstract
Impaired motor and sensory functions are the main features of Charcot–Marie–Tooth disease. Mesenchymal stem cell (MSCs) therapy is one of the possible treatments for this disease. It was assumed that MSCs therapy can improve the contractile properties of the triceps surae (TS) muscles [...] Read more.
Impaired motor and sensory functions are the main features of Charcot–Marie–Tooth disease. Mesenchymal stem cell (MSCs) therapy is one of the possible treatments for this disease. It was assumed that MSCs therapy can improve the contractile properties of the triceps surae (TS) muscles in mice with hereditary peripheral neuropathy. Murine adipose-derived mesenchymal stromal cells (AD-MSCs) were obtained for transplantation into TS muscles of FVB-C-Tg(GFPU)5Nagy/J mice. Three months after AD-MSCs transplantation, animals were subjected to electrophysiological investigations. Parameters of TS muscle tension after intermittent high frequency electrical sciatic nerve stimulations were analyzed. It was found that force of TS muscle tension contraction in animals after AD-MSCs treatment was two-time higher than in untreated mice. Normalized values of force muscle contraction in different phases of electrical stimulation were 0.3 ± 0.01 vs. 0.18 ± 0.01 and 0.26 ± 0.03 vs. 0.13 ± 0.03 for treated and untreated animals, respectively. It is assumed that the two-fold increase in TS muscle strength was caused by stem cell therapy. Apparently, AD-MSCs therapy can promote nerve regeneration and partial restoration of muscle function, and thus can be a potential therapeutic agent for the treatment of peripheral neuropathies. Full article
(This article belongs to the Special Issue Stem Cell Biology in Health and Disease)
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Review

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37 pages, 2323 KiB  
Review
Perivascular Mesenchymal Stem/Stromal Cells, an Immune Privileged Niche for Viruses?
by Grégorie Lebeau, Franck Ah-Pine, Matthieu Daniel, Yosra Bedoui, Damien Vagner, Etienne Frumence and Philippe Gasque
Int. J. Mol. Sci. 2022, 23(14), 8038; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23148038 - 21 Jul 2022
Cited by 6 | Viewed by 3941
Abstract
Mesenchymal stem cells (MSCs) play a critical role in response to stress such as infection. They initiate the removal of cell debris, exert major immunoregulatory activities, control pathogens, and lead to a remodeling/scarring phase. Thus, host-derived ‘danger’ factors released from damaged/infected cells (called [...] Read more.
Mesenchymal stem cells (MSCs) play a critical role in response to stress such as infection. They initiate the removal of cell debris, exert major immunoregulatory activities, control pathogens, and lead to a remodeling/scarring phase. Thus, host-derived ‘danger’ factors released from damaged/infected cells (called alarmins, e.g., HMGB1, ATP, DNA) as well as pathogen-associated molecular patterns (LPS, single strand RNA) can activate MSCs located in the parenchyma and around vessels to upregulate the expression of growth factors and chemoattractant molecules that influence immune cell recruitment and stem cell mobilization. MSC, in an ultimate contribution to tissue repair, may also directly trans- or de-differentiate into specific cellular phenotypes such as osteoblasts, chondrocytes, lipofibroblasts, myofibroblasts, Schwann cells, and they may somehow recapitulate their neural crest embryonic origin. Failure to terminate such repair processes induces pathological scarring, termed fibrosis, or vascular calcification. Interestingly, many viruses and particularly those associated to chronic infection and inflammation may hijack and polarize MSC’s immune regulatory activities. Several reports argue that MSC may constitute immune privileged sanctuaries for viruses and contributing to long-lasting effects posing infectious challenges, such as viruses rebounding in immunocompromised patients or following regenerative medicine therapies using MSC. We will herein review the capacity of several viruses not only to infect but also to polarize directly or indirectly the functions of MSC (immunoregulation, differentiation potential, and tissue repair) in clinical settings. Full article
(This article belongs to the Special Issue Stem Cell Biology in Health and Disease)
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