Download Free Mechanotransduction Modulates The Effect Of Mechanical Forces Fluid Shear Stress And Cyclic Strain On Embryonic Stem Cell Differentiation Toward Vascular Endothelial Cells Book in PDF and EPUB Free Download. You can read online Mechanotransduction Modulates The Effect Of Mechanical Forces Fluid Shear Stress And Cyclic Strain On Embryonic Stem Cell Differentiation Toward Vascular Endothelial Cells and write the review.

Vascularization of tissue-engineered substitutes is imperative for successful implantation into sites of injury. Strategies to promote vascularization within tissue-engineered constructs have focused on incorporating endothelial or endothelial progenitor cells within the construct. However, since endothelial and endothelial progenitor cells are adult cell types and limited in number, acquiring quantities needed for regenerative medicine applications is not feasible. Pluriopotent stem cells have been explored as a cell source for tissue-engineered substitutes because of their inherent ability to differentiate into all somatic cell types, including endothelial cells (ECs). Current EC differentiation strategies require laborious and extensive culture periods, utilize large quantities of expensive growth factors and extracellular matrix, and generally yield heterogenous populations for which only a small percentage of the differentiated cells are ECs. In order to recapitulate in vivo embryonic stem cell (ESC) differentiation, 3D stem cell aggregates or embryoid bodies (EBs) have been employed in vitro. In the developing embryo, fluid shear stress, VEGF, and oxygen are instructive cues for endothelial differentiation and vasculogenesis. Thus, the objective of this work was to study the effects of fluid shear stress pre-conditioning of ESCs on EB endothelial differentiation and vasculogensis. The overall hypothesis is that exposing ESCs to fluid shear stress prior to EB differentiation will promote EB endothelial differentiation and vasculogenesis. Pre-conditioning ESCs with fluid shear stress modulated EB differentiation as well as endothelial cell-like cellular organization and EB morphogenesis. To further promote endothelial differentiation, ESCs pre-conditioned with shear were treated with VEGF. Exposing EBs formed from ESCs pre-conditioned with shear to low oxygen resulted in increased production of VEGF and formation of endothelial networks. The results of this work demonstrate the role that physical forces play in modulating stem cell fate and morphogenesis.
Mechanotransduction: Cell Signaling to Cell Response covers the cell machinery responsible for the process of mechanotransduction and the manner in which cells respond to an external mechanical stimulus. The effect of mechanical stimulus on individual cells and entire tissues is discussed, with an emphasis on the practical results of this physiological process. Mechanotransduction of stem cells and cancerous cells are also covered, along with future directions in this yet nascent field. This book gives insights on basic processes that occur (or may occur) in the human body as a result of the application of mechanical stimulus. It is ideal for both biomedical engineers and biologists, and is an ideal resource for teaching. It provides a current state of conceptual and practical aspects of the field and will enable students and professionals to venture further into this incipient area which is of fundamental importance to biomedical engineering and biology fields. Covers fundamental concepts of signaling in cells as a result of mechanical stimulus Includes the physiological results of mechanical stimulus on the human body Explores the advantages of mechanical loads on the human body
Mesenchymal stem cells (MSCs) may benefit vascular cell-based therapies as smooth muscle or endothelial cell substitutes or through paracrine actions to repair, replace, or regenerate vascular tissue. Previous studies have demonstrated that MSCs can adopt traits of smooth muscle cells (SMCs) or endothelial cells (ECs), as well as secrete specific factors that tune signaling and material properties in the local environment. Few studies have investigated the cell signaling response of MSCs to mechanical forces present in the vasculature: specifically, shear stress due to blood flow and cyclic strain due to pulsatile blood flow. Thus, the central objective of this dissertation was to determine the signaling responses of MSCs to vascular-relevant applied physical forces, in comparison with that of differentiated vascular cells.
This book collects articles on the biology of hematopoietic stem cells during embryonic development, reporting on fly, fish, avian and mammalian models. The text invites a comparative overview of hematopoietic stem cell generation in the different classes, emphasizing conserved trends in development. The book reviews current knowledge on human hematopoietic development and discusses recent breakthroughs of relevance to both researchers and clinicians.
The structural, biochemical and clinical events related to menstruation, implantation, parturition, endometriosis, abnormal uterine bleeding and endometrial cancer are discussed in this comprehensive volume on the biological functions of the endometrium. New topics, such as the biochemical and molecular mechanisms regulating maternal embryonic interaction, are explored, and gynecologic endoscopy and therapeutic tools are discussed. The proceedings of the first conference is also available from the Academy, as volume 622 of The Annals of The New York Academy of Science.
Emphasizes the research activities of Germany’s Nauheim Institute of the Max Planck Society and its group of investigators both past and present, in the field of collateral artery growth. Incorporates a multidisciplinary in vivo approach to the study of arteriogenesis that includes molecular approaches with classical physiology and immunohistochemistry. Full color throughout and well illustrated.
The objective of this doctoral thesis was to investigate the effects of laminar fluid shear stress on the function three types of adult stem cells: mesenchymal stem cells, neural crest stem cells and multipotent vascular stem cells. These three types of stem cells represent potential cell sources for vascular tissue engineering. Before these stem cells can be used to create tissue engineered vascular grafts, a thorough understanding of the effects of hemodynamic forces on their function is necessary. Much like cyclical stretch and normal pressure, fluid shear stress plays a major role in the microenvironment of the blood vessel wall but the effects of this mechanical force on the function of these adult stem cells is not well understood. First, we began by investigating the effects of laminar fluid shear stress on TGF-beta1/SMAD2 signaling in human mesenchymal stem cells. Human mesenchymal cells (hMSCs) are multipotent fibroblast-like cells, which are found primarily in the bone marrow. MSCs are a potential cell source for tissue engineering because of their ease of isolation and expansion, their multipotency and their low immunogenicity. We found that exposing hMSCs to fluid flow promotes transforming growth factor 1 (TGF-beta1) signaling in a receptor-dependent manner. The mechanism explaining this phenomenon, however, was unclear. Based on our results, we rejected several hypotheses to explain the observed phenomenon: shear force transmission through the glycocalyx; changes in membrane fluidity; and changes in the internalization of TGF-beta; receptors. We were able to show that the increase in TGF-beta1/Smad2 signaling when hMSC are exposed to fluid flow was not caused by shear stress but instead, by an increase in the flow rate. We were also able to show that shear stress inhibits TGF-beta1/Smad2 signaling. Second, we examined the effects of laminar fluid shear stress on the function of human neural crest stem cells. Neural crest stem cells (NCSCs) are multipotent cells that give rise to various tissues during the embryonic development of vertebrates. NCSCs were derived from induced pluripotent stem cells and, then, exposed to a laminar fluid shear stress of 10 dynes/cm2 for various time periods. We found that laminar fluid shear stress increased NCSC proliferation. We also showed that fluid shear stress increased the activation of ERK1/2 in a time dependent manner. In addition, we observed that exposure to laminar fluid shear stress did not affect myogenic, neurogenic or osteogenic differentiation in NCSCs. We found, however, that exposure to fluid shear stress prevented adipogenic differentiation. Third, we explored the effects of laminar fluid shear stress on the function of multipotent vascular stem cells. Multipotent vascular stem cells (MVSCs) are adult stem cells that have recently been discovered in the medial layer of blood vessels. MVSCs have been shown to give rise to a variety of cell types including: schwann cells, peripheral neurons, smooth muscle cells, adipocytes, chondrocytes and osteocytes. MVSCs were isolated from rat carotid arteries. These cells were then expanded without differentiation and exposed to a laminar fluid shear stress of 6 dynes/cm2. We found that laminar fluid shear stress increased rat MVSC proliferation. We also showed that fluid shear stress increased the activation of ERK1/2 in a time dependent manner in MVSCs. Laminar fluid shear stress also caused a decrease in the gene expression of smooth muscle cell markers and an increase in the expression of osteoblastic differentiation genes. In addition, we observed that exposure to fluid shear stress did not affect myogenic, osteogenic and neurogenic cell differentiation in MVSCs. The results of the aforementioned studies provide new clues in efforts to elucidate the mechanobiology of adult stem cells but further investigation into the effects of mechanical stimulation on the function of human MSCs, NCSCs and MVSCs will be necessary to provide a rational basis for the use of these cells in tissue engineering applications.
A state-of-the-art primer on the role of pharmacological sciences in regenerative medicine, for advanced students, postdoctoral fellows, and researchers.