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 Tuning Adipogenic Differentiation in ADSCs by Metformin and Vitamin D: Involvement of miRNAs

2020 ◽  
Vol 21 (17) ◽  
pp. 6181
Author(s):  
Sara Cruciani ◽  
Giuseppe Garroni ◽  
Francesca Balzano ◽  
Renzo Pala ◽  
Emanuela Bellu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Vitamin D ◽  
Stem Cell ◽  
Cell Fate ◽  
Adipogenic Differentiation ◽  
Adipose Derived Stem Cells ◽  
Vitamin D Metabolism ◽  
Stem Cell Fate ◽  
Cellular Phenotypes

Fat tissue represents an important source of adipose-derived stem cells (ADSCs), which can differentiate towards several phenotypes under certain stimuli. Definite molecules as vitamin D are able to influence stem cell fate, acting on the expression of specific genes. In addition, miRNAs are important modulating factors in obesity and numerous diseases. We previously identified specific conditioned media able to commit stem cells towards defined cellular phenotypes. In the present paper, we aimed at evaluating the role of metformin on ADSCs differentiation. In particular, ADSCs were cultured in a specific adipogenic conditioned medium (MD), in the presence of metformin, alone or in combination with vitamin D. Our results showed that the combination of the two compounds is able to counteract the appearance of an adipogenic phenotype, indicating a feedforward regulation on vitamin D metabolism by metformin, acting on CYP27B1 and CYP3A4. We then evaluated the role of specific epigenetic modulating genes and miRNAs in controlling stem cell adipogenesis. The combination of the two molecules was able to influence stem cell fate, by modulating the adipogenic phenotype, suggesting their possible application in clinical practice in counteracting uncontrolled lipogenesis and obesity-related diseases.

scholarly journals Effects of Oxidative Stress on Mesenchymal Stem Cell Biology

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Ryan A. Denu ◽  
Peiman Hematti
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Cell Biology ◽  
Immune Modulation ◽  
Ex Vivo ◽  
Multipotent Stem Cells ◽  
Clinical Potential ◽  
Stromal Stem Cells

Mesenchymal stromal/stem cells (MSCs) are multipotent stem cells present in most fetal and adult tissues.Ex vivoculture-expanded MSCs are being investigated for tissue repair and immune modulation, but their full clinical potential is far from realization. Here we review the role of oxidative stress in MSC biology, as their longevity and functions are affected by oxidative stress. In general, increased reactive oxygen species (ROS) inhibit MSC proliferation, increase senescence, enhance adipogenic but reduce osteogenic differentiation, and inhibit MSC immunomodulation. Furthermore, aging, senescence, and oxidative stress reduce theirex vivoexpansion, which is critical for their clinical applications. Modulation of sirtuin expression and activity may represent a method to reduce oxidative stress in MSCs. These findings have important implications in the clinical utility of MSCs for degenerative and immunological based conditions. Further study of oxidative stress in MSCs is imperative in order to enhance MSCex vivoexpansion andin vivoengraftment, function, and longevity.

scholarly journals Advances in Extracellular Matrix-Mimetic Hydrogels to Guide Stem Cell Fate

2021 ◽  
pp. 1-18
Author(s):  
Ryan S. Stowers
Keyword(s):  
Stem Cells ◽  
Extracellular Matrix ◽  
Stem Cell ◽  
Cell Fate ◽  
Cell Biology ◽  
Stem Cell Differentiation ◽  
Stem Cell Biology ◽  
Stem Cell Fate ◽  
Material Systems

In the fields of regenerative medicine and tissue engineering, stem cells offer vast potential for treating or replacing diseased and damaged tissue. Much progress has been made in understanding stem cell biology, yielding protocols for directing stem cell differentiation toward the cell type of interest for a specific application. One particularly interesting and powerful signaling cue is the extracellular matrix (ECM) surrounding stem cells, a network of biopolymers that, along with cells, makes up what we define as a tissue. The composition, structure, biochemical features, and mechanical properties of the ECM are varied in different tissues and developmental stages, and serve to instruct stem cells toward a specific lineage. By understanding and recapitulating some of these ECM signaling cues through engineered ECM-mimicking hydrogels, stem cell fate can be directed in vitro. In this review, we will summarize recent advances in material systems to guide stem cell fate, highlighting innovative methods to capture ECM functionalities and how these material systems can be used to provide basic insight into stem cell biology or make progress toward therapeutic objectives.

scholarly journals The physical microenvironment of hematopoietic stem cells and its emerging roles in engineering applications

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Pan Zhang ◽  
Chen Zhang ◽  
Jing Li ◽  
Jiyang Han ◽  
Xiru Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Hematopoietic Stem Cells ◽  
Cell Fate ◽  
Hematopoietic Stem Cell ◽  
Ex Vivo ◽  
Hematopoietic Stem ◽  
Stem Cell Fate ◽  
Stem Cell Engineering

AbstractStem cells are considered the fundamental underpinnings of tissue biology. The stem cell microenvironment provides factors and elements that play significant roles in controlling the cell fate direction. The bone marrow is an important environment for functional hematopoietic stem cells in adults. Remarkable progress has been achieved in the area of hematopoietic stem cell fate modulation based on the recognition of biochemical factors provided by bone marrow niches. In this review, we focus on emerging evidence that hematopoietic stem cell fate is altered in response to a variety of microenvironmental physical cues, such as geometric properties, matrix stiffness, and mechanical forces. Based on knowledge of these biophysical cues, recent developments in harnessing hematopoietic stem cell niches ex vivo are also discussed. A comprehensive understanding of cell microenvironments helps provide mechanistic insights into pathophysiological mechanisms and underlies biomaterial-based hematopoietic stem cell engineering.

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.

scholarly journals The dynamic role of bone morphogenetic proteins in neural stem cell fate and maturation

2012 ◽  
Vol 72 (7) ◽  
pp. 1068-1084 ◽  
Author(s):  
Allison M. Bond ◽  
Oneil G. Bhalala ◽  
John A. Kessler
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Neural Stem Cell ◽  
Bone Morphogenetic Proteins ◽  
Stem Cell Fate

scholarly journals The Winding Road of Cardiac Regeneration—Stem Cell Omics in the Spotlight

Cells ◽  
2018 ◽  
Vol 7 (12) ◽  
pp. 255 ◽  
Author(s):  
Miruna Mihaela Micheu ◽  
Alina Ioana Scarlatescu ◽  
Alexandru Scafa-Udriste ◽  
Maria Dorobantu
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Fate ◽  
Cell Biology ◽  
Molecular Mechanisms ◽  
Unmet Need ◽  
Cardiac Regeneration ◽  
Cell Types ◽  
Great Promise ◽  
Omics Data

Despite significant progress in treating ischemic cardiac disease and succeeding heart failure, there is still an unmet need to develop effective therapeutic strategies given the persistent high-mortality rate. Advances in stem cell biology hold great promise for regenerative medicine, particularly for cardiac regeneration. Various cell types have been used both in preclinical and clinical studies to repair the injured heart, either directly or indirectly. Transplanted cells may act in an autocrine and/or paracrine manner to improve the myocyte survival and migration of remote and/or resident stem cells to the site of injury. Still, the molecular mechanisms regulating cardiac protection and repair are poorly understood. Stem cell fate is directed by multifaceted interactions between genetic, epigenetic, transcriptional, and post-transcriptional mechanisms. Decoding stem cells’ “panomic” data would provide a comprehensive picture of the underlying mechanisms, resulting in patient-tailored therapy. This review offers a critical analysis of omics data in relation to stem cell survival and differentiation. Additionally, the emerging role of stem cell-derived exosomes as “cell-free” therapy is debated. Last but not least, we discuss the challenges to retrieve and analyze the huge amount of publicly available omics data.

Asymmetric organelle inheritance predicts human blood stem cell fate

Blood ◽  
2021 ◽  
Author(s):  
Dirk Loeffler ◽  
Florin Schneiter ◽  
Weijia Wang ◽  
Arne Wehling ◽  
Tobias Kull ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Division ◽  
Cell Fate ◽  
Human Blood ◽  
Asymmetric Cell Division ◽  
Cell Fates ◽  
Hematopoietic Stem ◽  
Stem Cell Fate ◽  
Blood Stem Cells

Understanding human hematopoietic stem cell fate control is important for their improved therapeutic manipulation. Asymmetric cell division, the asymmetric inheritance of factors during division instructing future daughter cell fates, was recently described in mouse blood stem cells. In human blood stem cells, the possible existence of asymmetric cell division remained unclear due to technical challenges in its direct observation. Here, we use long-term quantitative single-cell imaging to show that lysosomes and active mitochondria are asymmetrically inherited in human blood stem cells and that their inheritance is a coordinated, non-random process. Furthermore, multiple additional organelles, including autophagosomes, mitophagosomes, autolysosomes and recycling endosomes show preferential asymmetric co-segregation with lysosomes. Importantly, asymmetric lysosomal inheritance predicts future asymmetric daughter cell cycle length, differentiation and stem cell marker expression, while asymmetric inheritance of active mitochondria correlates with daughter metabolic activity. Hence, human hematopoietic stem cell fates are regulated by asymmetric cell division, with both mechanistic evolutionary conservation and differences to the mouse system.

scholarly journals The role of extracellular matrix on liver stem cell fate: A dynamic relationship in health and disease

2019 ◽  
Vol 106 ◽  
pp. 49-56 ◽  
Author(s):  
Natalia Sánchez-Romero ◽  
Pilar Sainz-Arnal ◽  
Iris Pla-Palacín ◽  
Pablo Royo Dachary ◽  
Helen Almeida ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Stem Cell ◽  
Cell Fate ◽  
Stem Cell Fate ◽  
Dynamic Relationship ◽  
Health And Disease
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