La Universidad Carlos III, la Fundación Jiménez Díaz y el CIEMAT crean una Cátedra de Medicina Regenerativa y Bioingeniería de Tejidos

Fuente: http://noticias.lainformacion.com/salud/genetica/la-carlos-iii-la-jimenez-diaz-y-el-ciemat-crean-una-catedra-de-medicina-regenerativa-y-bioingenieria-de-tejidos_1OtLuqTXq9Sv4SrLdz7Cu4/

La Universidad Carlos III de Madrid (UC3M), el Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz (IISFJD) y el Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT) han suscrito un convenio de colaboración para la creación de la Cátedra FJD de Medicina Regenerativa y Bioingeniería de Tejidos que busca impulsar la investigación biomédica y el desarrollo de terapias innovadoras.

La nueva cátedra nace con el objetivo de potenciar la investigación biomédica de patologías que no cuentan con tratamientos adecuados, sobre todo en el área de las genodermatosis y otras dolencias cutáneas, además de desarrollar terapias innovadoras que puedan ser objeto de estudios/ensayos clínicos con pacientes, ha informado la institución en un comunicado.

La cátedra persigue también constituir un equipo de investigación que sea capaz de generar tecnologías terapéuticas innovadoras a nivel nacional e internacional, desarrollar productos de base biotecnológica que puedan beneficiar a los pacientes, fomentar tesis doctorales centradas en este campo y hacer también una labor de divulgación científica en congresos científicos y entre el público en general.

La dirección de la Cátedra correrá a cargo de la profesora Marcela del Río Nechaevsky, del departamento de Bioingeniería de la UC3M y de la Unidad de Medicina Regenerativa CIEMAT-CIBER de Enfermedades Raras.

Entre las actividades a desarrollar al amparo de esta Cátedra figuran la caracterización clínica, fisiopatológica, celular y genética de las genodermatosis (enfermedades cutáneas de origen genético); el empleo de células madre adultas (mesenquimales y epiteliales) en regeneración cutánea; y la utilización de matrices 3D portadoras de células madre adultas para el desarrollo de modelos de investigación humanizados y su aplicación en estudios preclínicos.

Desde la cátedra, que engloba por el momento a una veintena de investigadores, se trabajará también en el ámbito de la terapia génica mediante el empleo de células madre adultas modificadas genéticamente en dos líneas: para su uso como biorreactores de factores con actividad biológica y para la corrección del fenotipo patológico en genodermatosis.

A juicio de la directora de la cátedra, Marcela del Río Nechaevsky, esta iniciativa permitirá "realizar una investigación de calidad y fomentar su traslación en beneficio de los pacientes".

El objetivo es conseguir resultados preclínicos que permitan a medio plazo una traslación efectiva a la práctica médica.

Tras la firma del convenio el presidente del Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz, Juan Antonio Álvaro de la Parra, ha considerado que "esta cátedra permitirá trasladar a la sociedad, todo el conocimiento generado en este equipo investigador".

El rector de la UC3M, Daniel Peña Sánchez de Rivera, ha señalado que esta cátedra reúne los elementos por los que trabajan cada día en la UC3M y por los que quieren que se les reconozca: "la investigación más avanzada e innovadora, equipos humanos sobresalientes y de reconocido prestigio y el servicio a la sociedad, en este caso, a través de la atención a pacientes de estas y otras enfermedades".

Por último, el director general del CIEMAT, Cayetano López Martínez, ha destacado "su satisfacción por la firma de este acuerdo, gracias al cual el trabajo desarrollado con tanta dedicación como solvencia en los laboratorios podrá ser puesto en valor en la práctica clínica.

La sociedad espera retornos del esfuerzo hecho en investigación, en este caso herramientas útiles para atender a la salud de los ciudadanos en patologías de difícil tratamiento sin el bagaje de conocimientos acumulado previamente en la investigación pre-clínica".

Mount Sinai researchers awarded grant to find new stem cell therapies for vision recovery

Fuente: http://www.eurekalert.org/pub_releases/2014-11/tmsh-msr112014.php

The National Eye Institute (NEI), a division of the National Institutes of Health, has awarded researchers at the Icahn School of Medicine at Mount Sinai a five-year grant totaling $1 million that will support an effort to re-create a patients' ocular stem cells and restore vision in those blinded by corneal disease.

About six million people worldwide have been blinded by burns, trauma, infection, genetic diseases, and chronic inflammation that result in corneal stem cell death and corneal scarring.

There are currently no treatments for related vision loss that are effective over the long term. Corneal stem cell transplantation is an option in the short term, but availability of donor corneas is limited, and patients must take medications that suppress their immune systems for the rest of their lives to prevent rejection of the transplanted tissue.

A newer proposed treatment option is the replacement of corneal stem cells to restore vision. The grant from the NEI will fund Mount Sinai research to re-create a patient's own stem cells and restore vision in those blinded by corneal disease. Technological advances in recent years have enabled researchers to take mature cells, in this case eyelid or oral skin cells, and coax them backward along the development pathways to become stem cells again. These eye-specific stem cells would then be redirected down pathways that become needed replacements for damaged cells in the cornea, in theory restoring vision.

"Our findings will allow the creation of transplantable eye tissue that can restore the ocular surface," said Albert Y. Wu, MD, PhD, Assistant Professor, Department of Ophthalmology at the Icahn School of Medicine at Mount Sinai and principle investigator for the grant-funded effort. "In the future, we will be able to re-create a patient's own corneal stem cells to restore vision after being blind," added Dr. Wu, also Director of the Ophthalmic Plastic and Reconstructive Surgery, Stem Cell and Regenerative Medicine Laboratory in the Department of Ophthalmology and a member of the Black Family Stem Cell Institute at Icahn School of Medicine. "Since the stem cells are their own, patient's will not require immunosuppressive drugs, which would greatly improve their quality of life."

Specifically, the grant will support efforts to discover new stem cell therapies for ocular surface disease and make regenerative medicine a reality for people who have lost their vision. The research team will investigate the most viable stem cell sources, seek to create ocular stem cells from eyelid or oral skin cells, explore the molecular pathways involved in ocular and orbital development, and develop cutting-edge biomaterials to engraft a patient's own stem cells and restore vision.

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Other investigators from Mount Sinai include Ihor Lemischka, PhD, Director, Black Family Stem Cell Institute and J. Mario Wolosin, PhD, Professor of Ophthalmology. The research is supported by NEI grant EY023997.

Nueva información sobre la replicación genética podría ayudar en la lucha contra el cáncer

Fuente: http://noticias.lainformacion.com/salud/genetica/nueva-informacion-sobre-la-replicacion-genetica-podria-ayudar-en-la-lucha-contra-el-cancer_UpaMPTwU7nE498KvPMUnz6/

Una nueva línea de investigación de un equipo de la Universidad del Estado de Florida, en Estados Unidos, está ampliando la información sobre cómo se replica el material genético humano y qué significa para las personas con enfermedades en las que se interrumpe ese proceso, como por ejemplo, en el cáncer.

Nueva información sobre la replicación genética podría ayudar en la lucha contra el cáncer

El equipo, dirigido por el profesor del Departamento de Ciencias Biológicas David Gilbert y el investigador post-doctoral Ben Pope, ha analizado en profundidad la forma en la que el ADN y el material genético asociado se replican y organizan dentro del núcleo de una célula.

El documento, que se publica en la edición de la revista 'Nature', arroja luz sobre un tema que ha sido poco estudiado por los investigadores de todo el mundo y que es de gran interés debido a los avances futuros que se pueden lograr con estos hallazgos.

El informe de Pope y Gilbert es una pieza dentro de un gran proyecto multiinstitucional llamado ENCODE, financiado por los Institutos Nacionales de Salud de Estados Unidos. Este esfuerzo multiinstitucional se centró en una revisión integral del genoma del ratón y encontró muchas similitudes y diferencias con el genoma humano.

Además de su propio trabajo en la replicación del ADN, estos científicos también figuran como contribuyentes a la pieza de ENCODE, un esfuerzo puesto en marcha en 2007 para construir un catálogo completo de los elementos funcionales del genoma del ratón y que complementa el anterior proyecto ENCODE humano, cuyo catálogo funcional se hizo público en 2012.

En su informe, Pope y Gilbert examinaron el proceso de replicación en detalle para poder identificar las unidades por las cuales el material genético se replica porque sabían que sucede a intervalos regulares, pero necesitaban conocer dónde están los límites.

"El primer paso fundamental en la comprensión de un fenómeno nuevo en la naturaleza es identificar las unidades de regulación y, por fin, lo tenemos", celebra Gilbert. Los científicos creen que la investigación continua en esta área podría dar lugar a nuevas opciones de tratamiento para pacientes con cáncer y aquellos que podrían beneficiarse de terapias basadas en células madre.

"El proceso está bien conservado en muchas especies, lo que sugiere que es crítico -subraya Pope-- pero realmente no sé por qué. Más investigación nos ayudará a entender por qué este proceso se interrumpe en el cáncer y otras enfermedades".

Por otra parte, la revisión integral del genoma del ratón reveló que un número importante de los genes del ratón no se comportan igual que sus homólogos humanos, lo que sugiere que la ciencia se trendrá que replantear al menos algunas funciones del ratón de laboratorio como organismo modelo.

Durante más de un siglo, el ratón de laboratorio ('Mus musculus') se ha empleado en experimentos que van desde descifrar la enfermedad y la función cerebral a explicar los comportamientos sociales y la naturaleza de la obesidad. El pequeño roedor ha demostrado ser una herramienta biológica indispensable, la base de décadas de profundo descubrimiento científico y progreso médico.

"La suposición ha sido durante mucho tiempo que todo lo que era descubierto en el ratón probablemente sería cierto también en los seres humanos, pero nunca se había evaluado esta idea de forma sistemática", señala Bing Ren, profesor en el Departamento de Medicina Celular y Molecular, líder del Laboratorio de Regulación Génica del Instituto Ludwig para la Investigación del Cáncer de la Universidad de California San Diego, en Estados Unidos, y uno de los autores principales de esta investigación.

"Sabemos ahora que esta suposición no es del todo cierta. Hay un número importante de genes de ratón que son regulados de manera diferente que genes similares en los seres humanos. Las diferencias no son al azar", afirma este experto, cuyos hallazgos son parte de una serie de documentos relacionados que se publican juntos en 'Nature', 'Science' y 'Genome Research' y que se derivan del proyecto ENCODE.

Research team proves the efficacy of new drug against stem cells that provoke the onset and growth of cancer and its metastasis

Fuente: http://canalugr.es/health-science-and-technology/item/74924-research-team-proves-the-efficacy-of-new-drug-against-stem-cells-that-provoke-the-onset-and-growth-of-cancer-and-its-metastasis

An Andalusian team of researchers led by the University of Granada has designed a drug that fights cancerogenic stem cells responsible for the onset and development of cancer, for relapse after chemotherapy, and for metastasis.

The new drug, called Bozepinib, has been successfully tested in mice, and has a selective action against cancerogenic stem cells for breast and colon cancer, as well as melanoma.

An Andalusian team of researchers led by the University of Granada has demonstrated the efficacy of a new drug against cancerogenic stem cells, which cause the onset and development of cancer, of relapse after chemotherapy and metastasis. This drug, called Bozepinib, has proved to be effective in tests with mice. The results have been published in the prestigious journal Oncotarget.

Cancerogenic stem cells appear in small quantities in tumours, and one of their important features is that they contribute to the formation of metastasis in different places within the original tumour. Cancerogenic stem cells remain dormant under normal conditions (i.e. they do not divide). Conventional chemotherapy and radiotherapy act upon those cancer cells which are clearly differentiated—i.e. which are undergoing processes of division—but they cannot destroy these dormant cancerogenic stem cells. Actually, after a positive initial response to treatment, many cancer patients suffer a relapse because these cancerogenic stem cells have not been destroyed.

During the last few years, research in fight against cancer has focused on the search for new drugs that can selectively attack these cancerogenic stem cells. If they can be eliminated, the tumour will then be eliminated in its entirety, which will lead to the complete curation of patients.

Scientists in the “Advanced therapies: differentiation, regeneration and cancer” research group led by UGR professor Juan Antonio Marchal have collaborated with Joaquín Campos, from the School of Pharmacy, U. of Granada, and María Ángeles García, from Virgen de las Nieves University Hospital in Granada, as well as with the universities of Jaen and Miami (US) to develop the new drug Bozepinib.

This new drug shows a selective type of activity against cancerogenic stem cells in breast, colon, and skin cancers. “The powerful anti-tumour activity of Bozepinib is due to the inhibition of the HER2 signalling pathway, and to the fact that this drug inhibits the invasiveness and the formation of new vessels in the tumour (angiogenesis)”, says prof. Juan Antonio Marchal. Researchers have also revealed the specific mechanism by means of which Bozepinib acts against cancerogenic stem cells.

This new drug proved to be nontoxic for healthy mice when it was intraperitoneally or orally administered, and it also inhibited tumoural growth and the formation of lung metastasis in those mice in which the tumour was induced.

Researchers are currently conducting safety tests and they expect that this new drug, as well as its derivatives, can be run through clinical tests with actual patients in the near future.

Bibliography:

HER2-signaling pathway, JNK and ERKs kinases, and cancer stem-like cells are targets of Bozepinib

Alberto Ramírez, Houria Boulaiz, Cynthia Morata-Tarifa, Macarena Perán, Gema Jiménez, Manuel Picon-Ruiz, Ahmad Agil, Olga Cruz-López, Ana Conejo-García, Joaquín M. Campos, Ana Sánchez, María A. García, Juan A. Marchal

Oncotarget, Vol. 5, No. 11

The article can be downloaded from the following link:

http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path[]=1962

Picture 1: The authors of this research project. Left to right (front row): Cynthia Morata, Gema Jiménez; (back row): Macarena Perán, Juan Antonio Marchal, Alberto Ramírez, Houria Boulaiz, María Ángel García.

Picture 2: Cancerogenic stem cells

Picture 3: Histological section cutting of a primary tumour before and after treatment with Bozepinib.

Contact:

Juan Antonio Marchal Corrales

Centre for Biomedical Research / Department of Human Anatomy and Embryology, University of Granada

Phone: 958 249 321

Email: jmarchal@ugr.es

Stem cell researcher pioneers gene therapy cure for children with "bubble baby" disease

Fuente: http://medicalxpress.com/news/2014-11-stem-cell-gene-therapy-children.html

UCLA stem cell researchers have pioneered a stem cell gene therapy cure for children born with adenosine deaminase (ADA)-deficient severe combined immunodeficiency (SCID), often called "bubble baby" disease, a life-threatening condition that if left untreated can be fatal within the first year of life.

The groundbreaking treatment was developed by renowned stem cell researcher and UCLA Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research member Dr. Donald Kohn, whose breakthrough was developed over three decades of research to create a gene therapy that safely restores immune systems in children with ADA-deficient SCID using the patient's own cells with no side effects.

To date, 18 children with SCID have been cured of the disease after receiving the stem cell gene therapy in clinical trials at UCLA and the National Institutes of Health.

"All of the children with SCID that I have treated in these stem cell clinical trials would have died in a year or less without this gene therapy, instead they are all thriving with fully functioning immune systems" said Kohn, a professor of pediatrics and of microbiology, immunology and molecular genetics in Life Sciences.

To protect children born with SCID they are kept in isolation, in controlled environments because without an immune system they are extremely vulnerable to illness and infection that could be lethal.

"Other current options for treating ADA-deficient SCID are not always optimal or feasible for many children," said Kohn. "We can now, for the first time, offer these children and their families a cure, and the chance to live a full healthy life."

Children born with SCID, an inherited immunodeficiency, are generally diagnosed at about six months. They are extremely vulnerable to infectious diseases, and in a child with ADA-deficient SCID even the common cold can prove fatal. The disease causes cells to not create an enzyme called ADA, which is critical for production of the healthy white blood cells that drive a normal, fully-functioning immune system. About 15 percent of all SCID patients are ADA-deficient.

Currently, the only treatments for these children include injecting them twice a week with the necessary enzyme, a life-long process that is very expensive and often doesn't return the immune system to optimal levels. These children also have the option to undergo bone marrow transplants from matched siblings, but matches are very rare or result in rejection of the transplanted cells which then turn against the child.

Since 2009 and over the course of a two multi-year clinical trials, Kohn and his team tested two therapy regimens on 18 children with ADA-deficient SCID. During the trials, the patient's blood stem cells were removed from their bone marrow and genetically modified to correct the defect. All of the 18 patients were cured.

Kohn used a virus delivery system that he first developed in his lab in the 1990s to insert the corrected gene that produces the missing enzyme necessary for a healthy immune system into the blood forming stem cells in the bone marrow. The genetically corrected blood forming stem cells then produce T cells that will fight infection.

He and colleagues tested different viral vectors, modifying each and perfecting viral delivery as the best method to put the healthy ADA genes back into the bone marrow cells of the patients. With the newly-transplanted cells now able to produce the needed enzyme, they use the powerful self-renewal potential of stem cells to repopulate the blood stream and the child develops their own new, fully-functioning immune system.

"We were very happy that over the course of several clinical trials and after making refinements and improvements to the treatment protocol, we are now able to provide a cure for babies with this devastating disease using the child's own cells," said Kohn.

The next step is to seek FDA approval for the gene therapy in the hopes that all children with ADA-deficient SCID will be able to benefit from the treatment.

This cutting-edge research also lays the groundwork for the successful gene therapy to be clinically tested for treatment of sickle cell disease, with trials set to begin next year.

"We've been working for the last five years to take the success we've had with this stem cell gene therapy for SCID to sickle cell," said Kohn. "We now have the potential to take the gene that blocks sickling and get it into enough of a patient's stem cells to block the disease."

The Padilla-Vaccaro Family: One Child's Story

Only weeks after giving birth to fraternal twins in 2012, Alysia Padilla-Vaccaro quickly felt something was wrong with one of her daughters, Evangelina, now two years old.

"I was told that it was the stress, or the fear of being a new mom, but I just knew something wasn't right," said Padilla-Vaccaro. "Then I was informed that Evangelina had absolutely no immune system. That anything that could make her sick, would kill her. It was literally the worst time of my life."

Alysia and her husband Christian, of Corona, California, brought Evangelina to see Dr. Kohn at UCLA. Soon after undergoing Dr. Kohn's stem cell gene therapy treatment, Evangelina's new immune system developed without side effects. Her T cell count began to rise and her ability to fight off illness and infection grew stronger.

Then Dr. Kohn told Alysia and Christian the good news. For the first time, they could hug and kiss their daughter and take Evangelina outside to meet the world.

"To finally kiss your child on the lips, to hold her, it's impossible to describe what a gift that is," Padilla-Vaccaro said. "I gave birth to my daughter, but Dr. Kohn gave my baby life."

Reprogramming 'support cells' into neurons could repair injured adult brains

Fuente: http://medicalxpress.com/news/2014-11-reprogramming-cells-neurons-adult-brains.html

This is a scanning electron micrograph (false color) of a human induced pluripotent stem cell-derived neuron.

The portion of the adult brain responsible for complex thought, known as the cerebral cortex, lacks the ability to replace neurons that die as a result of Alzheimer's disease, stroke, and other devastating diseases. A study in the International Society for Stem Cell Research's journal Stem Cell Reports, published by Cell Press, shows that a Sox2 protein, alone or in combination with another protein, Ascl1, can cause nonneuronal cells, called NG2 glia, to turn into neurons in the injured cerebral cortex of adult mice. The findings reveal that NG2 glia represent a promising target for neuronal cell replacement strategies to treat traumatic brain injury.

"Our study is the first to demonstrates unambiguously the conversion of a specific subtype of glia, the so-called NG2 glia, into induced neurons in living animals," says senior study author Benedikt Berninger of Johannes Gutenberg University Mainz. "The findings pave the way for future studies aimed at harnessing the potential of these cells for brain repair."

The cerebral cortex plays a key role in memory, attention, perception, language, and consciousness. Unlike other regions in the adult brain, the cerebral cortex is not capable of generating new neurons after traumatic injury. Berninger and others have previously shown that Sox2, Ascl1, and other transcription factors—proteins that bind to specific DNA sequences to control the activity of genes—can induce the nonneuronal "support cells" known as glia to turn into neurons. It has been difficult, however, to convert glia into neurons after brain injuries such as stroke in the adult cerebral cortex of living animals.

To test potential brain repair strategies, Berninger and Magdalena Götz of Ludwig-Maximilians University Munich delivered transcription factors into the cerebral cortex of adult mice three days after traumatic injury. Surprisingly, they found that Sox2 alone or in combination with Ascl1 was sufficient to trigger the emergence of neurons, contrary to the widely accepted view that Sox2 prevents stem cells from turning into more mature cells such as neurons. Notably, the majority of cells that converted into neurons were NG2 glia. These glial cells have received relatively little attention in the past, even though they represent a promising cellular source for brain repair strategies because of their abundance and life-long capacity for proliferation.

Taken together, these findings support the notion that cellular reprogramming may become a way of replacing degenerated neurons in the adult brain. "Our study sets the stage for further research to identify which additional cues could induce these neurons to fully mature and incorporate into functional circuits, thereby allowing this approach to potentially be used in the clinic," Berninger says.

More information: Stem Cell Reports, Heinrich et al.: "Sox2-mediated conversion of NG2 glia into induced neurons in the injured adult cerebral cortex" www.cell.com/stem-cell-reports… 2213-6711(14)00329-4

The cellular origin of fibrosis: Team identifies rare stem cells that give rise to chronic tissue scarring

Fuente: http://medicalxpress.com/news/2014-11-cellular-fibrosis-team-rare-stem.html

Rare stem cells (in red) that give rise to scar-tissue secreting myofibroblast cells, here found near the blood vessels of a mouse kidney (in green). 

Harvard Stem Cell Institute scientists at Brigham and Women's Hospital have found the cellular origin of the tissue scarring caused by organ damage associated with diabetes, lung disease, high blood pressure, kidney disease, and other conditions. The buildup of scar tissue is known as fibrosis.

Fibrosis has a number of consequences, including inflammation, and reduced blood and oxygen delivery to the organ. In the long term, the scar tissue can lead to organ failure and eventually death. It is estimated that fibrosis contributes to 45 percent of all deaths in the developed world.

The researchers, led by Benjamin Humphreys, MD, PhD, found that a rare population of stem cells located outside of blood vessels in mice become myofibroblast cells that secrete proteins that cause scar tissue.

Killing these stem cells prevents the deadly complications of fibrosis, the researchers report in the journal Cell Stem Cell online. Rafael Kramann, MD, a postdoctoral fellow in Humphreys' lab, is the first author on the paper.

"Under normal circumstances, myofibroblasts stimulate wound healing, but when there's an ongoing injury to an organ (e.g., the liver of a hepatitis C patient, the heart of a patient with high blood pressure, or the kidney of a patient with diabetes) these proteins clog up normal functioning," said Humphreys, a Harvard Medical School associate professor at Brigham and Women's Hospital, who leads the Harvard Stem Cell Institute Kidney Program.

The researchers are now in discussions with a pharmaceutical firm about screening for drugs that might target and shut off these fibrosis-causing stem cells in cases of chronic organ disease. The idea of using the stem cells as targets for drug discovery began with the formation by Humphreys, Kramann, and Derek DiRocco, PhD, of MatriTarg Laboratories—the 2013 Harvard Dean's Health and Life Sciences Challenge winning startup.

"We wanted to know if eradication of this very small population of stem cells would improve organ function, and both kidney and heart were completely protected from developing fibrosis-related complications (e.g., kidney failure and heart failure)," said Humphreys, who also heads the Onco-Nephrology Program at the Dana-Farber Cancer Institute. "This provides an important proof of principal that drugs that target the stem cells could be therapeutic."

The cellular origin of kidney fibrosis has long puzzled researchers. It was unknown which kinds of stem cells form myofibroblasts, and where these stem cells are located. One long-held hypothesis was that the stem cells that give rise to myofibroblasts are found in the bone marrow, but Humphreys' research disproves that. By tagging a specific protein called Gli1 expressed by the myofibroblast-forming stem cells, the scientists showed that the cells are found on the periphery of blood vessels and they also reside within organs.

Humphreys does caution that the cell population his lab found is responsible for about 60 percent of all organ myofibroblasts, which means that they seem to be the most dominant source, but that there may be other cells that also contribute to the myofibroblast population.

"We haven't disproven every hypothesis and our results do leave room for other cells that might contribute to fibrosis," he said.

The Humphreys Lab collaborated with fellow Harvard Stem Cell Institute member Benjamin Ebert, MD, also at Brigham and Women's Hospital, on the work.

More information: Humphreys, B. D., and Kramann, R. et al. Perivascular Gli1+ progenitors are key contributors to injury-induced organ fibrosis. Cell Stem Cell. January 8, 2015. Advanced online publication November 18, 2014. DOI: 10.1016/j.stem.2014.11.004

Consiguen ralentizar el avance del mieloma múltiple en personas mayores

Fuente: http://noticias.lainformacion.com/salud/enfermedades/consiguen-ralentizar-el-avance-del-mieloma-multiple-en-personas-mayores_baNkNLmY7TWDyYu6FThIh2/

Un ensayo internacional en el que ha participado el Instituto de Investigación contra la Leucemia Josep Carreras (IJC) ha conseguido mejorar el tratamiento y frenar el avance de los mielomas múltiples en personas de edad avanzada que no pueden ser sometidas a un trasplante de médula ósea.

La investigación, que publica la revista New England Journal of Medicine, se ha llevado a cabo con 1.623 pacientes enfermos de mieloma múltiple en 246 centros de tratamiento de 18 países.

Una parte de estos pacientes han sido diagnosticados y tratados en el Instituto Catalán de Oncología (ICO) y en el Hospital Germans Trias i Pujol(Can Ruti) de Badalona por el doctor Albert Oriol, que es investigador del IJC.

Según ha informado la Fundación Josep Carreras, los pacientes participantes en este ensayo fueron divididos en tres grupos al azar.

El primero recibió una combinación de lenalidomida y dexametasona en ciclos de 28 días hasta la progresión de la enfermedad, el segundo grupo se sometió al mismo tratamiento durante 72 semanas (18 ciclos) y el tercer grupo recibió el tratamiento estándar (melfalan-prednisona y talidomida MPT) en 42 ciclos de día durante 72 semanas.

Los médicos comprobaron que los pacientes que recibieron de forma continua la combinación de lenalidomida y dexametasona vivieron más tiempo sin que la enfermedad progresase, una media de 25,5 meses, en comparación con los 20,7 meses de los que recibieron 18 ciclos y 21,2 meses de los enfermos tratados con el tratamiento estándar.

Según la Fundación Josep Carreras, los resultados de este estudio dan más esperanza a los pacientes de mieloma múltiple, un tipo de cáncer de médula ósea que afecta a las células plasmáticas y que suele aparecer predominantemente en personas de edad avanzada. La media de edad es de 65 años.

Actualmente, ninguno de los procedimientos quimioterápicos cura esta enfermedad, que sólo se puede sanar mediante un trasplante alogénico de progenitores hemopoyéticos, aunque la elevada edad de la mayoría de los pacientes y la gran toxicidad del procedimiento hace que se pueda emplear en contadas ocasiones.

Aunque los resultados han sido positivos, los autores han recomendado más estudios para analizar la supervivencia global en un período más largo sabiendo que la terapia con lenalidomida y dexametasona es una buena opción.

Por otra parte, investigadores del IJC también han participado en la identificación por primera vez de un mecanismo celular por el cual se forma un tipo de síndrome mielodisplástico, un descubrimiento que podría ser utilizado en un futuro para desarrollar una posible terapia de esta enfermedad.

Bajo la denominación de síndromes mielodisplásticos se incluyen enfermedades que tienen como característica común que las células madre de la médula ósea, encargadas de fabricar todas las células de la sangre, tienen un defecto que las hace producir células anómalas y en menor cantidad de lo normal, lo que acaba degenerando en una leucemia mieloide aguda.

Cardiac stem cell therapy may heal heart damage caused by Duchenne muscular dystrophy

Fuente: http://medicalxpress.com/news/2014-11-cardiac-stem-cell-therapy-heart.html

Researchers at the Cedars-Sinai Heart Institute have found that injections of cardiac stem cells might help reverse heart damage caused by Duchenne muscular dystrophy, potentially resulting in a longer life expectancy for patients with the chronic muscle-wasting disease.

The study results were presented at a Breaking Basic Science presentation during the American Heart Association Scientific Sessions in Chicago. After laboratory mice with Duchenne muscular dystrophy were infused with cardiac stem cells, the mice showed steady, marked improvement in heart function and increased exercise capacity.

Duchenne muscular dystrophy, which affects 1 in 3,600 boys, is a neuromuscular disease caused by a shortage of a protein called dystrophin, leading to progressive muscle weakness. Most Duchenne patients lose their ability to walk by age 12. Average life expectancy is about 25. The cause of death often is heart failure because the dystrophin deficiency leads to cardiomyopathy, a weakness of the heart muscle that makes the heart less able to pump blood and maintain a regular rhythm.

"Most research into treatments for Duchenne muscular dystrophy patients has focused on the skeletal muscle aspects of the disease, but more often than not, the cause of death has been the heart failure that affects Duchenne patients," said Eduardo Marbán, MD, PhD, director of the Cedars-Sinai Heart Institute and study leader. "Currently, there is no treatment to address the loss of functional heart muscle in these patients."

During the past five years, the Cedars-Sinai Heart Institute has become a world leader in studying the use of stem cells to regenerate heart muscle in patients who have had heart attacks. In 2009, Marbán and his team completed the world's first procedure in which a patient's own heart tissue was used to grow specialized heart stem cells. The specialized cells were then injected back into the patient's heart in an effort to repair and regrow healthy muscle in a heart that had been injured by a heart attack. Results, published in The Lancet in 2012, showed that one year after receiving the experimental stem cell treatment, heart attack patients demonstrated a significant reduction in the size of the scar left on the heart muscle.

Earlier this year, Heart Institute researchers began a new study, called ALLSTAR, in which heart attack patients are being infused with allogeneic stem cells, which are derived from donor-quality hearts.

Recently, the Heart Institute opened the nation's first Regenerative Medicine Clinic, designed to match heart and vascular disease patients with appropriate stem cell clinical trials being conducted at Cedars-Sinai and other institutions.

"We are committed to thoroughly investigating whether stem cells could repair heart damage caused by Duchenne muscular dystrophy," Marbán said.

In the study, 78 lab mice were injected with cardiac stem cells. Over the next three months, the lab mice demonstrated improved pumping ability and exercise capacity in addition to a reduction in heart inflammation. The researchers also discovered that the stem cells work indirectly, by secreting tiny fat droplets called exosomes. The exosomes, when purified and administered alone, reproduce the key benefits of the cardiac stem cells.

Marbán said the procedure could be ready for testing in human clinical studies as soon as next year. The process to grow cardiac-derived stem cells was developed by Marbán when he was on the faculty of Johns Hopkins University. Johns Hopkins has filed for a patent on that intellectual property and has licensed it to Capricor, a company in which Cedars-Sinai and Marbán have a financial interest. Capricor is providing funds for the ALLSTAR clinical trial at Cedars-Sinai.

The Cedars-Sinai Heart Institute has been at the forefront of developing investigational stem cell treatments for heart attack patients.

A new approach to fighting chronic myeloid leukemia

Fuente: http://www.eurekalert.org/pub_releases/2014-11/epfd-ana111214.php

Chronic myeloid leukemia develops when a gene mutates and causes an enzyme to become hyperactive, causing blood-forming stem cells in the bone marrow to grow rapidly into abnormal cells. The enzyme, Abl-kinase, is a member of the "kinase" family of enzymes, which serve as an "on" or "off" switch for many functions in our cells. In chronic myeloid leukemia, the hyperactive Abl-kinase is targeted with drugs that bind to a specific part of the enzyme and block it, aiming to ultimately kill the fast-growing cancer cell. However, treatments are often limited by the fact that the cancer cells can adapt to resist drugs. EPFL scientists have identified an alternative part of Abl-kinase on which drugs can bind and act with a reduced risk of drug resistance. Their work is published in Nature Communications.

Abl-kinase can turn "on" molecules that are involved in many cell functions including cell growth. In chronic myeloid leukemia, the chromosome that contains the gene for Abl-kinase swaps a section with another chromosome, causing what is known as the "Philadelphia chromosome". When this mutation takes place in the blood stem cells in the bone marrow, Abl-kinase fuses with another protein, turning into a deregulated, hyperactive enzyme. This causes large numbers of blood-forming stem cells to grow into an abnormal type of white blood cell, which gives rise to chronic myeloid leukemia.

To treat this type of leukemia we use drugs that specifically bind and block a part of Abl-kinase called the "active site". As the name suggests, this is the part of the enzyme that binds molecules to turn them on. Therefore, blocking the active site with a drug stops the hyperactivity of Abl-kinase caused by the Philadelphia mutation and slow down or even abolishes the production of abnormal cancerous blood cells. The problem is that targeting the active site of Abl-kinase often causes the cancer cells to adapt and develop drug resistance, making them harder to kill.

A team of researchers led by Oliver Hantschel at EPFL (ISREC) has now discovered a new way to indirectly inhibit the activity of Abl-kinase. The scientists systematically made small, strategic mutations to Abl-kinase that caused its 3D structure to change. Then they tested each mutant version of the enzyme to see if its function would change.

Hantschel's team built on previous studies showing that Abl-kinase is indirectly controlled by another part of itself called the "SH2 region", which is located close to the active site. Normally, the SH2 region regulates the active site by opening and closing it. But under the Philadelphia mutation, that regulation is lost. What the scientists discovered was that when the Philadelphia mutation takes effect, the SH2 region actually "clamps" open the active site of Abl-kinase and forces it to go into overdrive.

The discovery provides a first-ever picture of the molecular events surrounding the hyperactivity of Abl-kinase. By blocking the SH2 region, it is possible to modulate the activity of the enzyme, and perhaps stop the growth of leukemic tumors. And since because the SH2 region is common to other kinases, it is likely that effect could extend to other types of cancers as well, particularly those characterized by abnormal kinase activity. Finally, Oliver Hantschel expects that this approach could overcome the problem of tumor drug resistance, as it might offer an alternative way to inhibit the enzyme and mutations of rapidly growing tumor cells may be less likely to occur.

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This work was supported by the ISREC Foundation and the Swiss Cancer League.

Reference

Lamontanara AJ, Georgeon S, Tria G, Svergun DI, Hantschel O. The SH2 domain of Abl kinases regulates kinase autophosphorylation by controlling activation loop accessibility. Nature Communications DOI: NCOMMS6470