BRD4 protein appears to play key role in keeping stem cells in immature "pluripotent" state

Fuente: http://www.news-medical.net/news/20140926/BRD4-protein-appears-to-play-key-role-in-keeping-stem-cells-in-immature-pluripotent-state.aspx

A protein implicated in several cancers appears to play a pivotal role in keeping stem cells in an immature "pluripotent" state, according to a new study by NYU Langone Medical Center scientists. The study is published online in Cell Reports.

Stem cells are the perpetual adolescents of the cellular world, uncommitted to any cell fate. In principle, they can be programmed to differentiate into any mature cell type, holding the promise of regenerating tissues and organs. A fuller understanding of their biology, however, is needed.

"Our finding provides a better understanding of the complexity of how the stem cell state is regulated," says Eva M. Hernando-Monge, PhD, associate professor of pathology and a member of the Helen L. and Martin S. Kimmel Center for Stem Cell Biology at NYU Langone Medical Center.

The newly identified stem cell factor is BRD4, a protein associated with several cancers and the target of prospective therapies currently in clinical trials. In 2013, Dr. Hernando-Monge and colleagues found that BRD4 is overexpressed in melanoma cells and helps sustain their proliferation, whereas inhibiting BRD4 greatly slows their growth. The protein appeared to drive cancer in part by keeping cancer cells in a relatively immature, stem cell-like state. Intrigued, Dr. Hernando-Monge wanted to find out what role the protein played in actual stem cells.

In the new study, Dr. Hernando-Monge's team inhibited BRD4's activity in mouse and human embryonic stem cells using BRD4-blocking compounds developed by collaborator Ming-Ming Zhou and colleagues at the Icahn School of Medicine at Mount Sinai. They also used special RNA molecules that block BRD4 gene transcripts, and observed the cells shift out of the stem cell state. As they divided, the cells began to show characteristics of young neurons. Stem cells are thought to maintain a state of quiescence until some signal forces them to divide, producing a differentiated, highly specialized cell.

BRD4 has been known to regulate gene activity by binding to the support structure of DNA, called chromatin, at special switch sites called super-enhancers distributed throughout the genome. These sites are believed to be top-level controllers, orchestrating the distinctive expression patterns of several genes that together determine specific cell types such as nerve or muscle.

"We found that BRD4 occupies the super-enhancer sites of genes that are important for maintaining stem cell identity," says Raffaella Di Micco, PhD, a postdoctoral fellow who conceived the research project with Dr. Hernando-Monge and performed most of the experiments. These genes, including OCT4 and PRDM14, showed steep drops in expression when Dr. Di Micco applied BRD4 inhibitors to stem cells.

"OCT4 also represses neuronal differentiation, so we think that the loss of that repression with BRD4 inhibition is the most likely reason for the induction of neuronal characteristics in the stem cells," says Dr. Di Micco.

OCT4 is also one of the four factors in the standard "OKSM" cocktail used for turning ordinary cells into induced pluripotent stem cells (iPSCs). The new findings suggest that BRD4 enforces stem cell identity from an even higher regulatory level in the cell. "In theory we could replace one or more of those OKSM factors with BRD4, or add it to the cocktail to increase reprogramming efficiency—that's something we're working on now," says Dr. Hernando-Monge.

Conversely, she notes, BRD4 inhibitors could be used to help program cells in the other direction, turning stem cells into baby neurons, for example, which perhaps one day would be used for regenerative therapies.

Source: NYU Langone Medical Center

Un compuesto de la cúrcuma estimula la regeneración de las células madre del cerebro

Fuente: http://www.infosalus.com/nutricion/noticia-compuesto-curcuma-estimula-regeneracion-celulas-madre-cerebro-20140926093311.html

Un compuesto bioactivo que se encuentra en la cúrcuma promueve la proliferación y diferenciación de las células madre en el cerebro, según revela un nuevo estudio publicado en la revista de acceso abierto 'Stem Cell Research & Therapy'. Los hallazgos sugieren que la turmerona aromática podría ser un posible fármaco futuro para el tratamiento de trastornos neurológicos, como el ictus y la enfermedad de Alzheimer.

El estudio examinó los efectos de la turmerona aromática (ar-turmerona) sobre células madre endógenas neutras (NSC), que son las células madre que se encuentran dentro de los cerebros adultos. Las NSC se diferencian en neuronas y juegan un papel importante en la autorreparación y recuperación de la función cerebral en las enfermedades neurodegenerativas.

Estudios previos de este compuesto han demostrado que puede bloquear la activación de las células microgliales. Cuando se activan, estas células provocan neuroinflamación, que se asocia con diferentes trastornos neurológicos, pero se desconocía el impacto de la turmerona en la capacidad del cerebro de autorrepararse.

Investigadores del Instituto de Neurociencia y Medicina en Jülich, Alemania, estudiaron los efectos de la turmerona sobre la proliferación y diferenciación de NSC, tanto 'in vitro' como 'in vivo'. Cultivaron NSC de ratas fetales y las hicieron crecer en seis concentraciones diferentes de la turmerona aromática en un período de 72 horas.

En ciertas concentraciones, este compuesto demostró elevar la proliferación NSC hasta en un 80 por ciento, sin tener ningún impacto en la muerte celular. El proceso de diferenciación celular también se aceleró en las células tratadas con la turmerona frente a las que no fueron tratadas con el compuesto.

Para probar los efectos de la turmerona en las NSC in vivo, los investigadores inyectaron a ratas adultas con ar-turmerona y con imágenes de tomografía por emisión de positrones y un trazador para detectar las células proliferantes vieron que la zona subventricular (SVZ) era más ancha y el hipocampo se expandió en los cerebros de ratas inyectadas con ar-turmerona en comparación con los animales de control. La SVZ y el hipocampo son los dos sitios del cerebro de mamíferos adultos donde se sabe que se producen la neurogénesis y el crecimiento de las neuronas.

"Aunque se han descrito varias sustancias que promueven la proliferación de células madre en el cerebro, menos fármacos promueven también la diferenciación de células madre en neuronas, lo que constituye un objetivo importante en la medicina regenerativa. Nuestros hallazgos con la turmerona aromática nos acercan más a alcanzar este objetivo", subraya la autora principal del trabajo, Adele Rueger.

La ar-turmerona es el menos estudiado de los dos principales compuestos bioactivos que se encuentran en la cúrcuma. El otro compuesto es la curcumina, que es bien conocida por sus propiedades antiinflamatorias y neuroprotectoras.

With NIH grant, Cedars-Sinai helps bring big data to neuro disease research

Fuente: http://www.eurekalert.org/pub_releases/2014-09/cmc-wng092514.php

Cedars-Sinai Regenerative Medicine Institute will be part of 5-center consortium collecting and analyzing thousands of pieces of data to develop 'global' view of neuromuscular disorders.

Investigators at the Cedars-Sinai Board of Governors Regenerative Medicine Institute have received a grant from the National Institutes of Health to participate in a consortium taking the study of motor neuron disorders – such as Lou Gehrig's disease and spinal muscular atrophy – to a new, comprehensive perspective.

"We will be working as part of an NIH initiative to create databases of disease 'signatures' by generating and analyzing thousands of data points. Scientists often focus on very small things, such as a single signaling pathway in cells or a single gene or protein that is involved in some way with disease development, but identifying and correcting one component rarely leads to a cure. This is especially true in the brain because its networks are very complex," said Clive Svendsen, PhD, professor and director of the Board of Governors Regenerative Medicine Institute, principal investigator of Cedars-Sinai's part of the study.

Svendsen, the Kerry and Simone Vickar Family Foundation Distinguished Chair in Regenerative Medicine, compares this shift in perspective to the way meteorologists began predicting weather years ago – viewing global trends and collecting vast amounts of data to create a forecast for a specific place and time.

The grant is part of an NIH initiative called the Library of Integrated Network-based Cellular Signatures, or LINCS, program, which aims to develop a "library" of molecular signatures that describes how different cells respond to proteins, genes, chemicals – essentially anything that may come in contact with or change the cell or its activity.

Cedars-Sinai is a member of a group, NeuroLINCS, studying motor neuron disorders, which include Lou Gehrig's disease, also known as amyotrophic lateral sclerosis, or ALS, and spinal muscular atrophy. The NeuroLINCS study will be coordinated by researchers at the University of California, Irvine, with additional collaborators at the Gladstone Institutes at the University of California, San Francisco, Johns Hopkins University and the Broad Institute.

NeuroLINCS is one of six consortiums recently funded through NIH's LINCS program to study diabetes, cancers and other diseases using cell lines and specialized stem cells called induced pluripotent stem cells. Derived from a patient's own skin samples and "sent back in time" through genetic manipulation to an embryonic state, these cells can be made into any cell of the human body.

The Board of Governors Regenerative Medicine Institute, which has developed a national reputation for the quality of its induced pluripotent stem cells, was asked to provide the stem cells for all of the consortiums. The cells are produced in the Regenerative Medicine Institute's Induced Pluripotent Stem Cell Core Facility, directed by Dhruv Sareen, PhD, assistant professor of biomedical sciences and faculty research scientist with the Department of Biomedical Sciences.

Cedars-Sinai and the Regenerative Medicine Institute also will play a major role in the data generation phase of the study. New technology enables scientists to "mine" data on a large scale, such as measuring millions of proteins in a single sample – an area of expertise for Jennifer Van Eyk, PhD, director of Cedars-Sinai's Advanced Clinical Biosystems Research Institute and the Erika J. Glazer Chair in Women's Heart Health. She will be co-principal investigator of Cedars-Sinai's part of the study and will provide protein analysis for all NeuroLINCS collaborators. Other teams of experts will collect data on genetic material and the way genetic information is relayed to proteins within cells.

Svendsen said the data analysis teams will collaborate to create computer programs to pull all the information together.

"We may be looking at many thousands of data points, but using algorithms to create a 'cloud' of information, we expect to see a 'signature' emerge that shows us the relationships between proteins, genes and RNA in the cell. There will be a specific signature for healthy controls and a different one for the disease, such as Lou Gehrig's," Svendsen said. "Once we have that, we can try to 'punch holes' in the disease signature by hitting the cell with a small molecule to see how the cloud of information changes. The ultimate goal is to morph the disease cloud back into a healthy cloud. But right now, we don't know what the disease state is. This is what we want to find out."

At Cedars-Sinai, Svendsen and Sareen often collaborate on ALS and other motor neuron disease studies with Robert H. Baloh, MD, PhD, director of neuromuscular medicine and the ALS Program in the Department of Neurology.

"We have a strong mutual interest in developing personalized medicine for patients suffering from neurodegenerative diseases," Svendsen said. "We want to be able to create in a dish the motor neurons that mirror an individual patient's disease so we can see how quickly or slowly degeneration occurs. We also want to be able to interact with the disease model and see if we can slow it down in the dish. If so, theoretically, we should be able to slow it down in the patient as well. Through the LINCS grant, big data technology enables us to explore motor neurons in greater deal and gives us a much more sophisticated way of producing and analyzing these personalized models."

Conclusive evidence on role of circulating mesenchymal stem cells in organ injury

Fuente: http://www.eurekalert.org/pub_releases/2014-08/mali-ceo082114.php

Mesenchymal stem cells (MSCs) are present in virtually every type of human tissue and may help in organ regeneration after injury. But the theory that MSCs are released from the bone marrow into the blood stream following organ damage, and migrate to the site of injury, has long been debated. M.J. Hoogduijn and colleagues provide conclusive evidence to resolve the controversy over the mobilization and migration of MSCs in humans in a new study published in Stem Cells and Development, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. The article is available on the Stem Cells and Development website.

In "No Evidence for Circulating Mesenchymal Stem Cells in Patients with Organ Injury," Hoogduijn and coauthors from Erasmus University Medical Center (Rotterdam, The Netherlands), describe the results of studies to detect MSCs in the blood of healthy individuals, of patients with end-stage renal disease, of patients with end-stage liver disease, and of heart transplant patients with organ rejection. Whereas they did not find MSCs in the circulation of these individuals, they did report the presence of MSCs in the blood of a patient suffering from severe trauma with multiple fractures. In the trauma patient, the circulating MSCs likely derived from disruption of the bone marrow caused by the fractures.

"We can add the simple but elegant work of Martin Hoogduijn to the pantheon of studies in stem cell research that skewer a long treasured tenet of faith and consign it to mythology," says Editor-in-Chief Graham C. Parker, PhD, The Carman and Ann Adams Department of Pediatrics, Wayne State University School of Medicine, Detroit, MI.

Scientists identify rare stem cells that hold potential for infertility treatments

Fuente: http://medicalxpress.com/news/2014-09-scientists-rare-stem-cells-potential.html

First author Gina Aloisio, a student in UT Southwestern's Medical Scientist Training Program, and Dr. Diego H. Castrillon, Associate Professor of Pathology and Director of Investigative Pathology. 

Rare stem cells in testis that produce a biomarker protein called PAX7 help give rise to new sperm cells—and may hold a key to restoring fertility, research by scientists at UT Southwestern Medical Center suggests.

Researchers studying infertility in mouse models found that, unlike similar types of cells that develop into sperm, the stem cells that express PAX7 can survive treatment with toxic drugs and radiation. If the findings hold true in people, they eventually could lead to new strategies to restore or protect fertility in men undergoing cancer treatment.

"Unfortunately, many cancer treatments negatively impact fertility, and men who receive such treatments are at high risk of losing their fertility. This is of great concern among cancer patients," said Dr. Diego H. Castrillon, Associate Professor of Pathology and Director of Investigative Pathology. "The PAX7 stem cells we identified proved highly resistant to cancer treatments, suggesting that they may be the cells responsible for the recovery of fertility following such treatments."

Infertility, which the Centers for Disease Control estimates affects as many as 4.7 million men in the United States, is a key complication of cancer treatments, such as chemotherapy and radiation therapy.

The new findings, presented in the Journal of Clinical Investigation, provide valuable insight into the process of sperm development. Known as spermatogenesis, sperm development is driven by a population of "immature" stem cells called progenitors in the testes. These cells gradually "mature" into fully differentiated sperm cells. Dr. Castrillon and his team tracked progenitor cells that express the protein PAX7 in mouse testes, and found that these cells gradually give rise to mature sperm.

"We have long known that male fertility is driven by rare stem cells within the testes, but the precise identity of these stem cells has been disputed," said Dr. Castrillon, who holds the John H. Childers, M.D. Professorship in Pathology. "Our findings suggest that these rare PAX7 cells are the key cells within the testes that are ultimately responsible for male fertility." Importantly, even after exposure to toxic chemotherapy or radiation treatments, the PAX7-expressing cells continued to divide and thus could contribute to restoring sperm development.

Journal reference: Journal of Clinical Investigation

Suspect gene corrupts neural connections

Fuente: http://www.eurekalert.org/pub_releases/2014-08/niom-sgc081514.php

Researchers have long suspected that major mental disorders are genetically-rooted diseases of synapses – the connections between neurons. Now, investigators supported in part by the National Institutes of Health have demonstrated in patients' cells how a rare mutation in a suspect gene disrupts the turning on and off of dozens of other genes underlying these connections.

Synapses -- sites of intercellular communications -- are revealed in a mature iPSC cortex neuron derived from a participant in the study. Immune-based staining shows synapse markers (red, green) and the cell's nucleus (blue).

"Our results illustrate how genetic risk, abnormal brain development and synapse dysfunction can corrupt brain circuitry at the cellular level in complex psychiatric disorders," explained Hongjun Song, Ph.D., of Johns Hopkins University, Baltimore, a grantee of the NIH's National Institute of Mental Health (NIMH), a funder of the study.

Song and colleagues, from universities in the United States, China, and Japan, report on their discovery in the journal Nature.

"The approach used in this study serves as a model for linking genetic clues to brain development," said NIMH director Thomas R. Insel, M.D.

Most major mental disorders, such as schizophrenia, are thought to be caused by a complex interplay of multiple genes and environmental factors. However, studying rare cases of a single disease-linked gene that runs in a family can provide shortcuts to discovery. Decades ago, researchers traced a high prevalence of schizophrenia and other major mental disorders – which often overlap genetically – in a Scottish clan to mutations in the gene DISC1 (Disrupted In Schizophrenia-1). But until now, most of what's known about cellular effects of such DISC1 mutations has come from studies in the rodent brain.

To learn how human neurons are affected, Song's team used a disease-in-a-dish technology called induced pluripotent stem cells (iPSCs). A patient's skin cells are first induced to revert to stem cells. Stem cells play a critical role in development of the organism by transforming into the entire range of specialized cells which make up an adult. In this experiment, these particular "reverted" stem cells were coaxed to differentiate into neurons, which could be studied developing and interacting in a petri dish. This makes it possible to pinpoint, for example, how a particular patient's mutation might impair synapses. Song and colleagues studied iPSCs from four members of an American family affected by DISC1-linked schizophrenia and genetically related mental disorders.

Strikingly, iPSC-induced neurons, of a type found in front brain areas implicated in psychosis, expressed 80 percent less of the protein made by the DISC1 gene in family members with the mutation, compared to members without the mutation. These mutant neurons showed deficient cellular machinery for communicating with other neurons at synapses.

The researchers traced these deficits to errant expression of genes known to be involved in synaptic transmission, brain development, and key extensions of neurons where synapses are located. Among these abnormally expressed genes were 89 previously linked to schizophrenia, bipolar disorder, depression, and other major mental disorders. This was surprising, as DISC1's role as a hub that regulates expression of many genes implicated in mental disorders had not previously been appreciated, say the researchers.

The clincher came when researchers experimentally produced the synapse deficits by genetically engineering the DISC1 mutation into otherwise normal iPSC neurons – and, conversely, corrected the synapse deficits in DISC1 mutant iPSC neurons by genetically engineering a fully functional DISC1 gene into them. This established that the DISC1 mutation, was, indeed the cause of the deficits.

The results suggest a common disease mechanism in major mental illnesses that integrates genetic risk, aberrant neurodevelopment, and synapse dysfunction. The overall approach may hold promise for testing potential treatments to correct synaptic deficits, say the researchers.

###

Reference:

Wen Z, Nguyen HN, Guo Z, Lalli MA, Wang X, Su Y, Kim N-S, Yoon K-J, Shin J, Zhang C, Makri G, Nauen D, Yu H, Guzman E, Chiang C-H, Yoritomo N, Kaibuchi K, Zou J, Christian KM, Cheng L, Ross CA, Margolis RL, Chen G, Kosik KS, Song H, Ming G-l. Synaptic dysregulation in a human iPS cell model of major mental disorders. Nature, Aug. 17, 2014.

About the National Institute of Mental Health (NIMH): The mission of the NIMH is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery and cure. For more information, visit the NIMH website.

NINDS is the nation's leading funder of research on the brain and nervous system. The mission of NINDS is to seek fundamental knowledge about the brain and nervous system and to use that knowledge to reduce the burden of neurological disease.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

Researchers find that coronary arteries hold heart-regenerating cells

Fuente: http://medicalxpress.com/news/2014-08-coronary-arteries-heart-regenerating-cells.html

Endothelial cells residing in the coronary arteries can function as cardiac stem cells to produce new heart muscle tissue, Vanderbilt University investigators have discovered.


The findings, published recently in Cell Reports, offer insights into how the heart maintains itself and could lead to new strategies for repairing the heart when it fails after a heart attack.

The heart has long been considered to be an organ without regenerative potential, said Antonis Hatzopoulos, Ph.D., associate professor of Medicine and Cell and Developmental Biology.

"People thought that the same heart you had as a young child, you had as an old man or woman as well," he said.

Recent findings, however, have demonstrated that new heart muscle cells are generated at a low rate, suggesting the presence of cardiac stem cells. The source of these cells was unknown.

Hatzopoulos and colleagues postulated that the endothelial cells that line blood vessels might have the potential to generate new heart cells. They knew that endothelial cells give rise to other cell types, including blood cells, during development.

Now, using sophisticated technologies to "track" cells in a mouse model, they have demonstrated that endothelial cells in the coronary arteries generate new cardiac muscle cells in healthy hearts. They found two populations of cardiac stem cells in the coronary arteries – a quiescent population in the media layer and a proliferative population in the adventitia (outer) layer.

The finding that coronary arteries house a cardiac stem cell "niche" has interesting implications, Hatzopoulos said. Coronary artery disease – the No. 1 killer in the United States – would impact this niche.

"Our study suggests that coronary artery disease could lead to heart failure not only by blocking the arteries and causing heart attacks, but also by affecting the way the heart is maintained and regenerated," he said.

The current research follows a previous study in which Hatzopoulos and colleagues demonstrated that after a heart attack, endothelial cells give rise to the fibroblasts that generate scar tissue.

"It looks like the same endothelial system generates myocytes (muscle cells) during homeostasis and then switches to generate scar tissue after a myocardial infarction. After injury, regeneration turns to fibrosis," he said.

Understanding this switch could lead to new strategies for restoring regeneration and producing new heart muscle after a heart attack, during aging or in disease conditions such as diabetes and high blood pressure, he said.

"If we can understand the molecular mechanisms that regulate the fate switch that happens after injury, perhaps we can use some sort of chemical or drug to restore regeneration and make muscle instead of scar," Hatzopoulos said. "We think there is an opportunity here to improve the way we treat people who come into the clinic after myocardial infarction."

Journal reference: Cell Reports

The war on leukemia: How the battle for cell production could be decisive

Fuente: http://medicalxpress.com/news/2014-09-war-leukemia-cell-production-decisive.html

A key step in understanding the nature of the fight for superiority between mutated genes and normal genes could lead to new therapies to combat leukaemia, say researchers from the University of Birmingham and Newcastle University.

The study, published in Cell Reports, investigated Acute Myeloid Leukaemia to understand why leukemic cells are not able to develop normally into mature blood cells.

Stem cells in the bone marrow generate billions of different blood cells each day. The process resembles a production line with genes acting as regulators to control each step of the blood formation.

Leukaemia arises when the DNA encoding regulators in the stem cells is changed by a mutation. When a mutation occurs in the relevant regulator genes, the finely balanced order of the production line is disrupted with drastic consequences.

A chain reaction occurs, with the function of other regulators in the process being altered. The new cells no longer develop into normal blood cells, but leukemic cells that multiply and begin to take over the body.

Professor Constanze Bonifer, of the University of Birmingham, explained, "This particular leukaemia is characterised by a mutation in a gene that produces a rogue regulator. That is, one that is not normally made and behaves in a different way. The knock-on effect of that one mutation is huge."

The team showed that this aberrant regulator switches off hundreds of other genes, many of them regulators themselves, by using state of the art technology that looks at the activity of all genes within a cell. As a consequence of the drastically altered production line, normal blood formation cannot happen, and leukemic cells are formed.

Professor Bonifer added, "Understanding how these rogue regulators operate is essential. Because all cells contain two copies of each gene, one from the mother and one from the father, these leukemic cells have one mutated gene and one unchanged one that would make the normal regulator."

"What happens in the leukemic cell is fundamentally a battle for supremacy between the two regulators, and the mutated one wins much of the time. This is compounded by the normal regulator which tries to compensate for defeat, and in doing so changes the output of genes that would be otherwise unaffected by the abnormal regulator. Quite simply, the result is a real mess. The cells are confused and can't develop into mature blood cells."

Crucially, the team identified that removing the mutated regulator allowed the cells to resume their normal behaviour and the production line returns to the regular process.

Professor Olaf Heidenreich, of Newcastle University, said, "This one aberrant regulator reprograms thousands of genes. If targeting it can reverse the changes it is making to the cellular production line then it would ultimately point towards new avenues for a more precise treatment of leukaemia."

"Knowing that the production line can be restored to normal function gives us real hope. Of course, that is much easier to do in the lab that it is in the human body. But now we know how this works we can look to deliver inhibitors to those mutated regulators. Creating one that works is the next step we have to overcome."

Professor Heidenreich is leading on turning this breakthrough discovery into therapies that could provide new ways of combatting leukaemia.

Journal reference: Cell Reports

Stem cells have potential to repair diseased corneas

Fuente: http://medicalxpress.com/news/2014-09-stem-cells-potential-diseased-corneas.html

Corneal transplant (keratoplasty) is a known mean of successfully treating corneal disease. However, without unlimited donor corneas, researchers say there is a need to study alternate methods of treatment for eye disease and eye trauma.


One method being studied at the University of Cincinnati (UC) College of Medicine is the transplantation of human umbilical cord mesenchymal stem cells (UMSC) into the cornea stroma.

"We have previously shown that human UMSCs can survive the transplantation and we have now proved that UMSCs reduce inflammation; therefore the injured cornea cells have a chance to repair themselves," says Winston Kao, PhD, principal investigator on the research study, "Umbilical Cord Mesenchymal Stem Cells Suppress Host Rejection" which appears online in the Journal of Biological Chemistry.

Kao, a professor in UC's department of ophthalmology, says that UMSCs are one of the two types of umbilical cord stem cells that are extremely adaptable and have also been shown to repair bone and cartilage.

As Kao explains it, the UMSC cell is surrounded by a shield that is able to defend against antagonist cells that cause inflammation. In this study, a mouse model where human UMSCs were transplanted into diseased corneal stroma, the treated corneas went from cloudy to clear within a two-week period.

What isn't clear though is the mechanism by which these cells evade host rejection, says Kao, adding:

"The goal now is to analyze the shield and how the cells make it."

Because donor corneas are lessening—in part due to popular laser eye surgery that while restoring sight renders the cornea unusable for transplant—UMSC transplantation has potential as a treatment of both congenital and traumatic inflammatory eye diseases such as Fuchs' dystrophy or chemical burns.

More information: "Umbilical Cord Mesenchymal Stem Cells Suppress Host Rejection: THE ROLE OF THE GLYCOCALYX." Coulson-Thomas VJ, et al. J Biol Chem. 2014 Aug 22;289(34):23465-81. DOI: 10.1074/jbc.M114.557447. Epub 2014 Jul 1.

Journal reference: Journal of Biological Chemistry

Retrasar dos minutos el corte del cordón umbilical mejora el desarrollo del recién nacido

Fuente: http://www.agenciasinc.es/Noticias/Retrasar-dos-minutos-el-corte-del-cordon-umbilical-mejora-el-desarrollo-del-recien-nacido


Investigadores de la Universidad de Granada han demostrado que retrasar el corte del cordón umbilical de los recién nacidos dos minutos produce un mejor desarrollo del bebé durante los primeros días de su vida. Dicho retraso produjo un aumento en la capacidad antioxidante de los recién nacidos a término y la moderación de los efectos inflamatorios en el caso de los partos inducidos.

Un estudio realizado por científicos de la Universidad de Granada y el Hospital Clínico San Cecilio de Granada ha demostrado que retrasar el corte del cordón umbilical de los recién nacidos dos minutos produce un mejor desarrollo del bebé durante los primeros días de su vida.

Este trabajo multidisciplinar, publicado en la prestigiosa revista Pediatrics, revela que el tiempo de corte del cordón umbilical, también llamado clampaje del cordón, influye en la resistencia al estrés oxidativo de los neonatos.

Para la investigación, los expertos trabajaron con una muestra formada por 64 mujeres sanas embarazadas que dieron a luz en el Hospital Clínico San Cecilio de Granada. Todas ellas tuvieron un embarazo normal y un parto espontáneo vaginal.

A la mitad de los recién nacidos se les cortó el cordón umbilical a los 10 segundos, mientras que en la otra mitad esta operación se realizó de manera retrasada, a los dos minutos.

Los resultados obtenidos sugieren un efecto beneficioso del corte tardío del cordón umbilical, ya que produjo un aumento en la capacidad antioxidante de los recién nacidos a término y la moderación de los efectos inflamatorios en el caso de los partos inducidos.

Como explica Julio José Ochoa Herrera, autor principal de este estudio y profesor de la Universidad de Granada, el corte del cordón umbilical es una de las intervenciones más practicadas en los humanos y se tiene constancia de esta práctica quirúrgica desde hace siglos. Sin embargo, el tiempo de corte o clampaje del cordón umbilical es un tema controvertido, que presenta diferencias tanto para la madre como para el neonato.

La investigación compara por primera vez la influencia del tiempo de corte del cordón umbilical en el estrés oxidativo y la señal inflamatoria producida durante el parto tanto en la madre como en el neonato. “Nuestro estudio demuestra que el corte tardío ejerce un efecto beneficioso en la capacidad antioxidante y reduce la señal inflamatoria inducida durante el parto, lo cual podría mejorar el desarrollo postnatal durante los primeros días de vida”, concluye Ochoa.

Referencia bibliográfica:

Javier Díaz-Castro, Jesús Florido, Naroa Kajarabille, María Garrido-Sánchez, Carmen Padilla, Catalina de Paco, Luis Navarrete and Julio J. Ochoa. The Timing of Cord Clamping and Oxidative Stress in Term Newborns. Pediatrics 2014;134;257; DOI: 10.1542/peds.2013-3798