Mending the Failing Heart with a Vascularized Cardiac Patch

Functional, stem-cell-containing cardiac grafts will require vascularized myocardial constructs to support their survival and integration into the host vasculature. Recently in Tissue Engineering, Part A, Lesman et al. (2009) reported the successful integration of vascular cells and hESC-derived cardiomyoctyes into stable grafts in rat recipients

The Role of Biomaterials as Angiogenic Modulators of Spinal Cord Injury: Mimetics of the Spinal Cord, Cell and Angiogenic Factor Delivery Agents

Spinal cord injury (SCI) represents an extremely debilitating condition for which no efficacious treatment is available. One of the main contributors to the inhospitable environment found in SCI is the vascular disruption that happens at the moment of injury that compromises the blood-spinal cord barrier (BSCB) and triggers a cascade of events that includes infiltration of inflammatory cells, ischemia and intraparenchymal hemorrhage. Due to the unsatisfactory nature of revascularization following SCI, restoring vascular perfusion and the BSCB seems an interesting way of modulating the lesion environment into a regenerative phenotype, with a potential increase in functional recovery. Certain biomaterials possess interesting features to enhance SCI therapies, and in fact have been applied as angiogenic promoters in other pathologies. The present mini-review intends to highlight the contribution that biomaterials could make in the development of novel therapeutic solutions able to restore proper vascularization and the BSCB.Prémios Santa Casa Neurociências – Prize Melo e Castro for Spinal Cord Injury Research; Portuguese Foundation for Science and Technology [Doctoral fellowship (PD/BDE/127835/2016) to LR; IF Development Grant IF/00111/2013 to AS; by National Funds through Grant TUBITAK/0007/2014]. This article has been developed under the scope of the projects NORTE-01-0145-FEDER-000013, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER). This work has been funded by FEDER funds, through the Competitiveness Factors Operational Programme (COMPETE), and by National funds, through the Foundation for Science and Technology (FCT), under the scope of the project POCI-01-0145-FEDER-007038info:eu-repo/semantics/publishedVersio

Synthesis and characterization of novel scaffold for bone tissue engineering based on Whartons´s jelly

A composite is a material made of more than one component, and the bond between the components is on a scale larger than the atomic scale. The objective of the present study was to synthesize and perform the structural characterization and biological evaluation of a new biocomposite (BCO) based on a novel combination of an organic and an inorganic phase, for bone tissue engineering applications. The organic phase consisted of Wharton´s Jelly (WJ), which was obtained from embryonic tissue following a protocol developed by our laboratory. The inorganic phase consisted of bioceramic particles (BC), produced by sintering hydroxyapatite (HA) with β- tricalcium phosphate (β-TCP), and bioactive glass particles (BG). Each phase of the BCO was fully characterized by SEM, EDS, XRD and FTIR. Biocompatibility was evaluated in vivo in the tibiae of Wistar rats (n=40). Histological evaluation was performed at 0, 1, 7, 14, 30 and 60 days. XRD showed the phases corresponding to HA and β-TCP, whereas diffractogram of BG showed it to have an amorphous structure. EDS showed mainly Si and Na, Ca, P in BG, and Ca and P in HA and β-TCP. FTIR identified bonds between the organic and inorganic phases. From a mechanical viewpoint, the composite showed high flexural strength of 40.3±0.8MPa. The synthesized BCO exhibited adequate biocompatibility as shown by formation of lamellar type bone linked by BG and BC particles. The biomaterial presented here showed excellent mechanical and biocompatibility properties for its potential clinical use.Fil: Martinez, Cristian. Universidad de Buenos Aires. Facultad de Ingenieria. Instituto de Ingeniería Biomédica; Argentina. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Anatomía Patológica; Argentina. Universidad Nacional de Cuyo. Facultad de Odontologia; ArgentinaFil: Fernández, Carlos. Universidad de Buenos Aires. Facultad de Ingenieria. Instituto de Ingeniería Biomédica; ArgentinaFil: Prado, Miguel Oscar. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ozols, Andres. Universidad de Buenos Aires. Facultad de Ingenieria. Instituto de Ingeniería Biomédica; ArgentinaFil: Olmedo, Daniel Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Anatomía Patológica; Argentin

Bone marrow stromal cells stimulate an angiogenic program that requires endothelial MT1‐MMP

Bone marrow‐derived stromal/stem cells (BMSCs) have recently been characterized as mediators of tissue regeneration after injury. In addition to preventing fibrosis at the wound site, BMSCs elicit an angiogenic response within the fibrin matrix. The mechanistic interactions between BMSCs and invading endothelial cells (ECs) during this process are not fully understood. Using a three‐dimensional, fibrin‐based angiogenesis model, we sought to investigate the proteolytic mechanisms by which BMSCs promote vessel morphogenesis. We find that BMSC‐mediated vessel formation depends on the proteolytic ability of membrane type 1‐matrix metalloproteinase (MT1‐MMP). Knockdown of the protease results in a small network of vessels with enlarged lumens. Contrastingly, vessel morphogenesis is unaffected by the knockdown of MMP‐2 and MMP‐9. Furthermore, we find that BMSC‐mediated vessel morphogenesis in vivo follows mechanisms similar to what we observe in vitro. Subcutaneous, cellular fibrin implants in C.B‐17/SCID mice form aberrant vasculature when MMPs are inhibited with a broad‐spectrum chemical inhibitor, and a very minimal amount of vessels when MT1‐MMP proteolytic activity is interrupted in ECs. Other studies have debated the necessity of MT1‐MMP in the context of vessel invasion in fibrin, but this study clearly demonstrates its requirement in BMSC‐mediated angiogenesis. J. Cell. Physiol. 227: 3546–3555, 2012. © 2012 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/92409/1/24056_ftp.pd

Microfluidic traction force microscopy to study mechanotransduction in angiogenesis.

The formation of new blood vessels from existing vasculature, angiogenesis, is driven by coordinated endothelial cell migration and matrix remodelling in response to local signals. Recently, a growing body of evidence has shown that mechanotransduction, along with chemotransduction, is a major regulator of angiogenesis. Mechanical signals, such as fluid shear stress and substrate mechanics, influence sprouting and network formation, but the mechanisms behind this relationship are still unclear. Here, we present cellular traction forces as possible effectors activated by mechanosensing to mediate matrix remodelling, and encourage the use of traction force microscopy to study mechanotransduction in angiogenesis. We also suggest that deciphering the response of endothelial cells to mechanical signals could reveal an optimal angiogenic mechanical environment, and provide insight into development, wound healing, the initiation and growth of tumours, and new strategies for tissue engineering. This article is protected by copyright. All rights reserved

Mechanotransduction and growth factor signalling to engineer cellular microenvironments

Engineering cellular microenvironments involves biochemical factors, the extracellular matrix (ECM) and the interaction with neighbouring cells. This progress report provides a critical overview of key studies that incorporate growth factor (GF) signalling and mechanotransduction into the design of advanced microenvironments. Materials systems have been developed for surface-bound presentation of GFs, either covalently tethered or sequestered through physico-chemical affinity to the matrix, as an alternative to soluble GFs. Furthermore, some materials contain both GF and integrin binding regions and thereby enable synergistic signalling between the two. Mechanotransduction refers to the ability of the cells to sense physical properties of the ECM and to transduce them into biochemical signals. Various aspects of the physics of the ECM, i.e. stiffness, geometry and ligand spacing, as well as time-dependent properties, such as matrix stiffening, degradability, viscoelasticity, surface mobility as well as spatial patterns and gradients of physical cues are discussed. To conclude, various examples illustrate the potential for cooperative signalling of growth factors and the physical properties of the microenvironment for potential applications in regenerative medicine, cancer research and drug testing

Insulin-Like Growth Factors Promote Vasculogenesis in Embryonic Stem Cells

The ability of embryonic stem cells to differentiate into endothelium and form functional blood vessels has been well established and can potentially be harnessed for therapeutic angiogenesis. However, after almost two decades of investigation in this field, limited knowledge exists for directing endothelial differentiation. A better understanding of the cellular mechanisms regulating vasculogenesis is required for the development of embryonic stem cell-based models and therapies. In this study, we elucidated the mechanistic role of insulin-like growth factors (IGF1 and 2) and IGF receptors (IGFR1 and 2) in endothelial differentiation using an embryonic stem cell embryoid body model. Both IGF1 or IGF2 predisposed embryonic stem to differentiate towards a mesodermal lineage, the endothelial precursor germ layer, as well as increased the generation of significantly more endothelial cells at later stages. Inhibition of IGFR1 signaling using neutralizing antibody or a pharmacological inhibitor, picropodophyllin, significantly reduced IGF-induced mesoderm and endothelial precursor cell formation. We confirmed that IGF-IGFR1 signaling stabilizes HIF1α and leads to up-regulation of VEGF during vasculogenesis in embryoid bodies. Understanding the mechanisms that are critical for vasculogenesis in various models will bring us one step closer to enabling cell based therapies for neovascularization

Endothelial progenitor cells and integrins: adhesive needs

In the last decade there have been multiple studies concerning the contribution of endothelial progenitor cells (EPCs) to new vessel formation in different physiological and pathological settings. The process by which EPCs contribute to new vessel formation in adults is termed postnatal vasculogenesis and occurs via four inter-related steps. They must respond to chemoattractant signals and mobilize from the bone marrow to the peripheral blood; home in on sites of new vessel formation; invade and migrate at the same sites; and differentiate into mature endothelial cells (ECs) and/or regulate pre-existing ECs via paracrine or juxtacrine signals. During these four steps, EPCs interact with different physiological compartments, namely bone marrow, peripheral blood, blood vessels and homing tissues. The success of each step depends on the ability of EPCs to interact, adapt and respond to multiple molecular cues. The present review summarizes the interactions between integrins expressed by EPCs and their ligands: extracellular matrix components and cell surface proteins present at sites of postnatal vasculogenesis. The data summarized here indicate that integrins represent a major molecular determinant of EPC function, with different integrin subunits regulating different steps of EPC biology. Specifically, integrin α4β1 is a key regulator of EPC retention and/or mobilization from the bone marrow, while integrins α5β1, α6β1, αvβ3 and αvβ5 are major determinants of EPC homing, invasion, differentiation and paracrine factor production. β2 integrins are the major regulators of EPC transendothelial migration. The relevance of integrins in EPC biology is also demonstrated by many studies that use extracellular matrix-based scaffolds as a clinical tool to improve the vasculogenic functions of EPCs. We propose that targeted and tissue-specific manipulation of EPC integrin-mediated interactions may be crucial to further improve the usage of this cell population as a relevant clinical agent

Analisis knowledge inertia dalam inovasi produk kopi pada preharvest dan post-harvest periods di koperasi Solok Radjo.

ix, 124 hlm.; 23 c