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Escarrer-Garau G, Martín-Medina A, Truyols-Vives J, Gómez-Bellvert C, Elowsson L, Westergren-Thorsson G, Molina-Molina M, Mercader-Barceló J, Sala-Llinàs E. In Vivo and In Vitro Pro-Fibrotic Response of Lung-Resident Mesenchymal Stem Cells from Patients with Idiopathic Pulmonary Fibrosis. Cells 2024; 13:160. [PMID: 38247851 PMCID: PMC10814068 DOI: 10.3390/cells13020160] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2023] [Revised: 01/05/2024] [Accepted: 01/09/2024] [Indexed: 01/23/2024] Open
Abstract
Lung-resident mesenchymal stem cells (LR-MSC) are thought to participate in idiopathic pulmonary fibrosis (IPF) by differentiating into myofibroblasts. On the other hand, LR-MSC in IPF patients present senescence-related features. It is unclear how they respond to a profibrotic environment. Here, we investigated the profibrotic response of LR-MSC isolated from IPF and control (CON) patients. LR-MSC were inoculated in mice 48 h after bleomycin (BLM) instillation to analyze their contribution to lung damage. In vitro, LR-MSC were exposed to TGFβ. Mice inoculated with IPF LR-MSC exhibited worse maintenance of their body weight. The instillation of either IPF or CON LR-MSC sustained BLM-induced histological lung damage, bronchoalveolar lavage fluid cell count, and the expression of the myofibroblast marker, extracellular matrix (ECM) proteins, and proinflammatory cytokines in the lungs. In vitro, IPF LR-MSC displayed higher basal protein levels of aSMA and fibronectin than CON LR-MSC. However, the TGFβ response in the expression of TGFβ, aSMA, and ECM genes was attenuated in IPF LR-MSC. In conclusion, IPF LR-MSC have acquired myofibroblastic features, but their capacity to further respond to profibrotic stimuli seems to be attenuated. In an advanced stage of the disease, LR-MSC may participate in disease progression owing to their limited ability to repair epithelial damage.
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Affiliation(s)
| | - Aina Martín-Medina
- iRESPIRE Research Group, Health Research Institute of the Balearic Islands (IdISBa), 07120 Palma, Spain
| | - Joan Truyols-Vives
- MolONE Research Group, University of the Balearic Islands (UIB), 07122 Palma, Spain
| | | | - Linda Elowsson
- Lung Biology, Department of Experimental Medical Science, Lund University, 08908 Lund, Sweden
| | | | - Maria Molina-Molina
- ILD Unit, Respiratory Department, University Hospital of Bellvitge-Bellvitge Biomedical Research Institute (IDIBELL), 08908 Hospitalet de Llobregat, Barcelona, Spain
- Centre of Biomedical Research Network in Respiratory Diseases (CIBERES), 28029 Madrid, Spain
| | - Josep Mercader-Barceló
- MolONE Research Group, University of the Balearic Islands (UIB), 07122 Palma, Spain
- iRESPIRE Research Group, Health Research Institute of the Balearic Islands (IdISBa), 07120 Palma, Spain
- Centre of Biomedical Research Network in Respiratory Diseases (CIBERES), 28029 Madrid, Spain
| | - Ernest Sala-Llinàs
- iRESPIRE Research Group, Health Research Institute of the Balearic Islands (IdISBa), 07120 Palma, Spain
- Centre of Biomedical Research Network in Respiratory Diseases (CIBERES), 28029 Madrid, Spain
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2
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Mercader-Barceló J, Martín-Medina A, Truyols-Vives J, Escarrer-Garau G, Elowsson L, Montes-Worboys A, Río-Bocos C, Muncunill-Farreny J, Velasco-Roca J, Cederberg A, Kadefors M, Molina-Molina M, Westergren-Thorsson G, Sala-Llinàs E. Mitochondrial Dysfunction in Lung Resident Mesenchymal Stem Cells from Idiopathic Pulmonary Fibrosis Patients. Cells 2023; 12:2084. [PMID: 37626894 PMCID: PMC10453747 DOI: 10.3390/cells12162084] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2023] [Revised: 08/09/2023] [Accepted: 08/13/2023] [Indexed: 08/27/2023] Open
Abstract
Idiopathic pulmonary fibrosis (IPF) is characterized by an aberrant repair response with uncontrolled turnover of extracellular matrix involving mesenchymal cell phenotypes, where lung resident mesenchymal stem cells (LRMSC) have been supposed to have an important role. However, the contribution of LRMSC in lung fibrosis is not fully understood, and the role of LRMSC in IPF remains to be elucidated. Here, we performed transcriptomic and functional analyses on LRMSC isolated from IPF and control patients (CON). Both over-representation and gene set enrichment analyses indicated that oxidative phosphorylation is the major dysregulated pathway in IPF LRMSC. The most relevant differences in biological processes included complement activation, mesenchyme development, and aerobic electron transport chain. Compared to CON LRMSC, IPF cells displayed impaired mitochondrial respiration, lower expression of genes involved in mitochondrial dynamics, and dysmorphic mitochondria. These changes were linked to an impaired autophagic response and a lower mRNA expression of pro-apoptotic genes. In addition, IPF TGFβ-exposed LRMSC presented different expression profiles of mitochondrial-related genes compared to CON TGFβ-treated cells, suggesting that TGFβ reinforces mitochondrial dysfunction. In conclusion, these results suggest that mitochondrial dysfunction is a major event in LRMSC and that their occurrence might limit LRMSC function, thereby contributing to IPF development.
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Affiliation(s)
- Josep Mercader-Barceló
- iRESPIRE Research Group, Health Research Institute of the Balearic Islands (IdISBa), 07120 Palma, Spain
- MolONE Research Group, University of the Balearic Islands, 07122 Palma, Spain
| | - Aina Martín-Medina
- iRESPIRE Research Group, Health Research Institute of the Balearic Islands (IdISBa), 07120 Palma, Spain
| | - Joan Truyols-Vives
- MolONE Research Group, University of the Balearic Islands, 07122 Palma, Spain
| | | | - Linda Elowsson
- Lung Biology, Department of Experimental Medical Science, Lund University, 08908 Lund, Sweden
| | - Ana Montes-Worboys
- ILD Unit, Respiratory Department, University Hospital of Bellvitge-Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, 08908 Barcelona, Spain
| | - Carlos Río-Bocos
- iRESPIRE Research Group, Health Research Institute of the Balearic Islands (IdISBa), 07120 Palma, Spain
| | | | - Julio Velasco-Roca
- Health Research Institute of the Balearic Islands (IdISBa), 07120 Palma, Spain
| | - Anna Cederberg
- Lung Biology, Department of Experimental Medical Science, Lund University, 08908 Lund, Sweden
| | - Måns Kadefors
- Lung Biology, Department of Experimental Medical Science, Lund University, 08908 Lund, Sweden
| | - Maria Molina-Molina
- ILD Unit, Respiratory Department, University Hospital of Bellvitge-Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, 08908 Barcelona, Spain
- Centre of Biomedical Research Network in Respiratory Diseases (CIBERES), 28029 Madrid, Spain
| | | | - Ernest Sala-Llinàs
- iRESPIRE Research Group, Health Research Institute of the Balearic Islands (IdISBa), 07120 Palma, Spain
- Centre of Biomedical Research Network in Respiratory Diseases (CIBERES), 28029 Madrid, Spain
- Respiratory Department, Son Espases University Hospital, 07120 Palma, Spain
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Di Vincenzo M, Orciani M. Special Issue "The Role of Mesenchymal Stem Cells on Inflammatory and Fibrotic Diseases". Int J Mol Sci 2023; 24:ijms24108578. [PMID: 37239925 DOI: 10.3390/ijms24108578] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2023] [Revised: 05/09/2023] [Accepted: 05/10/2023] [Indexed: 05/28/2023] Open
Abstract
This Special Issue focused on the complex role played by MSCs in the onset and development of inflammatory diseases: MSCs can support or counteract inflammation and, in turn, the onset of disease [...].
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Affiliation(s)
- Mariangela Di Vincenzo
- Department of Clinical and Molecular Sciences-Histology, Università Politecnica delle Marche, 60126 Ancona, Italy
| | - Monia Orciani
- Department of Clinical and Molecular Sciences-Histology, Università Politecnica delle Marche, 60126 Ancona, Italy
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4
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Di Vincenzo M, Diotallevi F, Piccirillo S, Carnevale G, Offidani A, Campanati A, Orciani M. miRNAs, Mesenchymal Stromal Cells and Major Neoplastic and Inflammatory Skin Diseases: A Page Being Written: A Systematic Review. Int J Mol Sci 2023; 24:ijms24108502. [PMID: 37239847 DOI: 10.3390/ijms24108502] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2023] [Revised: 03/31/2023] [Accepted: 04/04/2023] [Indexed: 05/28/2023] Open
Abstract
Micro RNAs (miRNAs) are a type of non-coding RNA (ncRNA) and typically interact with specific target mRNAs through complementary base pairing, affecting their translation and/or stability. MiRNAs regulate nearly all cellular functions, including the cell fate of mesenchymal stromal cells (MSCs). It is now accepted that various pathologies arise at the stem level, and, in this scenario, the role played by miRNAs in the fate of MSCs becomes of primary concern. Here we have considered the existing literature in the field of miRNAs, MSCs and skin diseases, classified as inflammatory (such as psoriasis and atopic dermatitis-AD) and neoplastic (melanoma and non-melanoma-skin-cancer including squamous cell and basal cell carcinoma) diseases. In this scoping review article, the evidence recovered indicates that this topic has attracted attention, but it is still a matter of opinion. A protocol for this review was registered in PROSPERO with the registration number "CRD42023420245". According to the different skin disorders and to the specific cellular mechanisms considered (cancer stem cells, extracellular vesicles, inflammation), miRNAs may play a pro- or anti-inflammatory, as well as a tumor suppressive, or supporting, role, indicating a complex regulation of their function. It is evident that the mode of action of miRNAs is more than a switch on-off, and all the observed effects of their dysregulated expression must be checked in a detailed analysis of the targeted proteins. The involvement of miRNAs has been studied mainly for squamous cell carcinoma and melanoma, and much less in psoriasis and AD; different mechanisms have been considered, such as miRNAs included in extracellular vesicles derived both from MSCs or tumor cells, miRNAs involved in cancer stem cells formation, up to miRNAs as candidates to be new therapeutic tools.
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Affiliation(s)
- Mariangela Di Vincenzo
- Department of Clinical and Molecular Sciences-Histology, Università Politecnica delle Marche, 60126 Ancona, Italy
| | - Federico Diotallevi
- Department of Clinical and Molecular Sciences-Dermatological Clinic, Università Politecnica delle Marche, 60126 Ancona, Italy
| | - Silvia Piccirillo
- Department of Biomedical Sciences and Public Health-Pharmacology, Università Politecnica delle Marche, 60126 Ancona, Italy
| | - Gianluca Carnevale
- Department of Surgery, Medicine, Dentistry and Morphological Sciences with Interest in Transplant, Oncology and Regenerative Medicine, Università di Modena e Reggio Emilia, 41121 Modena, Italy
| | - Annamaria Offidani
- Department of Clinical and Molecular Sciences-Dermatological Clinic, Università Politecnica delle Marche, 60126 Ancona, Italy
| | - Anna Campanati
- Department of Clinical and Molecular Sciences-Dermatological Clinic, Università Politecnica delle Marche, 60126 Ancona, Italy
| | - Monia Orciani
- Department of Clinical and Molecular Sciences-Histology, Università Politecnica delle Marche, 60126 Ancona, Italy
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Fikry H, Saleh LA, Gawad SA. Therapeutic effect of adipose-derived mesenchymal stem cells (AD-MSCs) compared to pirfenidone on corticosteroid resistance in a mouse model of acute exacerbation of idiopathic pulmonary fibrosis. Histol Histopathol 2022; 37:1065-1083. [PMID: 35816024 DOI: 10.14670/hh-18-493] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
INTRODUCTION Acute exacerbation-idiopathic pulmonary fibrosis (AE-IPF) is a life-threatening condition. In the treatment of AE-IPF, corticosteroid medication is commonly utilized. However, there is insufficient evidence to justify its usage. Pirfenidone (PFD) has recently been discovered to be effective in the treatment of AE-IPF patients. However, regenerative therapy, such as stem cell therapy or tissue engineering, is necessary due to ineffective and limited therapies. Combining MSC transplantation with pharmacological therapy may also give additional benefits; nevertheless, its use must be proven experimentally. As a result, the goal of this study was to assess the therapeutic effects of adipose-derived mesenchymal stem cells (AD-MSCs) on corticosteroid resistance in an animal model of AE-IPF caused by bleomycin compared to PFD. MATERIALS AND METHODS Seventy C57BL/6J male mice were randomly divided into seven groups, control, BLM, methylprednisolone (MP), PFD, AD-MSCs, PFD +MP, and AD-MSCs +MP. RESULTS In terms of survival, collagen deposition, the acute lung injury score (ALI), and the Ashcroft score, AD-MSCs exceeded PFD. AD-MSCs + MP provided protection and preserved the lung's architecture in BLM-induced AE. In addition, AD-MSCs successfully decreased chemokine (CC motif) ligand-2 (CCL2) positive cells and lower pro-fibrotic and pro-inflammatory cytokines. CONCLUSIONS AD-MSCs enhanced histological structure, Ashcroft and ALI scores, lung collagen deposition, survival, and cytokines in an animal model of AE-IPF. As a result, we believe that AD-MSCs may be more therapeutically helpful for AE-IPF than presently available therapies, either alone or in conjunction with MP.
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Affiliation(s)
- Heba Fikry
- Department of Histology and Cell Biology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
| | - Lobna A Saleh
- Department of Clinical Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Sara Abdel Gawad
- Department of Histology and Cell Biology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
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A Possible Cause for the Differential Expression of a Subset of miRNAs in Mesenchymal Stem Cells Derived from Myometrium and Leiomyoma. Genes (Basel) 2022; 13:genes13071106. [PMID: 35885889 PMCID: PMC9319258 DOI: 10.3390/genes13071106] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Revised: 06/15/2022] [Accepted: 06/17/2022] [Indexed: 12/01/2022] Open
Abstract
The aetiology of leiomyoma is debated; however, dysregulated progenitor cells or miRNAs appear to be involved. Previous profiling analysis of miRNA in healthy myometrium- (M-MSCs) and leiomyoma- (L-MSCs) derived mesenchymal stem cells (MSCs) identified 15 miRNAs differentially expressed between M-MSCs and L-MSCs. Here, we try to elucidate whether these differentially regulated 15 miRNAs arise as a conversion of M-MSCs along the differentiation process or whether they may originate from divergent cell commitment. To trace the origin of the dysregulation, a comparison was made of the expression of miRNAs previously identified as differentially regulated in M-MSCs and L-MSCs with that detected in MSCs from amniotic fluid (considered as a substitute for embryonic cells). The results do not allow for a foregone conclusion: the miRNAs converging to the adherens junction pathway showed a gradual change along the differentiation process, and the miRNAs which coincided with the other three pathways (ECM-receptor interaction, TGFβ and cell cycle) showed a complex, not linear, regulation and, therefore, a trend along the hypothetical differentiation process was not deduced. However, the role of miRNAs appears to be predominant in the onset of leiomyoma and may follow two different mechanisms (early commitment; exacerbation); furthermore, miRNAs can support the observed (epigenetic) predisposition.
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Li C, Wang B. Mesenchymal Stem/Stromal Cells in Progressive Fibrogenic Involvement and Anti-Fibrosis Therapeutic Properties. Front Cell Dev Biol 2022; 10:902677. [PMID: 35721482 PMCID: PMC9198494 DOI: 10.3389/fcell.2022.902677] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Accepted: 05/13/2022] [Indexed: 11/22/2022] Open
Abstract
Fibrosis refers to the connective tissue deposition and stiffness usually as a result of injury. Fibrosis tissue-resident mesenchymal cells, including fibroblasts, myofibroblast, smooth muscle cells, and mesenchymal stem/stromal cells (MSCs), are major players in fibrogenic processes under certain contexts. Acknowledging differentiation potential of MSCs to the aforementioned other types of mesenchymal cell lineages is essential for better understanding of MSCs’ substantial contributions to progressive fibrogenesis. MSCs may represent a potential therapeutic option for fibrosis resolution owing to their unique pleiotropic functions and therapeutic properties. Currently, clinical trial efforts using MSCs and MSC-based products are underway but clinical data collected by the early phase trials are insufficient to offer better support for the MSC-based anti-fibrotic therapies. Given that MSCs are involved in the coagulation through releasing tissue factor, MSCs can retain procoagulant activity to be associated with fibrogenic disease development. Therefore, MSCs’ functional benefits in translational applications need to be carefully balanced with their potential risks.
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Affiliation(s)
- Chenghai Li
- Stem Cell Program of Clinical Research Center, People’s Hospital of Zhengzhou University and Henan Provincial People’s Hospital, Zhengzhou, China
- Henan Key Laboratory of Stem Cell Differentiation and Modification, Henan University, Zhengzhou, China
- *Correspondence: Chenghai Li, ; Bin Wang,
| | - Bin Wang
- Department of Neurosurgery, People’s Hospital of Zhengzhou University and Henan Provincial People’s Hospital, Zhengzhou, China
- *Correspondence: Chenghai Li, ; Bin Wang,
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Di Vincenzo M, Martino M, Lariccia V, Giancola G, Licini C, Di Benedetto G, Arnaldi G, Orciani M. Mesenchymal Stem Cells Exposed to Persistently High Glucocorticoid Levels Develop Insulin-Resistance and Altered Lipolysis: A Promising In Vitro Model to Study Cushing's Syndrome. Front Endocrinol (Lausanne) 2022; 13:816229. [PMID: 35282448 PMCID: PMC8907420 DOI: 10.3389/fendo.2022.816229] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Accepted: 01/20/2022] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND In Cushing's syndrome (CS), chronic glucocorticoid excess (GC) and disrupted circadian rhythm lead to insulin resistance (IR), diabetes mellitus, dyslipidaemia and cardiovascular comorbidities. As undifferentiated, self-renewing progenitors of adipocytes, mesenchymal stem cells (MSCs) may display the detrimental effects of excess GC, thus revealing a promising model to study the molecular mechanisms underlying the metabolic complications of CS. METHODS MSCs isolated from the abdominal skin of healthy subjects were treated thrice daily with GCs according to two different regimens: lower, circadian-decreasing (Lower, Decreasing Exposure, LDE) versus persistently higher doses (Higher, Constant Exposure, HCE), aimed at mimicking either the physiological condition or CS, respectively. Subsequently, MSCs were stimulated with insulin and glucose thrice daily, resembling food uptake and both glucose uptake/GLUT-4 translocation and the expression of LIPE, ATGL, IL-6 and TNF-α genes were analyzed at predefined timepoints over three days. RESULTS LDE to GCs did not impair glucose uptake by MSCs, whereas HCE significantly decreased glucose uptake by MSCs only when prolonged. Persistent signs of IR occurred after 30 hours of HCE to GCs. Compared to LDE, MSCs experiencing HCE to GCs showed a downregulation of lipolysis-related genes in the acute period, followed by overexpression once IR was established. CONCLUSIONS Preserving circadian GC rhythmicity is crucial to prevent the occurrence of metabolic alterations. Similar to mature adipocytes, MSCs suffer from IR and impaired lipolysis due to chronic GC excess: MSCs could represent a reliable model to track the mechanisms involved in GC-induced IR throughout cellular differentiation.
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Affiliation(s)
- Mariangela Di Vincenzo
- Histology, Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, Ancona, Italy
| | - Marianna Martino
- Division of Endocrinology and Metabolic Diseases, Department of Clinical and Molecular Sciences, Umberto I Hospital, Università Politecnica delle Marche, Ancona, Italy
| | - Vincenzo Lariccia
- Pharmacology, Department of Biomedical Sciences and Public Health, Università Politecnica delle Marche, Ancona, Italy
| | - Giulia Giancola
- Division of Endocrinology and Metabolic Diseases, Department of Clinical and Molecular Sciences, Umberto I Hospital, Università Politecnica delle Marche, Ancona, Italy
| | - Caterina Licini
- Histology, Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, Ancona, Italy
| | - Giovanni Di Benedetto
- Clinic of Plastic and Reconstructive Surgery, Department of Experimental and Clinical Medicine, Università Politecnica delle Marche, Ancona, Italy
| | - Giorgio Arnaldi
- Division of Endocrinology and Metabolic Diseases, Department of Clinical and Molecular Sciences, Umberto I Hospital, Università Politecnica delle Marche, Ancona, Italy
- *Correspondence: Giorgio Arnaldi,
| | - Monia Orciani
- Histology, Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, Ancona, Italy
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Picerno A, Stasi A, Franzin R, Curci C, di Bari I, Gesualdo L, Sallustio F. Why stem/progenitor cells lose their regenerative potential. World J Stem Cells 2021; 13:1714-1732. [PMID: 34909119 PMCID: PMC8641024 DOI: 10.4252/wjsc.v13.i11.1714] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Revised: 05/26/2021] [Accepted: 10/31/2021] [Indexed: 02/06/2023] Open
Abstract
Nowadays, it is clear that adult stem cells, also called as tissue stem cells, play a central role to repair and maintain the tissue in which they reside by their self-renewal ability and capacity of differentiating into distinct and specialized cells. As stem cells age, their renewal ability declines and their capacity to maintain organ homeostasis and regeneration is impaired. From a molecular perspective, these changes in stem cells properties can be due to several types of cell intrinsic injury and DNA aberrant alteration (i.e epigenomic profile) as well as changes in the tissue microenviroment, both into the niche and by systemic circulating factors. Strikingly, it has been suggested that aging-induced deterioration of stem cell functions may play a key role in the pathophysiology of the various aging-associated disorders. Therefore, understanding how resident stem cell age and affects near and distant tissues is fundamental. Here, we examine the current knowledge about aging mechanisms in several kinds of adult stem cells under physiological and pathological conditions and the principal aging-related changes in number, function and phenotype that determine the loss of tissue renewal properties. Furthermore, we examine the possible cell rejuvenation strategies. Stem cell rejuvenation may reverse the aging phenotype and the discovery of effective methods for inducing and differentiating pluripotent stem cells for cell replacement therapies could open up new possibilities for treating age-related diseases.
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Affiliation(s)
- Angela Picerno
- Department of Emergency and Organ Transplantation, University of Bari “Aldo Moro”, Bari 70124, Italy
| | - Alessandra Stasi
- Department of Emergency and Organ Transplantation, University of Bari “Aldo Moro”, Bari 70124, Italy
| | - Rossana Franzin
- Department of Emergency and Organ Transplantation, University of Bari “Aldo Moro”, Bari 70124, Italy
| | - Claudia Curci
- Department of Emergency and Organ Transplantation, University of Bari “Aldo Moro”, Bari 70124, Italy
| | - Ighli di Bari
- Department of Emergency and Organ Transplantation, University of Bari “Aldo Moro”, Bari 70124, Italy
| | - Loreto Gesualdo
- Department of Emergency and Organ Transplantation, University of Bari “Aldo Moro”, Bari 70124, Italy
| | - Fabio Sallustio
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, Bari 70124, Italy
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