In what has been described as a breakthrough, US scientists have found a new way to use human embryonic stem cells to produce precursor cells that can repair severely damaged blood vessels in mice and other laboratory animals. They hope this method will one day be used to repair extensive blood vessel damage in humans, for instance diabetics with damaged retinas, people with severe blood vessel damage in limbs (and thereby avoid amputation), and reducing deaths from heart attacks.
The research is published in the journal Nature Methods and is available as an early online issue.
In the study, scientists from Advanced Cell Technology (ACT) of Massachusetts, a stem cell company in the field of regenerative medicine, together with scientists from the University of Florida, Gainesville, Florida, and the Memorial Sloan-Kettering Cancer Center (MSKCC), New York, describe how they used human embryonic stem (hES) cells to generate large numbers of “bipotential pogenitor cells”, also called hemangioblasts, that differentiate into a range of cells, including blood cells, capillary wall cells and immune cells.
The scientists also describe how the cells were then able to generate working blood vessels in cases of both chronic disease and severe tissue injury.
When they injected the hemangionblast cells into animals with damaged retinas, the cells “homed” to the injured sites and started repairing the damaged vessels and within 24 to 48 hours the “entire damaged vascular structure” was showing signs of restored function.
The cells also showed a similar ability to regenerate and repair damaged vessels in animals following heart attacks. This resulted in a 50 per cent reduced death rate.
And in animals with “hind leg ischemia”, where major limb blood vessels were so damaged that amputation would normally be the only option, vascular repair was so effective that near normal levels of blood flow were restored.
Senior author of the study and Vice President of Research and Scientific Development at ACT, Dr Robert Lanza said that being able to repair vascular damage in this way could have a “profound impact on a large number of diseases that are major human afflictions”.
“Our results suggest the possibility of using nature’s early cellular developmental components to restore vascularization and function in patients with vascular disease. An injection of these cells may be able to prevent a patient from having a leg amputated or from dying after a heart attack,” he explained.
A significant feature of the method is that the scientists found a way to develop and differentiate human hemangioblasts into different cell lineages without using a serum culture derived from animal blood. Animal blood-based cultures invariably introduce unwanted viruses.
Other scientists have found hemangioblasts but not in enough numbers to do the kind of work described in the study.
Director of Differentiation at ACT and first author of the paper, Dr Shi-Jiang Lu, said they had developed, “for the first time a simple and highly scalable source of human hemangioblasts”.
” The elimination of serum and other animal components from the system, as well as the ability to generate an unlimited supply of these cells, will be important for future preclinical and human studies.”
Speaking about the potential applications for human treatments, for instance in diabetic patients with extensive blood vessel damage, such as in the retina, another research colloborator, Dr Maria Grant, Professor of Pharmacology at the University of Florida, said:
“These cells have a robust vascular reparative ability under what is typically considered very adverse growth conditions making them potentially ideal for treatment of diabetic vascular complications where profound tissue compromise exists and healing is typically severely compromised.”
So far, the method has only been demonstrated in animals, and the ACT study needs to be replicated by other scientists to prove the results are robust. Also, it needs to be confirmed by independent studies that the cells the ACT has found are indeed hemangioblasts.
But ACT is confident that “This breakthrough has the potential to benefit many Americans suffering from vascular disease”, an opinion voiced by its Chairman and CEO, William M. Caldwell, IV.
He said the company plans to file an Investigational New Drug Application with the US Food and Drug Administration (FDA) by the end of next year to test the clinical application of the cells in humans.
Research using embryonic, as opposed to adult stem cells is controversial because it currently relies on the destruction of human embryos.
“Generation of functional hemangioblasts from human embryonic stem cells.”
Shi-Jiang Lu, Qiang Feng, Sergio Caballero, Yu Chen, Malcolm A S Moore, Maria B Grant and Robert Lanza.
Nature Methods Published online: 7 May 2007
doi:10.1038/nmeth1041
Click here for more information on stem cells from the National Institutes of Health (US).
Written by: Catharine Paddock
Writer: Medical News Today