Amniotic stem cells promote growth of functional blood vessels in healing hydrogels

Fuente: http://www.news-medical.net/news/20150410/Amniotic-stem-cells-promote-growth-of-functional-blood-vessels-in-healing-hydrogels.aspx

Rice University and Texas Children's Hospital scientists are using stem cells from amniotic fluid to promote the growth of robust, functional blood vessels in healing hydrogels.

In new experiments, the lab of bioengineer Jeffrey Jacot combined versatile amniotic stem cells with injectable hydrogels used as scaffolds in regenerative medicine and proved they enhance the development of vessels needed to bring blood to new tissue and carry waste products away.

The results appear in the Journal of Biomedical Materials Research Part A.

Jacot and his colleagues study the use of amniotic fluid cells from pregnant women to help heal infants born with congenital heart defects. Such fluids, drawn during standard tests, are generally discarded but show promise for implants made from a baby's own genetically matched material.

He contends amniotic stem cells are valuable for their ability to differentiate into many other types of cells, including endothelial cells that form blood vessels.

"The main thing we've figured out is how to get a vascularized device: laboratory-grown tissue that is made entirely from amniotic fluid cells," Jacot said. "We showed it's possible to use only cells derived from amniotic fluid."

In the lab, researchers from Rice, Texas Children's Hospital and Baylor College of Medicine combined amniotic fluid stem cells with a hydrogel made from polyethylene-glycol and fibrin. Fibrin is a biopolymer critical to blood clotting, cellular-matrix interactions, wound healing and angiogenesis, the process by which new vessels branch off from existing ones. Fibrin is widely used as a bioscaffold but suffers from low mechanical stiffness and rapid degradation. Combining fibrin and polyethylene-glycol made the hydrogel much more robust, Jacot said.

The lab used vascular endothelial growth factor to prompt stem cells to turn into endothelial cells, while the presence of fibrin encouraged the infiltration of native vasculature from neighboring tissue.

Mice injected with fibrin-only hydrogels showed the development of thin fibril structures, while those infused with the amniotic cell/fibrin hydrogel showed far more robust vasculature, according to the researchers.

Similar experiments using hydrogel seeded with bone marrow-derived mesenchymal cells also showed vascular growth, but without the guarantee of a tissue match, Jacot said. Seeding with endothelial cells didn't work as well as the researchers expected, he said.

The lab will continue to study the use of amniotic cells to build biocompatible patches for the hearts of infants born with birth defects and for other procedures, Jacot said.

Crean vasos sanguíneos de laboratorio que crecen en una semana

Fuente: http://www.tendencias21.net/Crean-vasos-sanguineos-de-laboratorio-que-crecen-en-una-semana_a38134.html

La tecnología para la creación de nuevos tejidos a partir de células madre ha dado un paso importante con un estudio llevado a cabo en Suecia. Científicos de ese país han conseguido desarrollar vasos sanguíneos nuevos en tan sólo siete días, a partir de células madre de una cantidad de sangre de los propios pacientes equivalente a dos cucharadas. Una vez trasplantados, los vasos han demostrado ser funcionales.

Los científicos obtuvieron las células madre para el desarrollo de vasos sanguíneos de pequeñas muestras de sangre. 

La tecnología para la creación de nuevos tejidos a partir de células madre ha dado un paso importante con un estudio llevado a cabo en la Sahlgrenska Academy y en el Hospital Universitario Sahlgrenska de Suecia. 

Científicos de ambos centros han conseguido desarrollar vasos sanguíneos nuevos en tan sólo siete días, a partir de una cantidad de sangre pequeña, equivalente a unas dos cucharadas. 

Hace sólo tres años, un paciente del Hospital Universitario Sahlgrenska ya recibió un trasplante de vasos sanguíneos desarrollados a partir de sus propias células madre. 

Hace dos años, otros dos pacientes, en este caso, dos niños pequeños que estaban perdiendo la vena que une el tracto gastrointestinal con el hígado, también recibieron una vena sustituta desarrollada a partir de sus propias células madre. 

En el primer caso, se obtuvieron las células madre de la médula ósea, un procedimiento que resulta muy doloroso. En el caso de los niños, en cambio, los doctores encontraron una manera de obtener células madre sin tener que recurrir a ese procedimiento. Lo hicieron a partir de una muestra de sangre de 25 mililitros (el equivalente aproximado a dos cucharadas).

Según publica la Universidad de Gotemburgo en un comunicado este procedimiento de extracción funcionó a la perfección a la primera. 

Además, “todo el proceso llevó sólo una semana, a diferencia de un mes en el primer caso. La sangre contiene sustancias que promueven el crecimiento natural", asegura Suchitra Sumitran-Holgersson, una de las autoras del avance. 

La investigadora y su colaborador, Michael Olausson, han tratado ya a tres pacientes con este sistema. Dos de ellos tienen venas que están funcionando como deberían. En el tercer caso, otro niño, éste se encuentra bajo vigilancia médica y el resultado es más incierto. 

Aún así, los científicos consideran que estos resultados son alentadores: “Creemos que este avance tecnológico y su difusión puede beneficiar a otros grupos de pacientes, como aquellos con venas varicosas o infarto de miocardio que necesitan nuevos vasos sanguíneos", asegura Holgersson. Y va más allá: "Nuestro sueño es ser capaz de hacer crecer órganos completos para superar la actual escasez de donantes", añade.

Referencia bibliográfica: 

Michael Olausson, Vijay Kumar Kuna, Galyna Travnikova, Henrik Bäckdahl, Pradeep B. Patil, Robert Saalman, Helena Borg, Anders Jeppsson, Suchitra Sumitran-Holgersson. In vivo application of tissue-engineered veins using autologous peripheral whole blood: A proof of concept study . EBioMedicine (2014). DOI: 10.1016/j.ebiom.2014.09.001.

Adult stem cells help build human blood vessels in engineered tissues

Fuente: http://www.sciencedaily.com/releases/2013/10/131014113739.htm?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+sciencedaily+%28ScienceDaily%3A+Latest+Science+News%29

Researchers at the University of Illinois at Chicago have identified a protein expressed by human bone marrow stem cells that guides and stimulates the formation of blood vessels.

Their findings, which could help improve the vascularization of engineered tissues, were reported online in the Journal of Molecular and Cellular Cardiology.

"Some stem cells actually have multiple jobs," says Dr. Jalees Rehman, associate professor of cardiology and pharmacology at the UIC College of Medicine and lead author of the paper. For example, stem cells in the bone marrow, he said, differentiate into bone or cartilage, but also have a secondary role in helping to support other cells in the bone marrow.

Rehman and his colleagues, who are developing engineered tissues for use in cardiac patients, observed that certain stem cells in bone marrow, called mesenchymal stem cells, seemed crucial for organizing other cells into functional blood vessels.

The researchers demonstrated that when they mixed mesenchymal stem cells from human bone marrow with the endothelial cells that line blood vessels, the stem cells elongated to form scaffolds and the endothelial cells organized around them to form tubes.

"But without the stem cells, the endothelial cells just sat there," said Rehman.

When the cell mixtures were implanted into mice, blood vessels formed that were able to support the flow of blood. To find out how the stem cells were helping promote blood vessel formation, the researchers looked at which genes were being expressed when the stem cells and endothelial cells were combined.

They tested two different stem cell lines from human bone marrow. One line supported the formation of blood vessel networks when it was mixed with endothelial cells, while the other cell line did not.

They analyzed the genetic signature and proteins of the respective cell lines and found that the vessel-supporting stem cell line released high levels of a blood vessel guidance molecule -- SLIT3. In the mixture that didn't form blood vessels, the SLIT3 gene was hardly expressed, Rehman said.

"This means that not all stem cells are created alike in terms of their SLIT3 production and their ability to encourage blood vessel formation," Rehman said. "While using a patient's own stem cells for making blood vessels is ideal because it eliminates the problem of immune rejection, it might be a good idea to test a patient's stem cells first to make sure they are good producers of SLIT3. If they aren't, the engineered vessels may not thrive, or even fail to grow."

Mesenchymal stem cell injections are currently being evaluated in clinical trials to see if they can help grow blood vessels and improve heart function in patients who have suffered heart attacks. So far, the benefits of stem cell injection have been modest, Rehman said. "Evaluating the gene and protein signatures of stem cells from each patient may allow for a more individualized approach, so that every patient receives mesenchymal stem cells that are most likely to promote blood vessel growth and cardiac repair. Hopefully, this will substantially increase the efficacy of stem cell treatments for heart patients." 

Co-authors on the research publication are Jonathan Paul and Vytas Bindokas of the University of Chicago Pritzker School of Medicine; Kareen Coulombe, David Smith and Charles Murry at the University of Washington, and Peter Toth, Yanmin Zhang and Glenn Marsboom of UIC.

This research was funded by grants from the National Institutes of Health (R01-GM094220, K08-HL080082, RO1-HL084642, P01-HL094374, P01-GM81619, U01-HL100405, T32-HL007381, T32-HL007312) and by the Heart Research Foundation.

Journal Reference:

Jonathan D. Paul, Kareen L.K. Coulombe, Peter T. Toth, Yanmin Zhang, Glenn Marsboom, Vytas P. Bindokas, David W. Smith, Charles E. Murry, Jalees Rehman. SLIT3–ROBO4 activation promotes vascular network formation in human engineered tissue and angiogenesis in vivo.Journal of Molecular and Cellular Cardiology, 2013; 64: 124 DOI: 10.1016/j.yjmcc.2013.09.005