Masanori Aikawa, an associate professor of medicine at Harvard Medical School, describes the new technology as «a monumental contribution» that should help researchers develop new treatments and learn more about diseases
of endothelial tissue such as atherosclerosis and diabetic retinopathy, which can cause blindness.
The dissection
of the endothelial tissues is diagrammed in Figure 1.
Not exact matches
This happens because the loss
of blood flow in a vessel causes the local oxygen level to drop, which stimulates local production
of vascular
endothelial growth factor, or VEGF, a protein which in most
tissues causes the growth
of new blood vessels to repair damage.
Epithelial cells form
tissue layers that cover our skin and the inner surfaces
of most
of our internal organs, while
endothelial cells line the adjacent blood - transporting vessels and capillaries that support their functions.
Current thinking regarding type III hypersensitivity is that immune cells within
tissues sense the presence
of these immune complexes (ICs) through specific receptor molecules and release inflammatory factors called cytokines that activate the
endothelial cells lining adjacent blood vessels to promote the recruitment
of neutrophils.
Using a powerful imaging technique that allowed the scientists to track the presence and movement
of parasites in living
tissues, the researchers found that Toxoplasma infects the brain's
endothelial cells, which line blood vessels, reproduces inside
of them, and then moves on to invade the central nervous system.
When zebrafish with the green fluorescing
endothelial gene matured, the researchers observed green FGPs on the surface
of the fish's brains — confirming that these cells arose from
endothelial tissue.
Researchers from the UNC School
of Medicine have discovered that cells called fibroblasts, which normally give rise to scar
tissue after a heart attack, can be turned into
endothelial cells, which generate blood vessels to supply oxygen and nutrients to the injured regions
of the heart, thus greatly reducing the damage done following heart attack.
The transplanted stem cells had differentiated into
endothelial cells — which form the inner lining
of a blood vessel, providing a barrier between blood and spinal cord
tissue — and attached to capillaries in the spinal cord.
Lymphocytes constantly circulate through blood vessels within lymph nodes and other lymphoid organs, but only some actually enter lymphoid
tissue by crossing the walls
of the vessels, known as high
endothelial venules (HEVs).
Key elements
of the immune system, they also have the ability to turn into several cell types after having passed the
endothelial barrier, in order to fulfil different functions depending on the
tissue.
Endothelial cells form the innermost layer
of the blood vessels - the endothelium - and have the function
of containing blood inside the vessels while allowing the passage
of nutrients to
tissues.
To overcome these limitations, we used two - color flow cytometry to identify and select microvascular
endothelial cells from primary cultures obtained from different organs
of mice whose
tissues harbor a temperature - sensitive SV40 large T antigen (H - 2Kb - tsA58 mice; ImmortoMice).
One
of the major impediments to obtaining a large number
of endothelial cells from different
tissues has been the inability to purify and propagate these cells in culture.
Tissue - specific microvascular
endothelial cell lines from H - 2K (b)- tsA58 mice for studies
of angiogenesis and metastasis
Three types
of structural variations were visible in the
tissue - specific
endothelial cell lines (Fig. 2) ⇓.
This happens because the loss
of blood flow in a blood vessel causes the local oxygen level to drop, which stimulates local production
of vascular
endothelial growth factor, or VEGF, a protein that in most
tissues causes the growth
of new blood vessels to repair damage.
In B,
endothelial cells from different
tissues were seeded at a density
of 1 × 105 cells / chamber in two - chamber slides and incubated with 10 mg / ml DiI - Ac - LDL in 10 % DMEM for 4 h. Cells were washed with label - free medium and fixed in 4 % paraformaldehyde.
Figure 2 shows sets
of results for four areas
of human corneal
endothelial tissue; central endothelium (defined by
endothelial cells within a 4 mm trephined boundary), central - intermediate endothelium (defined by
endothelial cells within an 8 mm trephined boundary), intermediate - peripheral endothelium (defined by
endothelial cells between the 4 mm trephine edge and 12 mm from the center
of the corneal endothelium), and the peripheral endothelium (defined by the 8 mm trephined edge and 12 mm from the center
of the corneal endothelium).
The fixed
tissues were covered on the
endothelial side with a 1:1000 dilution
of anti-BrdU primary antibody.
To obtain a viable donor
of a Descemet membrane endothelium disc, we modified the Descemet membrane stripping technique and monitored the percentage
of endothelial damage to the donor
tissue preparation.
For each assay, 200 μl
of sample (taken from the Optisol solution bathing the human and rabbit corneal
endothelial tissues) was added to microplates coated with TGF - β receptor.
Stimulation
of Transforming Growth Factor - ß1 - Induced
Endothelial - To - Mesenchymal Transition and
Tissue Fibrosis by Endothelin - 1 (ET - 1): A Novel Profibrotic Effect
of ET - 1.
We will combine methods from the fields
of immunology, developmental biology and angiogenesis to understand in vivo the development and lineage - specific function (s)
of resident macrophages, thereby opening new venues
of research into the interaction between macrophages and
endothelial cells in response to
tissue damage.
Isolation
of Endothelial Cells and Vascular Smooth Muscle Cells from Internal Mammary Artery
Tissue.
The postnatal adipose
tissue contains a heterogeneous population
of cells which includes adult stem cells (i.e., MSCs),
endothelial progenitor cells, leukocytes,
endothelial cells, and vascular smooth muscle cells.
Co-culture
of bone marrow fibroblasts and
endothelial cells on modified polycaprolactone substrates for enhanced potentials in bone
tissue engineering.
Unlike peripheral capillaries, which allow the relatively free exchange
of substances with the surrounding
tissue, the capillaries in the brain are tightly packed with
endothelial cells.
Expression and function
of the homeostatic molecule Del - 1 in
endothelial cells and the periodontal
tissue.
A team at the Harvard John A. Paulson School for Engineering and Applied Sciences (SEAS) and the Wyss Institute for Biologically Inspired Engineering at Harvard University has invented a method for 3D bioprinting thick vascularized
tissue constructs composed
of human stem cells, extracellular matrix, and circulatory channels lined with
endothelial blood vessel cells.
â $ œWe have solved a major obstacle
of using anti-miRNA as a therapeutic by being able to do a targeted delivery to only inflamed
endothelial cells while all other
tissues examined, including liver, lung, kidney, blood cells, spleen, etc showed no detectable side - effects, â $ Jo says.
Susan Amara, USA - «Regulation
of transporter function and trafficking by amphetamines, Structure - function relationships in excitatory amino acid transporters (EAATs), Modulation
of dopamine transporters (DAT) by GPCRs, Genetics and functional analyses
of human trace amine receptors» Tom I. Bonner, USA (Past Core Member)- Genomics, G protein coupled receptors Michel Bouvier, Canada - Molecular Pharmacology
of G protein - Coupled Receptors; Molecular mechanisms controlling the selectivity and efficacy
of GPCR signalling Thomas Burris, USA - Nuclear Receptor Pharmacology and Drug Discovery William A. Catterall, USA (Past Core Member)- The Molecular Basis
of Electrical Excitability Steven Charlton, UK - Molecular Pharmacology and Drug Discovery Moses Chao, USA - Mechanisms
of Neurotophin Receptor Signaling Mark Coles, UK - Cellular differentiation, human embryonic stem cells, stromal cells, haematopoietic stem cells, organogenesis, lymphoid microenvironments, develomental immunology Steven L. Colletti, USA Graham L Collingridge, UK Philippe Delerive, France - Metabolic Research (diabetes, obesity, non-alcoholic fatty liver, cardio - vascular diseases, nuclear hormone receptor, GPCRs, kinases) Sir Colin T. Dollery, UK (Founder and Past Core Member) Richard M. Eglen, UK Stephen M. Foord, UK David Gloriam, Denmark - GPCRs, databases, computational drug design, orphan recetpors Gillian Gray, UK Debbie Hay, New Zealand - G protein - coupled receptors, peptide receptors, CGRP, Amylin, Adrenomedullin, Migraine, Diabetes / obesity Allyn C. Howlett, USA Franz Hofmann, Germany - Voltage dependent calcium channels and the positive inotropic effect
of beta adrenergic stimulation; cardiovascular function
of cGMP protein kinase Yu Huang, Hong Kong -
Endothelial and Metabolic Dysfunction, and Novel Biomarkers in Diabetes, Hypertension, Dyslipidemia and Estrogen Deficiency, Endothelium - derived Contracting Factors in the Regulation
of Vascular Tone, Adipose
Tissue Regulation
of Vascular Function in Obesity, Diabetes and Hypertension, Pharmacological Characterization
of New Anti-diabetic and Anti-hypertensive Drugs, Hypotensive and antioxidant Actions
of Biologically Active Components
of Traditional Chinese Herbs and Natural Plants including Polypehnols and Ginsenosides Adriaan P. IJzerman, The Netherlands - G protein - coupled receptors; allosteric modulation; binding kinetics Michael F Jarvis, USA - Purines and Purinergic Receptors and Voltage-gated ion channel (sodium and calcium) pharmacology Pain mechanisms Research Reproducibility Bong - Kiun Kaang, Korea - G protein - coupled receptors; Glutamate receptors; Neuropsychiatric disorders Eamonn Kelly, Prof, UK - Molecular Pharmacology
of G protein - coupled receptors, in particular opioid receptors, regulation
of GPCRs by kinasis and arrestins Terry Kenakin, USA - Drug receptor pharmacodynamics, receptor theory Janos Kiss, Hungary - Neurodegenerative disorders, Alzheimer's disease Stefan Knapp, Germany - Rational design
of highly selective inhibitors (so call chemical probes) targeting protein kinases as well as protein interaction inhibitors
of the bromodomain family Andrew Knight, UK Chris Langmead, Australia - Drug discovery, GPCRs, neuroscience and analytical pharmacology Vincent Laudet, France (Past Core Member)- Evolution
of the Nuclear Receptor / Ligand couple Margaret R. MacLean, UK - Serotonin, endothelin, estrogen, microRNAs and pulmonary hyperten Neil Marrion, UK - Calcium - activated potassium channels, neuronal excitability Fiona Marshall, UK - GPCR molecular pharmacology, structure and drug discovery Alistair Mathie, UK - Ion channel structure, function and regulation, pain and the nervous system Ian McGrath, UK - Adrenoceptors; autonomic transmission; vascular pharmacology Graeme Milligan, UK - Structure, function and regulation
of G protein - coupled receptors Richard Neubig, USA (Past Core Member)- G protein signaling; academic drug discovery Stefan Offermanns, Germany - G protein - coupled receptors, vascular / metabolic signaling Richard Olsen, USA - Structure and function
of GABA - A receptors; mode
of action
of GABAergic drugs including general anesthetics and ethanol Jean - Philippe Pin, France (Past Core Member)- GPCR - mGLuR - GABAB - structure function relationship - pharmacology - biophysics Helgi Schiöth, Sweden David Searls, USA - Bioinformatics Graeme Semple, USA - GPCR Medicinal Chemistry Patrick M. Sexton, Australia - G protein - coupled receptors Roland Staal, USA - Microglia and neuroinflammation in neuropathic pain and neurological disorders Bart Staels, France - Nuclear receptor signaling in metabolic and cardiovascular diseases Katerina Tiligada, Greece - Immunopharmacology, histamine, histamine receptors, hypersensitivity, drug allergy, inflammation Georg Terstappen, Germany - Drug discovery for neurodegenerative diseases with a focus on AD Mary Vore, USA - Activity and regulation
of expression and function
of the ATP - binding cassette (ABC) transporters
For induction
of differentiation to mature
endothelial cells, EPCs were plated at a high cell density (8 × 104 cells / cm2) on
tissue culture treated flasks.
However, in this investigation no isoform
of p73 was found in
endothelial tissues.
Since stem cells have been found to be isolated at the peripheral / limbal region
of the epithelium [7 - 9], this study also investigates cell division potential in central and peripheral
endothelial tissue.
The
endothelial tissue from these samples was dissected and samples were analyzed for mRNA transcription
of p53, transactivating p63 (TAp63), delta N p63 (ΔNp63), transactivating p73 (TAp73), and delta N p73 (ΔNp73) via the reverse transcriptase - polymerase chain reaction (RT - PCR).
Samples
of central and peripheral human corneal
endothelial tissue were obtained as described above.
At the same time, the protein Vascular
Endothelial Growth Factor (VEGF) stimulates blood supply for the damaged
tissue, Fibroblast Growth Factor - 2 (FGF - 2) stimulates the damaged cells to grow and reproduce themselves, Transforming Growth Factor - beta (TGF - beta) stimulates cartilage to grow, and Stem Cell Factor (SCF) stimulates your native inactive stem cells to become activated and assist in the repair
of the damaged
tissue.
We will continue to explore Chrysalin's therapeutic value in
tissues and diseases exhibiting
endothelial dysfunction as well as the science behind and potential
of Chrysalin.