scholarly journals The Role of Stiffness in Cell Reprogramming: A Potential Role for Biomaterials in Inducing Tissue Regeneration

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 1036 ◽  
Author(s):  
Michele d’Angelo ◽  
Elisabetta Benedetti ◽  
Maria Grazia Tupone ◽  
Mariano Catanesi ◽  
Vanessa Castelli ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cell Fate ◽  
Tissue Regeneration ◽  
Cell Biology ◽  
New Technologies ◽  
Biomechanical Properties ◽  
Cell Reprogramming ◽  
Cell Behavior ◽  
Dependent Manner ◽  
Mechanical Stimuli

The mechanotransduction is the process by which cells sense mechanical stimuli such as elasticity, viscosity, and nanotopography of extracellular matrix and translate them into biochemical signals. The mechanotransduction regulates several aspects of the cell behavior, including migration, proliferation, and differentiation in a time-dependent manner. Several reports have indicated that cell behavior and fate are not transmitted by a single signal, but rather by an intricate network of many signals operating on different length and timescales that determine cell fate. Since cell biology and biomaterial technology are fundamentals in cell-based regenerative therapies, comprehending the interaction between cells and biomaterials may allow the design of new biomaterials for clinical therapeutic applications in tissue regeneration. In this work, we present the most relevant mechanism by which the biomechanical properties of extracellular matrix (ECM) influence cell reprogramming, with particular attention on the new technologies and materials engineering, in which are taken into account not only the biochemical and biophysical signals patterns but also the factor time.

scholarly journals Hypoxia in Cell Reprogramming and the Epigenetic Regulations

2021 ◽  
Vol 9 ◽  
Author(s):  
Nariaki Nakamura ◽  
Xiaobing Shi ◽  
Radbod Darabi ◽  
Yong Li
Keyword(s):  
Cell Proliferation ◽  
Cell Fate ◽  
Tissue Regeneration ◽  
Cellular Reprogramming ◽  
Cell Reprogramming ◽  
Cell Renewal ◽  
Cellular Functions ◽  
Stem Cell Renewal ◽  
Epigenetic Regulations

Cellular reprogramming is a fundamental topic in the research of stem cells and molecular biology. It is widely investigated and its understanding is crucial for learning about different aspects of development such as cell proliferation, determination of cell fate and stem cell renewal. Other factors involved during development include hypoxia and epigenetics, which play major roles in the development of tissues and organs. This review will discuss the involvement of hypoxia and epigenetics in the regulation of cellular reprogramming and how interplay between each factor can contribute to different cellular functions as well as tissue regeneration.

Cell Reprogramming: A New Chemical Approach to Stem Cell Biology and Tissue Regeneration

2011 ◽  
Vol 12 (2) ◽  
pp. 146-150 ◽  
Author(s):  
L. Anastasia ◽  
M. Piccoli ◽  
A. Garatti ◽  
E. Conforti ◽  
R. Scaringi ◽  
...  
Keyword(s):  
Stem Cell ◽  
Tissue Regeneration ◽  
Cell Biology ◽  
Cell Reprogramming ◽  
Stem Cell Biology ◽  
Chemical Approach

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 A New Approach for Glyco-Functionalization of Collagen-Based Biomaterials

2019 ◽  
Vol 20 (7) ◽  
pp. 1747 ◽  
Author(s):  
Ines Figuereido ◽  
Alice Paiotta ◽  
Roberta Dal Magro ◽  
Francesca Tinelli ◽  
Roberta Corti ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Extracellular Matrix ◽  
Cell Fate ◽  
Cell Biology ◽  
Aqueous Media ◽  
New Approach ◽  
Cell Microenvironment ◽  
Fate Control ◽  
Ecm Proteins ◽  
Cell Fate Control

The cell microenvironment plays a pivotal role in mediating cell adhesion, survival, and proliferation in physiological and pathological states. The relevance of extracellular matrix (ECM) proteins in cell fate control is an important issue to take into consideration for both tissue engineering and cell biology studies. The glycosylation of ECM proteins remains, however, largely unexplored. In order to investigate the physio-pathological effects of differential ECM glycosylation, the design of affordable chemoselective methods for ECM components glycosylation is desirable. We will describe a new chemoselective glycosylation approach exploitable in aqueous media and on non-protected substrates, allowing rapid access to glyco-functionalized biomaterials.

scholarly journals Interplay Between Notch and YAP/TAZ Pathways in the Regulation of Cell Fate During Embryo Development

2021 ◽  
Vol 9 ◽  
Author(s):  
Carolyn Engel-Pizcueta ◽  
Cristina Pujades
Keyword(s):  
Cell Fate ◽  
Cell Biology ◽  
Notch Pathway ◽  
Cell Communication ◽  
Tissue Growth ◽  
General Mechanism ◽  
Dependent Manner ◽  
Cell Fate Decisions ◽  
Physical Cues ◽  
Progenitor Maintenance

Cells in growing tissues receive both biochemical and physical cues from their microenvironment. Growing evidence has shown that mechanical signals are fundamental regulators of cell behavior. However, how physical properties of the microenvironment are transduced into critical cell behaviors, such as proliferation, progenitor maintenance, or differentiation during development, is still poorly understood. The transcriptional co-activators YAP/TAZ shuttle between the cytoplasm and the nucleus in response to multiple inputs and have emerged as important regulators of tissue growth and regeneration. YAP/TAZ sense and transduce physical cues, such as those from the extracellular matrix or the actomyosin cytoskeleton, to regulate gene expression, thus allowing them to function as gatekeepers of progenitor behavior in several developmental contexts. The Notch pathway is a key signaling pathway that controls binary cell fate decisions through cell–cell communication in a context-dependent manner. Recent reports now suggest that the crosstalk between these two pathways is critical for maintaining the balance between progenitor maintenance and cell differentiation in different tissues. How this crosstalk integrates with morphogenesis and changes in tissue architecture during development is still an open question. Here, we discuss how progenitor cell proliferation, specification, and differentiation are coordinated with morphogenesis to construct a functional organ. We will pay special attention to the interplay between YAP/TAZ and Notch signaling pathways in determining cell fate decisions and discuss whether this represents a general mechanism of regulating cell fate during development. We will focus on research carried out in vertebrate embryos that demonstrate the important roles of mechanical cues in stem cell biology and discuss future challenges.

scholarly journals Vitamin C in Stem Cell Biology: Impact on Extracellular Matrix Homeostasis and Epigenetics

2017 ◽  
Vol 2017 ◽  
pp. 1-16 ◽  
Author(s):  
Cristina D'Aniello ◽  
Federica Cermola ◽  
Eduardo Jorge Patriarca ◽  
Gabriella Minchiotti
Keyword(s):  
Stem Cells ◽  
Extracellular Matrix ◽  
Stem Cell ◽  
Vitamin C ◽  
Cell Fate ◽  
Cell Biology ◽  
Embryonic Stem ◽  
Redox Status ◽  
Stem Cell Biology ◽  
Prolyl Hydroxylases

Transcription factors and signaling molecules are well-known regulators of stem cell identity and behavior; however, increasing evidence indicates that environmental cues contribute to this complex network of stimuli, acting as crucial determinants of stem cell fate.L-Ascorbic acid (vitamin C (VitC)) has gained growing interest for its multiple functions and mechanisms of action, contributing to the homeostasis of normal tissues and organs as well as to tissue regeneration. Here, we review the main functions of VitC and its effects on stem cells, focusing on its activity as cofactor of Fe+2/αKG dioxygenases, which regulate the epigenetic signatures, the redox status, and the extracellular matrix (ECM) composition, depending on the enzymes’ subcellular localization. Acting as cofactor of collagen prolyl hydroxylases in the endoplasmic reticulum, VitC regulates ECM/collagen homeostasis and plays a key role in the differentiation of mesenchymal stem cells towards osteoblasts, chondrocytes, and tendons. In the nucleus, VitC enhances the activity of DNA and histone demethylases, improving somatic cell reprogramming and pushing embryonic stem cell towards the naive pluripotent state. The broad spectrum of actions of VitC highlights its relevance for stem cell biology in both physiology and disease.

scholarly journals Cell reprogramming modelled as transitions in a hierarchy of cell cycles

2016 ◽  
Author(s):  
R. Hannam ◽  
A. Annibale ◽  
R. Kühn
Keyword(s):  
Cell Fate ◽  
Cell Biology ◽  
A Priori ◽  
Cell Types ◽  
Cell Reprogramming ◽  
Cell Cycles ◽  
Cell Fate Decisions ◽  
Differentiated Cells ◽  
Cellular Environment ◽  
Experimental Findings

We construct a model of cell reprogramming (the conversion of fully differentiated cells to a state of pluripotency, known as induced pluripotent stem cells, or iPSCs) which builds on key elements of cell biology viz. cell cycles and cell lineages. Although reprogramming has been demonstrated experimentally, much of the underlying processes governing cell fate decisions remain unknown. This work aims to bridge this gap by modelling cell types as a set of hierarchically related dynamical attractors representing cell cycles. Stages of the cell cycle are characterised by the configuration of gene expression levels, and reprogramming corresponds to triggering transitions between such configurations. Two mechanisms were found for reprogramming in a two level hierarchy: cycle specific perturbations and a noise induced switching. The former corresponds to a directed perturbation that induces a transition into a cycle-state of a different cell type in the potency hierarchy (mainly a stem cell) whilst the latter is a priori undirected and could be induced, e.g., by a (stochastic) change in the cellular environment. These reprogramming protocols were found to be effective in large regimes of the parameter space and make specific predictions concerning reprogramming dynamics which are broadly in line with experimental findings.

scholarly journals Intrinsic Mechanical Cues and Their Impact on Stem Cells and Embryogenesis

2021 ◽  
Vol 9 ◽  
Author(s):  
Jonna Petzold ◽  
Eileen Gentleman
Keyword(s):  
Stem Cells ◽  
Extracellular Matrix ◽  
Cell Surface ◽  
Cell Fate ◽  
Cell Biology ◽  
Soft Tissues ◽  
Embryonic Stem ◽  
Focal Adhesions ◽  
Cell Fate Decisions ◽  
Applied Forces

Although understanding how soluble cues direct cellular processes revolutionised the study of cell biology in the second half of the 20th century, over the last two decades, new insights into how mechanical cues similarly impact cell fate decisions has gained momentum. During development, extrinsic cues such as fluid flow, shear stress and compressive forces are essential for normal embryogenesis to proceed. Indeed, both adult and embryonic stem cells can respond to applied forces, but they can also detect intrinsic mechanical cues from their surrounding environment, such as the stiffness of the extracellular matrix, which impacts differentiation and morphogenesis. Cells can detect changes in their mechanical environment using cell surface receptors such as integrins and focal adhesions. Moreover, dynamic rearrangements of the cytoskeleton have been identified as a key means by which forces are transmitted from the extracellular matrix to the cell and vice versa. Although we have some understanding of the downstream mechanisms whereby mechanical cues are translated into changes in cell behaviour, many of the signalling pathways remain to be defined. This review discusses the importance of intrinsic mechanical cues on adult cell fate decisions, the emerging roles of cell surface mechano-sensors and the cytoskeleton in enabling cells to sense its microenvironment, and the role of intracellular signalling in translating mechanical cues into transcriptional outputs. In addition, the contribution of mechanical cues to fundamental processes during embryogenesis such as apical constriction and convergent extension is discussed. The continued development of tools to measure the biomechanical properties of soft tissues in vivo is likely to uncover currently underestimated contributions of these cues to adult stem cell fate decisions and embryogenesis, and may inform on regenerative strategies for tissue repair.

scholarly journals Stem Cell Mechanobiology and the Role of Biomaterials in Governing Mechanotransduction and Matrix Production for Tissue Regeneration

2020 ◽  
Vol 8 ◽  
Author(s):  
S. M. Naqvi ◽  
L. M. McNamara
Keyword(s):  
Stem Cell ◽  
Tissue Regeneration ◽  
Cell Biology ◽  
Cell Behavior ◽  
Stem Cell Biology ◽  
Design Strategies ◽  
Stem Cell Migration ◽  
Biological Responses ◽  
Proliferation And Differentiation ◽  
Biomechanical Stimuli

Mechanobiology has underpinned many scientific advances in understanding how biophysical and biomechanical cues regulate cell behavior by identifying mechanosensitive proteins and specific signaling pathways within the cell that govern the production of proteins necessary for cell-based tissue regeneration. It is now evident that biophysical and biomechanical stimuli are as crucial for regulating stem cell behavior as biochemical stimuli. Despite this, the influence of the biophysical and biomechanical environment presented by biomaterials is less widely accounted for in stem cell-based tissue regeneration studies. This Review focuses on key studies in the field of stem cell mechanobiology, which have uncovered how matrix properties of biomaterial substrates and 3D scaffolds regulate stem cell migration, self-renewal, proliferation and differentiation, and activation of specific biological responses. First, we provide a primer of stem cell biology and mechanobiology in isolation. This is followed by a critical review of key experimental and computational studies, which have unveiled critical information regarding the importance of the biophysical and biomechanical cues for stem cell biology. This review aims to provide an informed understanding of the intrinsic role that physical and mechanical stimulation play in regulating stem cell behavior so that researchers may design strategies that recapitulate the critical cues and develop effective regenerative medicine approaches.

scholarly journals Extracellular matrix derived from Wharton’s Jelly-derived mesenchymal stem cells promotes angiogenesis via integrin αVβ3/c-Myc/P300/VEGF

2021 ◽  
Author(s):  
Beilei Ma ◽  
Tengkai Wang ◽  
Juan Li ◽  
Qian Wang
Keyword(s):  
Stem Cells ◽  
Extracellular Matrix ◽  
Mesenchymal Stem Cells ◽  
Tissue Regeneration ◽  
Umbilical Vein ◽  
Integrin Αvβ3 ◽  
Wharton’S Jelly ◽  
Dependent Manner ◽  
Wharton's Jelly

Abstract Background Angiogenesis is required in many physiological conditions, including bone regeneration, wound healing, and tissue regeneration. Cell-derived extracellular matrix (CD-ECM) could guide intricate cellular and tissue processes such as homeostasis, healing and regeneration. Methods The purpose of this study is to explore the effect and mechanism of ECM derived from decellularized Wharton's Jelly-derived mesenchymal stem cells (WJ-MSCs) on endothelial cell viability and angiogenesis. Results In this study, we found for the first time that WJ-MSCs ECM could improve the angiogenesis ability of human umbilical vein endothelial cells (HUVECs) with a time-dependent manner in vitro. Mechanically, WJ-MSCs ECM activated the focal adhesion kinase (FAK)/P38 signaling pathway via integrin αVβ3, which further promoted the expression of the cellular (c)-Myc. Further, c-Myc increased histone acetylation levels of the vascular endothelial growth factor (VEGF) promoter by recruiting P300, which ultimately promoting VEGF expression. Conclusions Extracellular matrix derived from Wharton’s Jelly-derived mesenchymal stem cells promotes angiogenesis via integrin αVβ3/c-Myc/P300/VEGF. This study is expected to provide a new approach to promote angiogenesis in bone and tissue regeneration.

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