In a recent research article from the Johns Hopkins Institute of Cell Engineering, lead researcher Elias T. Zambidis and colleagues show that a well-known enzyme in the body is a novel way to identify the stem cells that form the blood and circulatory system, which will open new roads to tissue engineering for regenerative medicine.
The Zambidis research team is primarily interested in creating a cell, called a hemangioblast, which is a precursor to all the cells of the blood system, like red and white blood cells, as well as to other cells in the circulatory system, including the endothelial cells that make up arteries and veins.
The researchers achieved this by deriving hemangioblasts from embryonic stem cells (ESCs). ESCs are known as pluripotent stem cells and are able to give rise to any type of cell in the body under the correct conditions, including cells in the blood system, nervous tissue and muscle tissue. It is this remarkable ability of ESCs that holds such promise for the area of regenerative medicine.
Understanding and having the ability to create any type of tissue in the body holds great promise for curing many conditions such as autoimmune diseases, muscular dystrophies and degenerative diseases like Alzheimer's and diabetes.
During mammalian development, the egg is fertilized by the sperm and proceeds through an intricate and complex process that eventually leads to the adult organism. In the early stages of development, especially in the first few weeks, the interplay between cellular pathways determines the cell-types that emerge, such as those of the blood system. Understanding these pathways is difficult enough, but to recreate them in a test tube is perhaps even more daunting.
This is what Zambidis and his team have taken a step towards. They have created hemangioblast cells in a test tube, or in vitro, and found a novel use for a well-known enzyme in the body which allows them to identify the creation of the hemangioblast.
The enzyme is called angiotensin-converting enzyme (ACE) and is involved in such processes in the body as regulating blood pressure, the formation of new blood vessels, and also inflammation. ACE inhibitors, a class of medicines commonly taken by people with high blood pressure and heart disease, act on this enzyme.
The scientists were able to recognize these cells by using antibodies that specifically target cells expressing ACE on their surface. They can then isolate these cells using machines that rapidly sort cells based on cell-surface markers.
First, the team cultured ESCs in vitro and then gave these cells specific growth factors, which turn the ESCs into the hemangioblast cell. The researchers looked at the cells periodically and isolated the cells that expressed ACE on their surface; these cells would then continue to be cultured until they obtained a population of hemangioblasts.
Once this was done, the next step was to learn how to turn the hemangioblast into the cells further down its lineage, such as blood cells and endothelial cells. One important finding is that ACE actually helps in the process of turning the hemangioblast into other cells. By treating the cells with an ACE inhibitor, scientists could make the cells become endothelial cells but not blood cells.
These findings will create new possibilities in the field of regenerative medicine. They could offer the ability to create millions of cells that can reconstitute a patient's entire blood system or repair a damaged blood vessel, which could save countless lives in the years to come.
Therapies derived from these cells could one day be used in place of bone-marrow transplants for cancer treatments with cells that are more compatible with the patient's, reducing the risk of rejection.
Although the results from the Hopkins researchers still need to be tested in animals, this work shows a great deal of promise for the future.
