Obtienen tejido funcional de intestino a partir de células humanas

Fuente: http://noticias.lainformacion.com/salud/especializaciones-medicas/investigadores-hacen-crecer-tejido-funcional-de-intestino-a-partir-de-celulas-humanas_qt6xGImb7sBlXS6BnwsbO1/

Un nuevo estudio realizado por investigadores del Hospital Infantil de Los Ángeles (CHLA, por sus siglas en inglés), en Estados Unidos, ha demostrado que el tejido de intestino delgado fabricado mediante ingeniería a partir de células humanas replica aspectos clave de un intestino humano funcional. El tejido de ingeniería de intestino delgado tiene importantes elementos del revestimiento de la mucosa y las estructuras de sustento, incluyendo la capacidad de absorber los azúcares y componentes incluso diminutos o ultraestructurales como conexiones celulares.

Publicado en la edición digital de 'American Journal of Physiology: GI & Liver', el trabajo permite a los cirujanos avanzar para ayudar más a los pacientes humanos usando esta técnica de medicina regenerativa. El tejido de intestino delgado fabricado mediante ingeniería (TESI, por sus siglas en ingés) crece a partir de células madre contenidas en el intestino y ofrece un tratamiento prometedor para el síndrome de intestino corto (SBS, por sus siglas en inglés), una causa importante de insuficiencia intestinal, especialmente en los bebés prematuros y recién nacidos con anomalías intestinales congénitas.

TESI puede algún día ofrecer una alternativa terapéutica al tratamiento estándar actual, que es el trasplante de intestino, y podría potencialmente resolver sus desafíos más grandes, la escasez de donantes y la necesidad de inmunosupresión de por vida. Tracy C. Grikscheit, investigador principal en el Instituto Saban de Investigación de CHLA y de su Programa de Biología del Desarrollo y Medicina Regenerativa, es también cirujano pediátrico en el Hospital Infantil de Los Ángeles y profesor asistente de Cirugía en la Escuela de Medicina Keck de la Universidad del Sur de California.

Grikscheit tiene como objetivo ayudar a sus pacientes jóvenes más vulnerables, incluidos los bebés que nacen prematuramente y desarrollan una enfermedad devastadora llamada enterocolitis necrotizante (ECN), que pone en peligro su vida al dañar el intestino y que requiere la eliminación de grandes porciones del intestino delgado. Sin suficiente longitud intestinal, los bebés dependen de la alimentación intravenosa, lo que es costoso y puede causar daño al hígado. ENC y otros trastornos de insuficiencia intestinal ocurren en 24,5 de cada 100.000 nacidos vivos y la incidencia de la SBS está aumentando, con casi un tercio de los pacientes que mueren dentro de los cinco años.

Científicos de CHLA habían demostrado previamente que TESI podría generarse implantando tejido de intestino delgado de donantes implantado en ratones inmunodeprimidos. Sin embargo, en estos estudios iniciales, publicados en julio de 2011 en la revista biomédica 'Tissue Engineering, Part A', sólo se identificaron los componentes básicos del intestino. Para que tuvieran relevancia clínica, se vio necesario investigar más a fondo componentes como la capacidad de formar una barrera saludable mientras se absorben los nutrientes o mecanismos específicos de intercambio de electrolitos.

El nuevo estudio determinó que el ratón TESI es muy similar al TESI derivado de células humanas y que ambos contienen elementos importantes tales como las células madre y progenitoras que continuarán regenerando el intestino igual que el reemplazo del tejido vivo. Y estas células se encuentran dentro de la ingeniería tisular en lugares específicos y en estrecha proximidad a otras células especializadas que se sabe que son necesarias en el intestino humano sano para un órgano en pleno funcionamiento.

"Hemos demostrado que podemos hacer crecer tejido de ingeniería de intestino delgado que es más complejo que otros modelos de células madre o células progenitoras que se utilizan actualmente para estudiar la regeneración intestinal y la enfermedad, y probado que es totalmente funcional ya que se desarrolla a partir de células humanas", destaca Grikscheit. "Es un hito necesario en nuestro camino para ayudar a pacientes con insuficiencia intestinal", concluye.

Researchers grow functional tissue-engineered intestine from human cells

Fuente: http://medicalxpress.com/news/2015-01-functional-tissue-engineered-intestine-human-cells.html

Tracy C. Grikscheit of The Saban Research Institute of Children's Hospital Los Angeles. 

A new study by researchers at Children's Hospital Los Angeles has shown that tissue-engineered small intestine grown from human cells replicates key aspects of a functioning human intestine. The tissue-engineered small intestine they developed contains important elements of the mucosal lining and support structures, including the ability to absorb sugars, and even tiny or ultra-structural components like cellular connections.

Published by the American Journal of Physiology: GI & Liver, the work brings surgeons one step closer to helping human patients using this regenerative medicine technique.

Tissue-engineered small intestine (TESI) grows from stem cells contained in the intestine and offers a promising treatment for short bowel syndrome (SBS), a major cause of intestinal failure, particularly in premature babies and newborns with congenital intestinal anomalies. TESI may one day offer a therapeutic alternative to the current standard treatment, which is intestinal transplantation, and could potentially solve its largest challenges - donor shortage and the need for lifelong immunosuppression.

Tracy C. Grikscheit, MD, a principal investigator in The Saban Research Institute of CHLA and its Developmental Biology and Regenerative Medicine program, is also a pediatric surgeon at Children's Hospital Los Angeles and an assistant professor of surgery at the Keck School of Medicine of the University of Southern California.

Grikscheit aims to help her most vulnerable young patients, including babies who are born prematurely and develop a devastating disease called necrotizing enterocolitis (NEC), where life-threatening intestinal damage requires removal of large portions of the small intestine. Without enough intestinal length, the babies are dependent on intravenous feeding, which is costly and may cause liver damage. NEC and other contributors to intestinal failure occur in 24.5 out of 100,000 live births, and the incidence of SBS is increasing. Nearly a third of patients die within five years.

CHLA scientists had previously shown that TESI could be generated from human small intestine donor tissue implanted into immunocompromised mice. However, in those initial studies - published in July 2011 in the biomedical journal Tissue Engineering, Part A - only basic components of the intestine were identified. For clinical relevance, it remained necessary to more fully investigate intact components of function such as the ability to form a healthy barrier while still absorbing nutrition or specific mechanisms of electrolyte exchange.

The new study determined that mouse TESI is highly similar to the TESI derived from human cells, and that both contain important building blocks such as the stem and progenitor cells that will continue to regenerate the intestine as a living tissue replacement. And these cells are found within the engineered tissue in specific locations and in close proximity to other specialized cells that are known to be necessary in healthy human intestine for a fully functioning organ.

"We have shown that we can grow tissue-engineered small intestine that is more complex than other stem cell or progenitor cell models that are currently used to study intestinal regeneration and disease, and proven it to be fully functional as it develops from human cells," said Grikscheit. "Demonstrating the functional capacity of this tissue-engineered intestine is a necessary milestone on our path toward one day helping patients with intestinal failure."

Amniotic fluid stem cells repair gut damage

Fuente: http://www.eurekalert.org/pub_releases/2013-03/ucl-afs032213.php

Stem cells taken from amniotic fluid were used to restore gut structure and function following intestinal damage in rodents, in new research published in the journal Gut. The findings pave the way for a new form of cell therapy to reverse serious damage from inflammation in the intestines of babies.

The study, funded by Great Ormond Street Hospital Children's Charity, investigated a new way to treat necrotizing enterocolitis (NEC), where severe inflammation destroys tissues in the gut. NEC is the most common gastrointestinal surgical emergency in newborn babies, with mortality rates of around 15 to 30 per cent in the UK.

While breast milk and probiotics can help to reduce the incidence of the disease, no medical treatments are currently available other than surgery once NEC sets in. Surgical removal of the dead tissue shortens the bowel and can lead to intestinal failure, with some babies eventually needing ongoing parenteral nutrition (feeding via an intravenous line) or an intestinal transplant.

In the study, led by the UCL Institute of Child Health, amniotic fluid stem (AFS) cells were harvested from rodent amniotic fluid and given to rats with NEC. Other rats with the same condition were given bone marrow stem cells taken from their femurs, or fed as normal with no treatment, to compare the clinical outcomes of different treatments.

NEC-affected rats injected with AFS cells showed significantly higher survival rates a week after being treated, compared to the other two groups. Inspection of their intestines, including with micro magnetic resonance imaging (MRI), showed the inflammation to be significantly reduced, with fewer dead cells, greater self-renewal of the gut tissue and better overall intestinal function.

While bone marrow stem cells have been known to help reverse colonic damage in irritable bowel disease by regenerating tissue, the beneficial effects from stem cell therapy in NEC appear to work via a different mechanism. Following their injection into the gut, the AFS cells moved into the intestinal villi - the small, finger-like projections that protrude from the lining of the intestinal wall and pass nutrients from the intestine into the blood. However, rather than directly repairing the damaged tissue, the AFS cells appear to have released specific growth factors that acted on progenitor cells in the gut which in turn, reduced the inflammation and triggered the formation of new villi and other tissues.

Dr Paolo De Coppi, UCL Institute of Child Health, who led the study, says: "Stem cells are well known to have anti-inflammatory effects, but this is the first time we have shown that amniotic fluid stem cells can repair damage in the intestines. In the future, we hope that stem cells found in amniotic fluid will be used more widely in therapies and in research, particularly for the treatment of congenital malformations. Although amniotic fluid stem cells have a more limited capacity to develop into different cell types than those from the embryo, they nevertheless show promise for many parts of the body including the liver, muscle and nervous system."

Dr Simon Eaton, UCL Institute of Child Health and co-author of the study, adds: "Once we have a better understanding of the mechanisms by which AFS cells trigger repair and restore function in the gut, we can start to explore new cellular or pharmacological therapies for infants with necrotizing enterocolitis."

###

Notes to editors

For further information, please contact Jenny Gimpel at the GOSH-ICH press office on + 44 (0)20 7239 3043 or jenny.gimpel@gosh.org.

'Amniotic fluid stem cells improve survival and enhance repair of damaged intestine in NEC via a COX-2 dependent mechanism' by Zani et al, is published on Monday 25 March 2013 in the journal Gut. To obtain a copy of the paper, please contact Jenny Gimpel at the GOSH-ICH press office.

The study was funded by Great Ormond Street Hospital Children's Charity, with support from the Fondazione Citta della Speranza.

Contact: Jenny Gimpel

jenny.gimpel@gosh.org

44-020-723-93043

University College London

Amniotic fluid stem cells repair gut damage

Fuente: http://www.sciencedaily.com/releases/2013/03/130324202036.htm?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+sciencedaily+%28ScienceDaily%3A+Latest+Science+News%29

Stem cells taken from amniotic fluid were used to restore gut structure and function following intestinal damage in rodents, in new research published in the journal Gut. The findings pave the way for a new form of cell therapy to reverse serious damage from inflammation in the intestines of babies.

The study, funded by Great Ormond Street Hospital Children's Charity, investigated a new way to treat necrotizing enterocolitis (NEC), where severe inflammation destroys tissues in the gut. NEC is the most common gastrointestinal surgical emergency in newborn babies, with mortality rates of around 15 to 30 per cent in the UK.

While breast milk and probiotics can help to reduce the incidence of the disease, no medical treatments are currently available other than surgery once NEC sets in. Surgical removal of the dead tissue shortens the bowel and can lead to intestinal failure, with some babies eventually needing ongoing parenteral nutrition (feeding via an intravenous line) or an intestinal transplant.

In the study, led by the UCL Institute of Child Health, amniotic fluid stem (AFS) cells were harvested from rodent amniotic fluid and given to rats with NEC. Other rats with the same condition were given bone marrow stem cells taken from their femurs, or fed as normal with no treatment, to compare the clinical outcomes of different treatments.

NEC-affected rats injected with AFS cells showed significantly higher survival rates a week after being treated, compared to the other two groups. Inspection of their intestines, including with micro magnetic resonance imaging (MRI), showed the inflammation to be significantly reduced, with fewer dead cells, greater self-renewal of the gut tissue and better overall intestinal function.

While bone marrow stem cells have been known to help reverse colonic damage in irritable bowel disease by regenerating tissue, the beneficial effects from stem cell therapy in NEC appear to work via a different mechanism. Following their injection into the gut, the AFS cells moved into the intestinal villi -- the small, finger-like projections that protrude from the lining of the intestinal wall and pass nutrients from the intestine into the blood. However, rather than directly repairing the damaged tissue, the AFS cells appear to have released specific growth factors that acted on progenitor cells in the gut which in turn, reduced the inflammation and triggered the formation of new villi and other tissues.

Dr Paolo De Coppi, UCL Institute of Child Health, who led the study, says: "Stem cells are well known to have anti-inflammatory effects, but this is the first time we have shown that amniotic fluid stem cells can repair damage in the intestines. In the future, we hope that stem cells found in amniotic fluid will be used more widely in therapies and in research, particularly for the treatment of congenital malformations. Although amniotic fluid stem cells have a more limited capacity to develop into different cell types than those from the embryo, they nevertheless show promise for many parts of the body including the liver, muscle and nervous system."

Dr Simon Eaton, UCL Institute of Child Health and co-author of the study, adds: "Once we have a better understanding of the mechanisms by which AFS cells trigger repair and restore function in the gut, we can start to explore new cellular or pharmacological therapies for infants with necrotizing enterocolitis."

Células madre del líquido amniótico pueden tratar la enterocolitis necrotizante, enfermedad común en los bebés prematuros

Fuentes: http://www.abc.es/salud/noticias/celulas-liquido-aminiotico-para-tratar-14523.html
http://www.onmeda.es/noticias_salud/noticias/c%C3%A9lulas_madre_del_l%C3%ADquido_amni%C3%B3tico_pueden_tratar_la_enterocolitis_necrotizante-999.html
http://www.bbc.co.uk/mundo/ultimas_noticias/2013/03/130325_ultnot_bebes_liquido_amniotico_men.shtml

El líquido amniótico, que rodea y protege al embrión en desarrollo en el útero, podría tener la clave para curar una grave enfermedad intestinal que afecta a los bebés prematuros. El trastorno, una inflamación severa llamada enterocolitis necrotizante, puede destruir los tejidos del intestino y conducir a fallo orgánico múltiple y muerte.

Un estudio realizado con animales, publicado en la revista Gut, una pulicación internacional de Gastroenterología y Hepatología, muestra que las células madre del líquido amniótico pueden reparar parte del daño e incrementar las posibilidades de supervivencia.

La enterocolitis necrotizante es una de las causas más importantes de morbilidad y de mortalidad en neonatos. Por ese motivo, un equipo del Instituto de Salud Infantil del University College de Londres decidió aplicar a esta patología un nuevo enfoque, utilizando células madre, una opción terapéutica que ya se emplea en otras enfermedades intestinales.

Algunos órganos de los bebés prematuros no están preparados: aproximadamente uno de cada 10 bebés prematuros que están en cuidado intensivo neonatal desarrollan enterocolitis necrotizante. Aunque la leche materna puede reducir los riesgos, el único tratamiento principal es la cirugía para extirpar el tejido enfermo. Sin embargo, el 40% de los que necesitan cirugía no va a sobrevivir. «Es un problema importante que además va en aumento», explica Simon Eaton, del Instituto de Salud Infantil del University College de Londres.

La investigación, realizada en un modelo de rata capaz de desarrollar enterocolitis necrotizante mortal, mostró que el uso de inyecciones de células madre parece aumentar el tiempo de supervivencia. Eaton, en declaraciones a la BBC, aseguró que se había podido prolongar la supervivencia.

Para realizar la investigación, inyectaron células madre del líquido amniótico en el intestino de ratones enfermos de enterocolitis necrotizante, y analizaron su supervivencia, comportamiento y la inflamación de su intestino, entre otros parámetros.

Como resultado, observaron que, tras el tratamiento, la tasa de supervivencia de los animales había mejorado, así como sus condiciones clínicas. También había descendido la incidencia de la enterocolitis necrotizante y el daño intestinal, además de haber descendido la inflamación y mejorado la función intestinal.

Los autores concluyen que es importante entender completamente este mecanismo, de forma que pueda contribuir al desarrollo de nuevas terapias celulares o farmacológicas para bebés con enterocolitis necrotizante.

Se sabe que las células madre poseen efectos antiinflamatorios, pero esta es la primera vez que se ha demostrado que las células madre del liquido amniótico pueden reparar el daño intestinal. Ahora bien, los investigadores reconocen que harán falta muchas pruebas para averiguar si el tratamiento podría funcionar en los bebés.

Además, las células madre tendrían que ser de un donante, ya que no sería práctico para almacenar el líquido de cada parto. Ello significa que existe el riesgo de rechazo y de formación de tumores.

Referencia bibliográfica:

http://gut.bmj.com/content/early/2013/03/23/gutjnl-2012-303735.short?g=w_gut_ahead_tab