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Stem Cells Aging

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (30 December 2020) | Viewed by 26176

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Centre National de la Recherche Scientifique (CNRS), Equipe de Recherche Labellisée 7001, LNOX "Leukemic Niche and Redox Metabolism," Tours, France
Interests: Mesenchymal stromal stem cell

Special Issue Information

Adult stem cells have the ability to self-renew and differentiate into various mature cells. The aging process can have deleterious effects on stem cells, decreasing their capacity for self-renewal and differentiation. The disturbances induced by the aging of stem cells are implicated in the pathophysiology of the various diseases associated with aging. It is essential to decipher the biological specificities of aged stem cells and the role of the aging process in the deterioration of stem cell function, not only to understand the pathophysiology of the pathologies of aging, but also for the future development of new therapeutic strategies to treat diseases associated with aging.

This Special Issue aims to report the latest biological knowledge on physiological aging, and to propose mechanisms associated with the pathophysiology of age-related diseases. We invite the submission of research articles, reviews, or technological reports aimed at analyzing the biological characteristics of aged cells.

Dr. Olivier Herault

Guest Editor



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Published Papers (5 papers)

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Research

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15 pages, 1333 KiB  
Article
Functional Comparison between VP64-dCas9-VP64 and dCas9-VP192 CRISPR Activators in Human Embryonic Kidney Cells
by Nasir Javaid, Thuong L. H. Pham and Sangdun Choi
Int. J. Mol. Sci. 2021, 22(1), 397; https://doi.org/10.3390/ijms22010397 - 1 Jan 2021
Cited by 5 | Viewed by 4539
Abstract
Reversal in the transcriptional status of desired genes has been exploited for multiple research, therapeutic, and biotechnological purposes. CRISPR/dCas9-based activators can activate transcriptionally silenced genes after being guided by gene-specific gRNA(s). Here, we performed a functional comparison between two such activators, VP64-dCas9-VP64 and [...] Read more.
Reversal in the transcriptional status of desired genes has been exploited for multiple research, therapeutic, and biotechnological purposes. CRISPR/dCas9-based activators can activate transcriptionally silenced genes after being guided by gene-specific gRNA(s). Here, we performed a functional comparison between two such activators, VP64-dCas9-VP64 and dCas9-VP192, in human embryonic kidney cells by the concomitant targeting of POU5F1 and SOX2. We found 22- and 6-fold upregulations in the mRNA level of POU5F1 by dCas9-VP192 and VP64-dCas9-VP64, respectively. Likewise, SOX2 was up-regulated 4- and 2-fold using dCas9-VP192 and VP64dCas9VP64, respectively. For the POU5F1 protein level, we observed 3.7- and 2.2-fold increases with dCas9-VP192 and VP64-dCas9-VP64, respectively. Similarly, the SOX2 expression was 2.4- and 2-fold higher with dCas9-VP192 and VP64-dCas9-VP64, respectively. We also confirmed that activation only happened upon co-transfecting an activator plasmid with multiplex gRNA plasmid with a high specificity to the reference genes. Our data revealed that dCas9-VP192 is more efficient than VP64-dCas9-VP64 for activating reference genes. Full article
(This article belongs to the Special Issue Stem Cells Aging)
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40 pages, 10255 KiB  
Article
Hydrogen Sulfide Modulates Adult and Reparative Neurogenesis in the Cerebellum of Juvenile Masu Salmon, Oncorhynchus masou
by Evgeniya V. Pushchina, Maria E. Stukaneva and Anatoly A. Varaksin
Int. J. Mol. Sci. 2020, 21(24), 9638; https://doi.org/10.3390/ijms21249638 - 17 Dec 2020
Cited by 11 | Viewed by 2477
Abstract
Fish are a convenient model for the study of reparative and post-traumatic processes of central nervous system (CNS) recovery, because the formation of new cells in their CNS continues throughout life. After a traumatic injury to the cerebellum of juvenile masu salmon, Oncorhynchus [...] Read more.
Fish are a convenient model for the study of reparative and post-traumatic processes of central nervous system (CNS) recovery, because the formation of new cells in their CNS continues throughout life. After a traumatic injury to the cerebellum of juvenile masu salmon, Oncorhynchus masou, the cell composition of the neurogenic zones containing neural stem cells (NSCs)/neural progenitor cells (NPCs) in the acute period (two days post-injury) changes. The presence of neuroepithelial (NE) and radial glial (RG) neuronal precursors located in the dorsal, lateral, and basal zones of the cerebellar body was shown by the immunohistochemical (IHC) labeling of glutamine synthetase (GS). Progenitors of both types are sources of neurons in the cerebellum of juvenile O. masou during constitutive growth, thus, playing an important role in CNS homeostasis and neuronal plasticity during ontogenesis. Precursors with the RG phenotype were found in the same regions of the molecular layer as part of heterogeneous constitutive neurogenic niches. The presence of neuroepithelial and radial glia GS+ cells indicates a certain proportion of embryonic and adult progenitors and, obviously, different contributions of these cells to constitutive and reparative neurogenesis in the acute post-traumatic period. Expression of nestin and vimentin was revealed in neuroepithelial cerebellar progenitors of juvenile O. masou. Patterns of granular expression of these markers were found in neurogenic niches and adjacent areas, which probably indicates the neurotrophic and proneurogenic effects of vimentin and nestin in constitutive and post-traumatic neurogenesis and a high level of constructive metabolism. No expression of vimentin and nestin was detected in the cerebellar RG of juvenile O. masou. Thus, the molecular markers of NSCs/NPCs in the cerebellum of juvenile O. masou are as follows: vimentin, nestin, and glutamine synthetase label NE cells in intact animals and in the post-traumatic period, while GS expression is present in the RG of intact animals and decreases in the acute post-traumatic period. A study of distribution of cystathionine β-synthase (CBS) in the cerebellum of intact young O. masou showed the expression of the marker mainly in type 1 cells, corresponding to NSCs/NCPs for other molecular markers. In the post-traumatic period, the number of CBS+ cells sharply increased, which indicates the involvement of H2S in the post-traumatic response. Induction of CBS in type 3 cells indicates the involvement of H2S in the metabolism of extracellular glutamate in the cerebellum, a decrease in the production of reactive oxygen species, and also arrest of the oxidative stress development, a weakening of the toxic effects of glutamate, and a reduction in excitotoxicity. The obtained results allow us to consider H2S as a biologically active substance, the numerous known effects of which can be supplemented by participation in the processes of constitutive neurogenesis and neuronal regeneration. Full article
(This article belongs to the Special Issue Stem Cells Aging)
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19 pages, 4776 KiB  
Article
Age, Diet and Epidermal Signaling Modulate Dermal Fibroblasts’ Adipogenic Potential
by Katarzyna Walendzik, Joanna Bukowska, Marta Kopcewicz, Sylwia Machcinska, Jeffrey M. Gimble and Barbara Gawronska-Kozak
Int. J. Mol. Sci. 2020, 21(23), 8955; https://doi.org/10.3390/ijms21238955 - 25 Nov 2020
Cited by 5 | Viewed by 2527
Abstract
The recognition of a distinct fat depot, the dermal white adipose tissue (dWAT), points out the complexity of the interaction among skin resident cells: keratinocytes, dermal fibroblasts (DFs) and adipocytes in response to physiological (diet, age) and pathological (injury) stimulations. dWAT has been [...] Read more.
The recognition of a distinct fat depot, the dermal white adipose tissue (dWAT), points out the complexity of the interaction among skin resident cells: keratinocytes, dermal fibroblasts (DFs) and adipocytes in response to physiological (diet, age) and pathological (injury) stimulations. dWAT has been recognized as a significant contributor to thermoregulation, hair cycle, immune response, wound healing and scarring. In this study, we examined age- and diet-related changes in dWAT modulation and DFs’ adipogenic potential. The data showed that diet modulates dWAT expansion predominantly by hypertrophy, whereas age affects the pool of adipocyte progenitor cells in the skin indicating its role in dWAT hyperplasia. Analysis of DFs’ migratory abilities in the model of skin explants isolated from the skin of young, old, low (LFD)- or high (HFD)-fat diet C56BL/6 mice revealed that HFD, regardless of animal age has the most profound stimulatory impact of DF migration. We determined that the adipogenic potential of DFs is comparable to stromal vascular fraction (SVF) of inguinal fat depot and ear mesenchymal stem cells (EMSC). We also showed the stimulatory role of epidermally expressed transcription factor Foxn1 on adipogenic signaling: bone morphogenetic protein 2 (Bmp2) and insulin-like growth factor 2 (Igf2) in keratinocytes. Full article
(This article belongs to the Special Issue Stem Cells Aging)
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Review

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21 pages, 2495 KiB  
Review
Reprogramming: Emerging Strategies to Rejuvenate Aging Cells and Tissues
by Quentin Alle, Enora Le Borgne, Ollivier Milhavet and Jean-Marc Lemaitre
Int. J. Mol. Sci. 2021, 22(8), 3990; https://doi.org/10.3390/ijms22083990 - 13 Apr 2021
Cited by 22 | Viewed by 12587
Abstract
Aging is associated with a progressive and functional decline of all tissues and a striking increase in many “age-related diseases”. Although aging has long been considered an inevitable process, strategies to delay and potentially even reverse the aging process have recently been developed. [...] Read more.
Aging is associated with a progressive and functional decline of all tissues and a striking increase in many “age-related diseases”. Although aging has long been considered an inevitable process, strategies to delay and potentially even reverse the aging process have recently been developed. Here, we review emerging rejuvenation strategies that are based on reprogramming toward pluripotency. Some of these approaches may eventually lead to medical applications to improve healthspan and longevity. Full article
(This article belongs to the Special Issue Stem Cells Aging)
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26 pages, 642 KiB  
Review
“Empowering” Cardiac Cells via Stem Cell Derived Mitochondrial Transplantation- Does Age Matter?
by Matthias Mietsch and Rabea Hinkel
Int. J. Mol. Sci. 2021, 22(4), 1824; https://doi.org/10.3390/ijms22041824 - 12 Feb 2021
Cited by 4 | Viewed by 3525
Abstract
With cardiovascular diseases affecting millions of patients, new treatment strategies are urgently needed. The use of stem cell based approaches has been investigated during the last decades and promising effects have been achieved. However, the beneficial effect of stem cells has been found [...] Read more.
With cardiovascular diseases affecting millions of patients, new treatment strategies are urgently needed. The use of stem cell based approaches has been investigated during the last decades and promising effects have been achieved. However, the beneficial effect of stem cells has been found to being partly due to paracrine functions by alterations of their microenvironment and so an interesting field of research, the “stem- less” approaches has emerged over the last years using or altering the microenvironment, for example, via deletion of senescent cells, application of micro RNAs or by modifying the cellular energy metabolism via targeting mitochondria. Using autologous muscle-derived mitochondria for transplantations into the affected tissues has resulted in promising reports of improvements of cardiac functions in vitro and in vivo. However, since the targeted treatment group represents mainly elderly or otherwise sick patients, it is unclear whether and to what extent autologous mitochondria would exert their beneficial effects in these cases. Stem cells might represent better sources for mitochondria and could enhance the effect of mitochondrial transplantations. Therefore in this review we aim to provide an overview on aging effects of stem cells and mitochondria which might be important for mitochondrial transplantation and to give an overview on the current state in this field together with considerations worthwhile for further investigations. Full article
(This article belongs to the Special Issue Stem Cells Aging)
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