Patients' own stem cells could build better blood vessels, improve tissue engineering
Washington: Researchers from the University of Michigan (UM) have reportedly discovered a new way to overcome one of the major obstacles to growing new organs-replacement hearts, lungs and kidneys.
Those replacement organs often fail because of the difficulties associated with building blood vessels in order to keep their tissues alive.
Andrew Putnam, U-M associate professor of biomedical engineering, and his colleagues have revealed why one of the leading approaches to building blood vessels isn`t consistently working: It`s making leaky tubes. They also demonstrated how adult stem cells could solve this problem.
Today, biomedical researchers are taking two main approaches to growing new capillaries, the smallest blood vessels and those responsible for exchanging oxygen, carbon dioxide and nutrients between blood and muscles or organs.
One group of researchers is developing drug compounds that would signal existing vessels to branch into new tributaries. These compounds-generally protein growth factors-mimic how cancerous tumor cells recruit blood vessels.
The other group, which includes the U-M team, is using a cell-based method. This technique involves injecting cells within a scaffolding carrier near the spot where you want new capillaries to materialize. In Putnam`s approach, they deliver endothelial cells, which make up the vessel lining and supporting cells. Their scaffolding carrier is fibrin, a protein in the human body that helps blood clot.
"The cells know what to do. You can take these things and mix them and put them in an animal. Literally, it`s as easy as a simple injection and over a few days, they spontaneously form new vessels and the animals` own vasculature connects to them," Putnam said.
But it turns out these vessels don`t always thrive. The U-M team aimed to figure out why. In reading previously published findings, Putnam noticed that researchers used "a mishmash of support cells," and the field had paid little attention to which ones work best. So that`s where he and his colleagues focused.
In their experiments, they mixed three recipes of blood vessel starter solutions, each with a different commonly used supporting cell type: lung fibroblasts, adult stem cells from fat and adult stem cells from bone marrow. They also made a version with no supporting cells at all. They injected each solution under the skin of mice, and allowed the new blood vessels to form over a period of two weeks.
At various points in time, they injected a tracer dye into the animals` circulation to help them see how well the engineered capillaries held blood, and whether they were connected to the animals` existing vessel networks.
The researchers found that the solution with no support cells and the one with the lung fibroblasts produced immature, misshapen human capillaries that leaked. They could tell because the tracer dye pooled in the tissue around the new vessels. On the other hand, the solutions with both types of adult stem cells gave rise to robust human capillaries that kept blood and dye inside them.
They noted that one popular method biomedical engineers use to check the success of their efforts-counting blood vessels-might not be an ideal measure. The adult stem cell solutions produced fewer blood vessels than the others, in one case less than half. But the vessels they did build were stronger.
And upon further analysis, the researchers found evidence that the adult stem cells may be able to differentiate into the kind of mature, smooth muscle cells that support larger blood vessels.
"The adult stem cells from fat and bone marrow both work equally well. If we want to use this clinically in five to 10 years, I think it`s crucial for the field to focus on a support cell that actually has some stem cell characteristics," Putnam said.
Down the road, Putnam envisions that doctors could get these support cells from individual patients themselves-either from their bone marrow or fat-and then inject them near the site where the new blood vessels are needed.
A paper on the findings has been published online in Tissue Engineering Part A, and will appear in a forthcoming print edition.