Features | Partner Sites | Information | LinkXpress
Sign In

Treating Vascular Diseases with Reprogrammed Amniotic Fluid Cells

By BiotechDaily International staff writers
Posted on 01 Nov 2012
Scientists have devised a way to utilize diagnostic prenatal amniocentesis cells, reprogramming them into plentiful and stable endothelial cells capable of regenerating damaged blood vessels and repairing injured organs.

The study, published online October 2012 in the journal Cell, illustrates future therapy where amniotic fluid gathered from thousands of amniocentesis procedures annually, during mid-pregnancy to study fetal chromosomes, would be gathered with permission from the women tested. These cells, which are not embryonic, would then be treated with three genes that reprogram them rapidly into billions of endothelial cells. The new endothelial cells could then be frozen and banked similar to same way blood is, and patients who require blood vessel repair would be able to receive the cells with only one injection.

If the technology is validated in future studies, it could dramatically improve treatment for disorders associated an injured vascular system, including lung diseases such as emphysema, diabetes, and trauma, and heart disease, stroke, according to the study’s senior investigator, Dr. Shahin Rafii, a professor of genetic medicine at Weill Cornell Medical College (New York, NY, USA) and codirector of its Ansary Stem Cell Institute. “Currently, there is no curative treatment available for patients with vascular diseases, and the common denominator to all these disorders is dysfunction of blood vessels, specifically endothelial cells that are the building blocks of the vessels,” said Dr. Rafii.

But these cells do much more than just provide the accouterments to direct blood. Dr. Rafii has recently shown that endothelial cells in blood vessels generate growth factors that actively participate in organ maintenance, repair, and regeneration. Therefore, whereas damaged vessels cannot repair the organs they nurture with blood, he says an infusion of new endothelial cells could.

“Replacement of the dysfunctional endothelial cells with transplantation of normal, properly engineered cultured endothelial cells could potentially provide for a novel therapy for many patients,” said study coauthor Dr. Sina Rabbany, adjunct associate professor of bioengineering in genetic medicine at Weill Cornell. “In order to engineer tissues with clinically relevant dimensions, endothelial cells can be assembled into porous three-dimensional scaffolds that, once introduced into a patient’s injured organ, could form true blood vessels.”

According to Dr. Rafii, this study will potentially create a new field of translational vascular medicine. He predicted that only as much as four years are required for the preclinical research to seek US Food and Drug Administration (FDA) approval to begin human clinical trials to further the possibility of reprogrammed endothelial cells for treatment of vascular disorders.

The scientists confirmed, in mice models, that endothelial cells reprogrammed from human amniotic cells could engraft into an injured liver to form healthy, stable, and functional blood vessels. “We have shown that these engrafted endothelial cells have the capacity to produce unique growth factors to promote regeneration of the liver cells,” stated the study’s lead investigator, Dr. Michael Ginsberg, a senior postdoctoral associate in Dr. Rafii’s laboratory.

“The novelty of this technique is that, from 100,000 amniotic cells--a small amount--we grew more than six billion new authentic endothelial cells within a matter of weeks,” Dr. Ginsberg remarked. “And when we injected these cells into mice, a substantial amount of them engrafted into regenerating vessels. It was remarkable to see that these cells went right to work building new blood vessels in the liver as well as producing the right growth factors that could potentially regenerate and repair injured organs.”

In their first research with these cells three years ago, Dr. Ginsberg used cells taken from an amniocentesis given at 16 weeks of gestation. Researchers found that amniotic cells are the “Goldilocks” of cellular programming. “They are not as plastic and unstable as endothelial cells derived from embryonic cells or as stubborn as those produced from reprogramming differentiated adult cells,” Dr. Ginsberg said. Instead, he says amniotic cells provide conditions that are just right--so-called “Goldilocks principle”--for generating endothelial cells.

However, to make that finding, the researchers had to know how to reprogram the amniotic cells. To this end, they looked for the genes that embryonic stem cells use to differentiate into endothelial cells. Dr. Rafii’s group identified three genes that are expressed during vascular development, all of which are members of the E-twenty six (ETS) family of transcription factors known to regulate cellular differentiation, especially blood vessel formation.

Then, the scientists used gene transfer technology to insert the three genes into mature amniotic cells and shut one of them off after a short and vital period of activity by using a special molecular inhibitor. Remarkably, 20% of the amniotic cells could efficiently be reprogrammed into endothelial cells. “This is quite an achievement since current strategies to reprogram adult cells result less than 1% of the time in successful reprogramming into endothelial cells,” said Dr. Rafii.

“These transcription factors do not cause cancer, and the endothelial cells reprogrammed from human amniotic cells are not tumorigenic and could in the future be infused into patients with a large margin of safety,” said Dr. Ginsberg.

The findings suggest that other transcription factors could be used to reprogram the amniotic cells into many other tissue-specific cells, such as those that comprise pancreatic islet cells, muscles, the brain, and other areas of the body. “While our work focused primarily on the reprogramming of amniotic cells into endothelial cells, we surmise that through the use of other transcription factors and growth conditions, our group and others will be able to reprogram mouse and human amniotic cells virtually into every organ cell type, such as hepatocytes in the liver, cardiomyocytes in heart muscle, neurons in the brain and even chondrocytes in cartilage, just to name a few,” Dr. Ginsberg noted.

“Obviously, the implications of these findings would be enormous in the field of translational regenerative medicine,” emphasized study coauthor Dr. Zev Rosenwaks, a professor of reproductive medicine in obstetrics and gynecology at Weill Cornell Medical College and director and physician-in-chief of the Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine at New York-Presbyterian Hospital/Weill Cornell Medical Center. “The greatest obstacle to overcome in the pursuit to regenerate specific tissues and organs is the requirement for substantial levels of cells--in the billions--that are stable, safe, and durable. Our approach will bring us closer to this milestone.”

“Most importantly, these endothelial cells could be reprogrammed from amniotic cells from genetically diverse individuals,” stated co-author Dr. Venkat R. Pulijaal, director of the cytogenetic laboratory, associate professor of clinical pathology and laboratory medicine at Weill Cornell. What endothelial cells a patient receives would depend on their human leukocyte antigen (HLA) type, which is a set of self-recognition molecules that enable doctors to partner a patient with potential donors of blood or tissue.

A patent has been filed on the discovery.

Related Links:

Weill Cornell Medical College

comments powered by Disqus



view channel
Image: This novel, flexible film that can react to light is a promising step toward an artificial retina (Photo courtesy of the American Chemical Society).

Novel Nanofilm May Be Artificial Retina Precursor

Researchers have used advanced nanotechnology techniques to develop a light-sensitive film that has potential for future artificial retina applications. Investigators at the Hebrew University of Jerusalem... Read more

Drug Discovery

view channel
Image: Disruption and removal of malaria parasites by the experimental drug (+)-SJ733 (Photo courtesy of the University of California, San Francisco).

Experimental Antimalaria Drug Induces the Immune System to Destroy Infected Red Blood Cells

An experimental drug for the treatment of malaria was found to induce morphological changes in infected erythrocytes that enabled the immune system to recognize and eliminate them. Investigators at... Read more


view channel

Blocking Enzyme Switch Turns Off Tumor Growth in T-Cell Acute Lymphoblastic Leukemia

Researchers recently reported that blocking the action of an enzyme “switch” needed to activate tumor growth is emerging as a practical strategy for treating T-cell acute lymphoblastic leukemia. An estimated 25% of the 500 US adolescents and young adults diagnosed yearly with this aggressive disease fail to respond to... Read more


view channel

R&D Partnership Initiated to Reduce Development Time for New Drugs

nanoPET Pharma, GmbH (Berlin, Germany) signed an open-ended framework contract with the international pharmaceutical company Boehringer Ingelheim (Ridgefield, CT, USA). By developing customized contrast agents for research in both basic and preclinical studies, nanoPET Pharma will contribute to the enhancement of Boehringer... Read more
Copyright © 2000-2014 Globetech Media. All rights reserved.