Adult stem cells selectively delivered into the eye and used to control angiogenesis at TSRI

July 29, 2002

A team of researchers from The Scripps Research Institute (TSRI) has discovered a way to use adult bone marrow stem cells to form new blood vessels in the eye or to deliver chemicals that will prevent the abnormal formation of new vessels.

This technique, which involves injecting the stem cells into the eye, could potentially be used to stimulate vessel growth and address inherited degenerations of the retina in the first instance, and in the second, to treat ocular diseases resulting from abnormal retinal angiogenesis, the aberrant growth of new blood vessels in the eye, which is the leading cause of vision loss in the United States.

"This is very exciting," says Martin Friedlander, M.D., Ph.D., who led the study. "We have shown that the cells can incorporate into the [degenerating] vasculature and make it normal."

"And when loaded with antiangiogenics, they can selectively wipe out the formation of new blood vessels."

Friedlander, who is Associate Professor in the Department of Cell Biology and Chief of the Retina Service in the Division of Ophthalmology, Department of Surgery at Scripps Clinic, has had a longstanding research program looking at ways of treating eye diseases that result from abnormal angiogenesis.

Abnormal angiogenesis is the cause of visual loss in age-related macular degeneration, where new blood vessels grow under the retina, and diabetic retinopathy, where abnormal vessels grow on top of the retina. The end result is much the same in these diseases--the normal structures for the transmission of light to the back of the eye are lost, and vision is catastrophically impeded in many of the tens of millions of Americans who suffer from them.

From stem cells to vessels

Adult bone marrow stem cells are "pluripotent" which means they have the potential to develop into a number of different cell types, such as red blood cells, platelets, or lymphocytes. The group's basic technique starts with selecting stem cells from the bone marrow that have the capability of becoming endothelial cells, the major cell type lining blood vessels.

Normally, retinal vascular formation occurs late in human prenatal development, when endothelial cells form a fine mesh of blood vessels in the back of the eye. In diseases like macular degeneration and diabetic retinopathy, aberrant vascular formation occurs later in life.

The vascularization in both diseases involves endothelial cells working in concert with another specialized cell--star-shaped cells called "astrocytes." These astrocytes, when activated, act as a template for vessel formation.

During prenatal human development, activated astrocytes guide endothelial cells into place where they can proliferate and form blood vessels. And later in life, activated astrocytes can also act as a template for endothelial cells to form blood vessels during angiogenesis.

Friedlander and his team found that they were able to target the activated astrocytes with the stem cell in vivo. They then tested these stem cells in a mouse model system of ocular disease. In normal mice, retinal blood vesssels form during the first three weeks after birth. In the disease model, the deeper retinal vessels completely degenerate by one month after birth.

In the ocular disease models, the stem cells differentiated into endothelial cells and proliferated, forming new blood vessels. This actually rescued and stabilized the retinal vessels when they would otherwise be degenerated.

They also found that they could shut down the angiogenesis by first transfecting the stem cells with a powerful inhibitor of angiogenesis--a fragment of the human protein tryptophanyl-tRNA synthetase (T2-TrpRS), which was discovered by TSRI Professor Paul Schimmel, Ph.D., and Friedlander and described in an article by the two investigators last year.

These transfected stem cells were also guided by the retinal astrocytes to the vasculature in the back of the eye where they expressed the T2-TrpRS protein and prevented the development of new retinal blood vessels without affecting already established blood vessels.

The research article "Bone marrow-derived stem cells target retinal astrocytes and can promote or inhibit retinal angiogenesis" is authored by Atushi Otani, Karen Kinder, Karla L. Ewalt, Francella J. Otero, Paul Schimmel, and Martin Friedlander and appears in the September, 2002 issue of Nature Medicine, appearing online as part of the advance online publication section of the journal's web site on July 29, 2002. See http://www.nature.com/nm/.
-end-
The research was primarily funded by the National Eye Institute with additional support from The National Cancer Institute, The Skaggs Institute for Chemical Biology, The Robert Mealey Program for the Study of Macular Degenerations, Merck KgaA, and the National Foundation for Cancer Research.

Scripps Research Institute

Related Stem Cells Articles from Brightsurf:

SUTD researchers create heart cells from stem cells using 3D printing
SUTD researchers 3D printed a micro-scaled physical device to demonstrate a new level of control in the directed differentiation of stem cells, enhancing the production of cardiomyocytes.

More selective elimination of leukemia stem cells and blood stem cells
Hematopoietic stem cells from a healthy donor can help patients suffering from acute leukemia.

Computer simulations visualize how DNA is recognized to convert cells into stem cells
Researchers of the Hubrecht Institute (KNAW - The Netherlands) and the Max Planck Institute in Münster (Germany) have revealed how an essential protein helps to activate genomic DNA during the conversion of regular adult human cells into stem cells.

First events in stem cells becoming specialized cells needed for organ development
Cell biologists at the University of Toronto shed light on the very first step stem cells go through to turn into the specialized cells that make up organs.

Surprising research result: All immature cells can develop into stem cells
New sensational study conducted at the University of Copenhagen disproves traditional knowledge of stem cell development.

The development of brain stem cells into new nerve cells and why this can lead to cancer
Stem cells are true Jacks-of-all-trades of our bodies, as they can turn into the many different cell types of all organs.

Healthy blood stem cells have as many DNA mutations as leukemic cells
Researchers from the Princess Máxima Center for Pediatric Oncology have shown that the number of mutations in healthy and leukemic blood stem cells does not differ.

New method grows brain cells from stem cells quickly and efficiently
Researchers at Lund University in Sweden have developed a faster method to generate functional brain cells, called astrocytes, from embryonic stem cells.

NUS researchers confine mature cells to turn them into stem cells
Recent research led by Professor G.V. Shivashankar of the Mechanobiology Institute at the National University of Singapore and the FIRC Institute of Molecular Oncology in Italy, has revealed that mature cells can be reprogrammed into re-deployable stem cells without direct genetic modification -- by confining them to a defined geometric space for an extended period of time.

Researchers develop a new method for turning skin cells into pluripotent stem cells
Researchers at the University of Helsinki, Finland, and Karolinska Institutet, Sweden, have for the first time succeeded in converting human skin cells into pluripotent stem cells by activating the cell's own genes.

Read More: Stem Cells News and Stem Cells Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.