scholarly journals Insight into Mechanobiology: How Stem Cells Feel Mechanical Forces and Orchestrate Biological Functions

2019 ◽  
Vol 20 (21) ◽  
pp. 5337 ◽  
Author(s):  
Chiara Argentati ◽  
Francesco Morena ◽  
Ilaria Tortorella ◽  
Martina Bazzucchi ◽  
Serena Porcellati ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Biology ◽  
Current Knowledge ◽  
Ex Vivo ◽  
Active Role ◽  
Biological Functions ◽  
Cell Functions ◽  
Dynamic Relationship ◽  
Physical Stimuli

The cross-talk between stem cells and their microenvironment has been shown to have a direct impact on stem cells’ decisions about proliferation, growth, migration, and differentiation. It is well known that stem cells, tissues, organs, and whole organisms change their internal architecture and composition in response to external physical stimuli, thanks to cells’ ability to sense mechanical signals and elicit selected biological functions. Likewise, stem cells play an active role in governing the composition and the architecture of their microenvironment. Is now being documented that, thanks to this dynamic relationship, stemness identity and stem cell functions are maintained. In this work, we review the current knowledge in mechanobiology on stem cells. We start with the description of theoretical basis of mechanobiology, continue with the effects of mechanical cues on stem cells, development, pathology, and regenerative medicine, and emphasize the contribution in the field of the development of ex-vivo mechanobiology modelling and computational tools, which allow for evaluating the role of forces on stem cell biology.

scholarly journals Potential Use of Stem Cells for Kidney Regeneration

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Takashi Yokoo ◽  
Kei Matsumoto ◽  
Shinya Yokote
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Stem Cell Research ◽  
Cell Biology ◽  
Current Knowledge ◽  
Kidney Regeneration ◽  
Major Step ◽  
Kidney Dialysis ◽  
Organ Regeneration ◽  
Renal Stem Cell

Significant advances have been made in stem cell research over the past decade. A number of nonhematopoietic sources of stem cells (or progenitor cells) have been identified, including endothelial stem cells and neural stem cells. These discoveries have been a major step toward the use of stem cells for potential clinical applications of organ regeneration. Accordingly, kidney regeneration is currently gaining considerable attention to replace kidney dialysis as the ultimate therapeutic strategy for renal failure. However, due to anatomic complications, the kidney is believed to be the hardest organ to regenerate; it is virtually impossible to imagine such a complicated organ being completely rebuilt from pluripotent stem cells by gene or chemical manipulation. Nevertheless, several groups are taking on this big challenge. In this manuscript, current advances in renal stem cell research are reviewed and their usefulness for kidney regeneration discussed. We also reviewed the current knowledge of the emerging field of renal stem cell biology.

Mesenchymal stem cells in rheumatology: a regenerative approach to joint repair

2007 ◽  
Vol 113 (8) ◽  
pp. 339-348 ◽  
Author(s):  
Cosimo De Bari ◽  
Francesco Dell'Accio
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Cell Biology ◽  
Current Knowledge ◽  
Treatment Options ◽  
Joint Destruction ◽  
Tissue Remodelling ◽  
Regenerative Approach

The advent of biologics in rheumatology has considerably changed the evolution and prognosis of chronic inflammatory arthritis. The success of these new treatments has contributed to steering more attention to research focussed on repair and remodelling of joint tissues. Indeed, when the tissue damage is established, treatment options are very limited and the risk of progression towards joint destruction and failure remains high. Increasing evidence indicates that mesenchymal stem cells persist postnatally within joint tissues. It is postulated that they would function to safeguard joint homoeostasis and guarantee tissue remodelling and repair throughout life. Alterations in mesenchymal stem cell biology in arthritis have indeed been reported but a causal relationship has not been demonstrated, mainly because our current knowledge of mesenchymal stem cell niches and functions within the joint in health and disease is very limited. Nonetheless, mesenchymal stem cell technologies have attracted the attention of the biomedical research community as very promising tools to achieve the repair of joint tissues such as articular cartilage, subchondral bone, menisci and tendons. This review will outline stem-cell-mediated strategies for the repair of joint tissues, spanning from the use of expanded mesenchymal stem cell populations to therapeutic targeting of endogenous stem cells, resident in their native tissues, and related reparative signals in traumatic, degenerative and inflammatory joint disorders.

Paving the road for lung stem cell biology: bronchioalveolar stem cells and other putative distal lung stem cells

2007 ◽  
Vol 293 (5) ◽  
pp. L1092-L1098 ◽  
Author(s):  
Carla F. Kim
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Biology ◽  
The United States ◽  
Chronic Obstructive ◽  
Stem Cell Biology ◽  
Adult Lung ◽  
Cell Functions ◽  
Isolation And Characterization

New discoveries in stem cell biology are making the biology of solid tissues increasingly complex. Important seminal studies demonstrating the presence of damage-resistant cell populations together with new isolation and characterization techniques suggest that stem cells exist in the adult lung. More detailed in vivo molecular and cellular characterization of bronchioalveolar stem cells (BASCs), other putative lung stem and progenitor cells, and differentiated cells is needed to determine the lineage relationships in adult lung. Lung diseases such as cystic fibrosis or chronic obstructive pulmonary disease, as well as the most common form of lung cancer in the United States, all involve apparent bronchiolar and alveolar cell defects. It is likely that the delicate balance of stem, progenitor, and differentiated cell functions in the lung is critically affected in patients with these devastating diseases. Thus the discovery of BASCs and other putative lung stem cells will lay the foundation for new inroads to understanding lung biology related to lung disease.

scholarly journals NADPH Oxidases: Redox Regulators of Stem Cell Fate and Function

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 973
Author(s):  
Tullia Maraldi ◽  
Cristina Angeloni ◽  
Cecilia Prata ◽  
Silvana Hrelia
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Fate ◽  
Cell Biology ◽  
Immune Modulation ◽  
Ex Vivo ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Human Stem Cells ◽  
Stem Cell Fate

One of the major sources of reactive oxygen species (ROS) generated within stem cells is the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase family of enzymes (NOXs), which are critical determinants of the redox state beside antioxidant defense mechanisms. This balance is involved in another one that regulates stem cell fate: indeed, self-renewal, proliferation, and differentiation are decisive steps for stem cells during embryo development, adult tissue renovation, and cell therapy application. Ex vivo culture-expanded stem cells are being investigated for tissue repair and immune modulation, but events such as aging, senescence, and oxidative stress reduce their ex vivo proliferation, which is crucial for their clinical applications. Here, we review the role of NOX-derived ROS in stem cell biology and functions, focusing on positive and negative effects triggered by the activity of different NOX isoforms. We report recent findings on downstream molecular targets of NOX-ROS signaling that can modulate stem cell homeostasis and lineage commitment and discuss the implications in ex vivo expansion and in vivo engraftment, function, and longevity. This review highlights the role of NOX as a pivotal regulator of several stem cell populations, and we conclude that these aspects have important implications in the clinical utility of stem cells, but further studies on the effects of pharmacological modulation of NOX in human stem cells are imperative.

scholarly journals Primordial Germ Cells: Current Knowledge and Perspectives

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Aleksandar Nikolic ◽  
Vladislav Volarevic ◽  
Lyle Armstrong ◽  
Majlinda Lako ◽  
Miodrag Stojkovic
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Pluripotent Stem Cells ◽  
Cell Biology ◽  
Current Knowledge ◽  
Primordial Germ Cells ◽  
Primordial Germ Cell ◽  
Medical Application ◽  
Therapeutic Possibility

Infertility is a condition that occurs very frequently and understanding what defines normal fertility is crucial to helping patients. Causes of infertility are numerous and the treatment often does not lead to desired pregnancy especially when there is a lack of functional gametes. In humans, the primordial germ cell (PGC) is the primary undifferentiated stem cell type that will differentiate towards gametes: spermatozoa or oocytes. With the development of stem cell biology and differentiation protocols, PGC can be obtained from pluripotent stem cells providing a new therapeutic possibility to treat infertile couples. Recent studies demonstrated that viable mouse pups could be obtained fromin vitrodifferentiated stem cells suggesting that translation of these results to human is closer. Therefore, the aim of this review is to summarize current knowledge about PGC indicating the perspective of their use in both research and medical application for the treatment of infertility.

Metabolic Regulation and Related Molecular Mechanisms in Various Stem Cell Functions

2020 ◽  
Vol 15 (6) ◽  
pp. 531-546 ◽  
Author(s):  
Hwa-Yong Lee ◽  
In-Sun Hong
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Oxidative Phosphorylation ◽  
Metabolic Pathways ◽  
Critical Role ◽  
The Self ◽  
Specific Cell ◽  
Differentiation Potential ◽  
Self Renewal ◽  
Cell Functions

Recent studies on the mechanisms that link metabolic changes with stem cell fate have deepened our understanding of how specific metabolic pathways can regulate various stem cell functions during the development of an organism. Although it was originally thought to be merely a consequence of the specific cell state, metabolism is currently known to play a critical role in regulating the self-renewal capacity, differentiation potential, and quiescence of stem cells. Many studies in recent years have revealed that metabolic pathways regulate various stem cell behaviors (e.g., selfrenewal, migration, and differentiation) by modulating energy production through glycolysis or oxidative phosphorylation and by regulating the generation of metabolites, which can modulate multiple signaling pathways. Therefore, a more comprehensive understanding of stem cell metabolism could allow us to establish optimal culture conditions and differentiation methods that would increase stem cell expansion and function for cell-based therapies. However, little is known about how metabolic pathways regulate various stem cell functions. In this context, we review the current advances in metabolic research that have revealed functional roles for mitochondrial oxidative phosphorylation, anaerobic glycolysis, and oxidative stress during the self-renewal, differentiation and aging of various adult stem cell types. These approaches could provide novel strategies for the development of metabolic or pharmacological therapies to promote the regenerative potential of stem cells and subsequently promote their therapeutic utility.

scholarly journals GSK3β, a Master Kinase in the Regulation of Adult Stem Cell Behavior

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 225
Author(s):  
Claire Racaud-Sultan ◽  
Nathalie Vergnolle
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Adult Stem Cells ◽  
Glycogen Synthase ◽  
Inflammatory Diseases ◽  
Adult Stem Cell ◽  
Leukemic Cells ◽  
Cell Phenotype ◽  
Epithelial Regeneration ◽  
Cell Functions

In adult stem cells, Glycogen Synthase Kinase 3β (GSK3β) is at the crossroad of signaling pathways controlling survival, proliferation, adhesion and differentiation. The microenvironment plays a key role in the regulation of these cell functions and we have demonstrated that the GSK3β activity is strongly dependent on the engagement of integrins and protease-activated receptors (PARs). Downstream of the integrin α5β1 or PAR2 activation, a molecular complex is organized around the scaffolding proteins RACK1 and β-arrestin-2 respectively, containing the phosphatase PP2A responsible for GSK3β activation. As a consequence, a quiescent stem cell phenotype is established with high capacities to face apoptotic and metabolic stresses. A protective role of GSK3β has been found for hematopoietic and intestinal stem cells. Latters survived to de-adhesion through PAR2 activation, whereas formers were protected from cytotoxicity through α5β1 engagement. However, a prolonged activation of GSK3β promoted a defect in epithelial regeneration and a resistance to chemotherapy of leukemic cells, paving the way to chronic inflammatory diseases and to cancer resurgence, respectively. In both cases, a sexual dimorphism was measured in GSK3β-dependent cellular functions. GSK3β activity is a key marker for inflammatory and cancer diseases allowing adjusted therapy to sex, age and metabolic status of patients.

scholarly journals Conditionally immortalised leukaemia initiating cells co-expressing Hoxa9/Meis1 demonstrate microenvironmental adaptation properties ex vivo while maintaining myelomonocytic memory

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Maike Stahlhut ◽  
Teng Cheong Ha ◽  
Ekaterina Takmakova ◽  
Michael A. Morgan ◽  
Adrian Schwarzer ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Cell Lines ◽  
Cell Biology ◽  
Ex Vivo ◽  
Haematopoietic Stem Cell ◽  
Transcriptional Dysregulation ◽  
Conditional Gene Expression ◽  
Exponential Expansion ◽  
Drug Dependent

AbstractRegulation of haematopoietic stem cell fate through conditional gene expression could improve understanding of healthy haematopoietic and leukaemia initiating cell (LIC) biology. We established conditionally immortalised myeloid progenitor cell lines co-expressing constitutive Hoxa9.EGFP and inducible Meis1.dTomato (H9M-ciMP) to study growth behaviour, immunophenotype and morphology under different cytokine/microenvironmental conditions ex vivo upon doxycycline (DOX) induction or removal. The vector design and drug-dependent selection approach identified new retroviral insertion (RVI) sites that potentially collaborate with Meis1/Hoxa9 and define H9M-ciMP fate. For most cell lines, myelomonocytic conditions supported reversible H9M-ciMP differentiation into neutrophils and macrophages with DOX-dependent modulation of Hoxa9/Meis1 and CD11b/Gr-1 expression. Here, up-regulation of Meis1/Hoxa9 promoted reconstitution of exponential expansion of immature H9M-ciMPs after DOX reapplication. Stem cell maintaining conditions supported selective H9M-ciMP exponential growth. H9M-ciMPs that had Ninj2 RVI and were cultured under myelomonocytic or stem cell maintaining conditions revealed the development of DOX-dependent acute myeloid leukaemia in a murine transplantation model. Transcriptional dysregulation of Ninj2 and distal genes surrounding RVI (Rad52, Kdm5a) was detected. All studied H9M-ciMPs demonstrated adaptation to T-lymphoid microenvironmental conditions while maintaining immature myelomonocytic features. Thus, the established system is relevant to leukaemia and stem cell biology.

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