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Adult Stem Cells in Aging
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Adult Stem Cells in Aging

A special issue of Journal of Personalized Medicine (ISSN 2075-4426). This special issue belongs to the section "Clinical Medicine, Cell, and Organism Physiology".

Deadline for manuscript submissions: closed (10 March 2022) | Viewed by 25005

Special Issue Editor

Dr. Drenka Trivanovic

E-Mail Website
Guest Editor
Group for Hematology and Stem Cells, Institute for Medical Research, National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia
Interests: stem cells; bone marrow adipose tissue; cancer
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Unrelenting cellular process of aging is a basic part of the physiological fading of longevity. Dysregulation of aged-cell functions is genetically and epigenetically regulated and this is described in many organisms, from yeast to mammals. Furthermore, aging is often associated with loss of skin elasticity, adipose tissue accumulation, atherosclerosis, immune system failures, bones fragility, and cancer.

Aging program coincides with cell fate decision to either continue or abandon regular maintenance processes. The molecular hallmarks of aging involve the aberrant metabolic phenotype, cytoskeleton, mitochondrial function and cell signaling, directly affecting cell redox environment and divisions, senescence and cell death program. From the “stem cell-centric” point of view, it can be speculated whether stem cell age and if so, how the aging process varies in different tissues (e.g. hematopoietic, vascular, bones, adipose, neural…). It has been indicated that stem cell number and self-renewal does not necessarily decline with aging, but their functions — the capacity to produce progenitors and differentiated cells appears to be reduced. Moreover, the recent findings suggest that achievement and maintenance of the stem cell profile have an important role in close interaction between aging and carcinogenesis. One of the goals of this this Special Issue is to discuss the lack of appropriate tools to test the function of stem cells, which made it difficult to determine if a decline in stem-cell function is indeed a cause of the degradation of the regenerative/homeostatic capacities that is seen in many aged tissues.   

This Special Issue on “Adult Stem Cells in Aging” encourages Authors to submit their original research or review articles that bring new evidences or synthesis of the most recent and breakthrough data in the field of stem cell behavior in aging process. Topics include, but are not limited to:

 Aged stem cell phenotype: nuclear organization, transcriptional and translational regulation

  • Aged stem cell niche components; stem cells in physiological and pathologic aging
  • Tumor-suppressor molecules in regulation of cellular senescence
  • Molecular interactions of cellular quiescence, aging, programmed death/autophagy and cancer
  • Mitochondrial health and epigenetic alternations during aging in quiescent and activated stem cells
  • Resistance of stem cells to pro-aging agents and rejuvenation approaches (e.g. nutrient limitation, senescence modulators)
  • Diseased stem cell phenotypes and clinical relevance of delayed aging

Dr. Drenka Trivanovic
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. Journal of Personalized Medicine 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 2600 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 cells
  • aging
  • quiescence
  • mitochondria
  • differentiation
  • cancer
  • cell death

Published Papers (7 papers)

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Editorial

Jump to: Research, Review

2 pages, 172 KiB  
Editorial
Adult Stem Cells in Aging
by Drenka Trivanović
J. Pers. Med. 2022, 12(5), 795; https://doi.org/10.3390/jpm12050795 - 14 May 2022
Cited by 1 | Viewed by 1413
Abstract
Aging process is associated with numerous intrinsic and extrinsic factors that contribute to the adipose tissue accumulation, atherosclerosis, immune system failures, bone fragility, and cancer [...] Full article
(This article belongs to the Special Issue Adult Stem Cells in Aging)

Research

Jump to: Editorial, Review

15 pages, 2530 KiB  
Article
Hydroxyurea Induces Bone Marrow Mesenchymal Stromal Cells Senescence and Modifies Cell Functionality In Vitro
by Sunčica Kapor, Milica Vukotić, Tijana Subotički, Dragoslava Đikić, Olivera Mitrović Ajtić, Milica Radojković, Vladan P. Čokić and Juan F. Santibanez
J. Pers. Med. 2021, 11(11), 1048; https://doi.org/10.3390/jpm11111048 - 20 Oct 2021
Cited by 3 | Viewed by 2331
Abstract
Hydroxyurea (HU) is an antineoplastic agent that functions as an antimetabolite compound by inhibiting the ribonucleotide reductase. HU acts mainly as a cytostatic drug that through DNA replication stress may trigger a premature senescence-like cell phenotype, though its influence on bone marrow-derived mesenchymal [...] Read more.
Hydroxyurea (HU) is an antineoplastic agent that functions as an antimetabolite compound by inhibiting the ribonucleotide reductase. HU acts mainly as a cytostatic drug that through DNA replication stress may trigger a premature senescence-like cell phenotype, though its influence on bone marrow-derived mesenchymal stem/stromal cell (BMMSC) functions has not elucidated yet. Our results indicate that HU inhibits the growth of human BMMSC alongside senescence-like changes in both morphology and replicative potential, provokes cell cycle arrest at the S phase without affecting cellular viability and induces the expression of senescence-associated β-galactosidase and p16INK4. Moreover, HU-induced senescent BMMSC, although they did not change MSC markers expression, exhibited reduced capacity osteogenic and adipogenic differentiation. Conversely, HU treatment increased immunoregulatory functions of BMMSC compared with untreated cells and determined by T-cell proliferation. Interestingly, HU did not influence the capacity of BMMSC to induce monocytic myeloid-derived suppressor cells. Thus, these results suggest that HU improves the BMMSC functions on the T-cell inhibition and preserves their interaction with myeloid cell compartment. Mechanistically, BMMSC under HU treatment displayed a downregulation of mTOR and p38 MAPK signaling that may explain the reduced cell differentiation and increased immunomodulation activities. Together, the results obtained in this investigation suggest that HU by inducing senescence-like phenotype of BMMSC influences their cellular differentiation and immunoregulatory functions. Full article
(This article belongs to the Special Issue Adult Stem Cells in Aging)
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Review

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30 pages, 1266 KiB  
Review
Bone Marrow Aging and the Leukaemia-Induced Senescence of Mesenchymal Stem/Stromal Cells: Exploring Similarities
by Paola Fernanda Ruiz-Aparicio and Jean-Paul Vernot
J. Pers. Med. 2022, 12(5), 716; https://doi.org/10.3390/jpm12050716 - 29 Apr 2022
Cited by 8 | Viewed by 2993
Abstract
Bone marrow aging is associated with multiple cellular dysfunctions, including perturbed haematopoiesis, the propensity to haematological transformation, and the maintenance of leukaemia. It has been shown that instructive signals from different leukemic cells are delivered to stromal cells to remodel the bone marrow [...] Read more.
Bone marrow aging is associated with multiple cellular dysfunctions, including perturbed haematopoiesis, the propensity to haematological transformation, and the maintenance of leukaemia. It has been shown that instructive signals from different leukemic cells are delivered to stromal cells to remodel the bone marrow into a supportive leukemic niche. In particular, cellular senescence, a physiological program with both beneficial and deleterious effects on the health of the organisms, may be responsible for the increased incidence of haematological malignancies in the elderly and for the survival of diverse leukemic cells. Here, we will review the connection between BM aging and cellular senescence and the role that these processes play in leukaemia progression. Specifically, we discuss the role of mesenchymal stem cells as a central component of the supportive niche. Due to the specificity of the genetic defects present in leukaemia, one would think that bone marrow alterations would also have particular changes, making it difficult to envisage a shared therapeutic use. We have tried to summarize the coincident features present in BM stromal cells during aging and senescence and in two different leukaemias, acute myeloid leukaemia, with high frequency in the elderly, and B-acute lymphoblastic leukaemia, mainly a childhood disease. We propose that mesenchymal stem cells are similarly affected in these different leukaemias, and that the changes that we observed in terms of cellular function, redox balance, genetics and epigenetics, soluble factor repertoire and stemness are equivalent to those occurring during BM aging and cellular senescence. These coincident features may be used to explore strategies useful to treat various haematological malignancies. Full article
(This article belongs to the Special Issue Adult Stem Cells in Aging)
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18 pages, 1049 KiB  
Review
Adipose-Derived Stem Cells for Facial Rejuvenation
by Agnieszka Surowiecka and Jerzy Strużyna
J. Pers. Med. 2022, 12(1), 117; https://doi.org/10.3390/jpm12010117 - 16 Jan 2022
Cited by 19 | Viewed by 6983
Abstract
The interest in regenerative medicine is increasing, and it is a dynamically developing branch of aesthetic surgery. Biocompatible and autologous-derived products such as platelet-rich plasma or adult mesenchymal stem cells are often used for aesthetic purposes. Their application originates from wound healing and [...] Read more.
The interest in regenerative medicine is increasing, and it is a dynamically developing branch of aesthetic surgery. Biocompatible and autologous-derived products such as platelet-rich plasma or adult mesenchymal stem cells are often used for aesthetic purposes. Their application originates from wound healing and orthopaedics. Adipose-derived stem cells are a powerful agent in skin rejuvenation. They secrete growth factors and anti-inflammatory cytokines, stimulate tissue regeneration by promoting the secretion of extracellular proteins and secrete antioxidants that neutralize free radicals. In an office procedure, without cell incubation and counting, the obtained product is stromal vascular fraction, which consists of not only stem cells but also other numerous active cells such as pericytes, preadipocytes, immune cells, and extra-cellular matrix. Adipose-derived stem cells, when injected into dermis, improved skin density and overall skin appearance, and increased skin hydration and number of capillary vessels. The main limitation of mesenchymal stem cell transfers is the survival of the graft. The final outcomes are dependent on many factors, including the age of the patient, technique of fat tissue harvesting, technique of lipoaspirate preparation, and technique of fat graft injection. It is very difficult to compare available studies because of the differences and multitude of techniques used. Fat harvesting is associated with potentially life-threatening complications, such as massive bleeding, embolism, or clots. However, most of the side effects are mild and transient: primarily hematomas, oedema, and mild pain. Mesenchymal stem cells that do not proliferate when injected into dermis promote neoangiogenesis, that is why respectful caution should be taken in the case of oncologic patients. A longer clinical observation on a higher number of participants should be performed to develop reliable indications and guidelines for transferring ADSCs. Full article
(This article belongs to the Special Issue Adult Stem Cells in Aging)
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19 pages, 841 KiB  
Review
Tumorigenic Aspects of MSC Senescence—Implication in Cancer Development and Therapy
by Slavko Mojsilović, Aleksandra Jauković, Tamara Kukolj, Hristina Obradović, Ivana Okić Đorđević, Anđelija Petrović and Diana Bugarski
J. Pers. Med. 2021, 11(11), 1133; https://doi.org/10.3390/jpm11111133 - 2 Nov 2021
Cited by 9 | Viewed by 2494
Abstract
As an organism ages, many physiological processes change, including the immune system. This process, called immunosenescence, characterized by abnormal activation and imbalance of innate and adaptive immunity, leads to a state of chronic low-grade systemic inflammation, termed inflammaging. Aging and inflammaging are considered [...] Read more.
As an organism ages, many physiological processes change, including the immune system. This process, called immunosenescence, characterized by abnormal activation and imbalance of innate and adaptive immunity, leads to a state of chronic low-grade systemic inflammation, termed inflammaging. Aging and inflammaging are considered to be the root of many diseases of the elderly, as infections, autoimmune and chronic inflammatory diseases, degenerative diseases, and cancer. The role of mesenchymal stromal/stem cells (MSCs) in the inflammaging process and the age-related diseases is not completely established, although numerous features of aging MSCs, including altered immunomodulatory properties, impeded MSC niche supporting functions, and senescent MSC secretory repertoire are consistent with inflammaging development. Although senescence has its physiological function and can represent a mechanism of tumor prevention, in most cases it eventually transforms into a deleterious (para-)inflammatory process that promotes tumor growth. In this review we are going through current literature, trying to explore the role of senescent MSCs in making and/or sustaining a microenvironment permissive to tumor development and to analyze the therapeutic options that could target this process. Full article
(This article belongs to the Special Issue Adult Stem Cells in Aging)
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26 pages, 459 KiB  
Review
Epigenetic Clock and Circadian Rhythms in Stem Cell Aging and Rejuvenation
by Ekaterina M. Samoilova, Vladimir V. Belopasov, Evgenia V. Ekusheva, Chao Zhang, Alexander V. Troitskiy and Vladimir P. Baklaushev
J. Pers. Med. 2021, 11(11), 1050; https://doi.org/10.3390/jpm11111050 - 20 Oct 2021
Cited by 12 | Viewed by 4431
Abstract
This review summarizes the current understanding of the interaction between circadian rhythms of gene expression and epigenetic clocks characterized by the specific profile of DNA methylation in CpG-islands which mirror the senescence of all somatic cells and stem cells in particular. Basic mechanisms [...] Read more.
This review summarizes the current understanding of the interaction between circadian rhythms of gene expression and epigenetic clocks characterized by the specific profile of DNA methylation in CpG-islands which mirror the senescence of all somatic cells and stem cells in particular. Basic mechanisms of regulation for circadian genes CLOCK-BMAL1 as well as downstream clock-controlled genes (ССG) are also discussed here. It has been shown that circadian rhythms operate by the finely tuned regulation of transcription and rely on various epigenetic mechanisms including the activation of enhancers/suppressors, acetylation/deacetylation of histones and other proteins as well as DNA methylation. Overall, up to 20% of all genes expressed by the cell are subject to expression oscillations associated with circadian rhythms. Additionally included in the review is a brief list of genes involved in the regulation of circadian rhythms, along with genes important for cell aging, and oncogenesis. Eliminating some of them (for example, Sirt1) accelerates the aging process, while the overexpression of Sirt1, on the contrary, protects against age-related changes. Circadian regulators control a number of genes that activate the cell cycle (Wee1, c-Myc, p20, p21, and Cyclin D1) and regulate histone modification and DNA methylation. Approaches for determining the epigenetic age from methylation profiles across CpG islands in individual cells are described. DNA methylation, which characterizes the function of the epigenetic clock, appears to link together such key biological processes as regeneration and functioning of stem cells, aging and malignant transformation. Finally, the main features of adult stem cell aging in stem cell niches and current possibilities for modulating the epigenetic clock and stem cells rejuvenation as part of antiaging therapy are discussed. Full article
(This article belongs to the Special Issue Adult Stem Cells in Aging)
15 pages, 687 KiB  
Review
Cell and Cell-Free Therapies to Counteract Human Premature and Physiological Aging: MSCs Come to Light
by Arantza Infante and Clara I. Rodríguez
J. Pers. Med. 2021, 11(10), 1043; https://doi.org/10.3390/jpm11101043 - 18 Oct 2021
Cited by 10 | Viewed by 2462
Abstract
The progressive loss of the regenerative potential of tissues is one of the most obvious consequences of aging, driven by altered intercellular communication, cell senescence and niche-specific stem cell exhaustion, among other drivers. Mesenchymal tissues, such as bone, cartilage and fat, which originate [...] Read more.
The progressive loss of the regenerative potential of tissues is one of the most obvious consequences of aging, driven by altered intercellular communication, cell senescence and niche-specific stem cell exhaustion, among other drivers. Mesenchymal tissues, such as bone, cartilage and fat, which originate from mesenchymal stem cell (MSC) differentiation, are especially affected by aging. Senescent MSCs show limited proliferative capacity and impairment in key defining features: their multipotent differentiation and secretory abilities, leading to diminished function and deleterious consequences for tissue homeostasis. In the past few years, several interventions to improve human healthspan by counteracting the cellular and molecular consequences of aging have moved closer to the clinic. Taking into account the MSC exhaustion occurring in aging, advanced therapies based on the potential use of young allogeneic MSCs and derivatives, such as extracellular vesicles (EVs), are gaining attention. Based on encouraging pre-clinical and clinical data, this review assesses the strong potential of MSC-based (cell and cell-free) therapies to counteract age-related consequences in both physiological and premature aging scenarios. We also discuss the mechanisms of action of these therapies and the possibility of enhancing their clinical potential by exposing MSCs to niche-relevant signals. Full article
(This article belongs to the Special Issue Adult Stem Cells in Aging)
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