Friday, 5 April 2013

Researchers create functional human capillaries from adult stem cells

One of the biggest problems faced by scientists who try to grow organs in the lab, is forming blood vessel networks that nurish and keep the tissues alive. Today, researchers from the University of Michigan (UM) announced some very promising findings that may help overcome this obstacle. The study also has implications in the treatment of conditions that affect the circulatory system, like diabetes.

Andrew Putnam, chief author of the study, explains why the ability to form functional blood vessels is so important tissue engineering:

"If you don't nourish it with blood by vascularizing it, it's only going to be as big as the head of a pen."


Currently, there are two main approaches that researchers use to grow new capillaries, the smallest blood vessels our body has (5-10 μm in diameter), with their main role being to exchange water, oxygen, carbon dioxide, and other nutrients and waste chemical substances between blood and surrounding tissues like muscles and organs.

The first method employed by scientists is to use a mixture of drugs that induces nearby vessels to grow new "branches" of blood vessels. The second method is to inject cells in a scaffold which is then placed to the area the researchers wish to grow new capillaries.


Cross section of a capillary.
Cross section of a capillary


In this study, Putnam and his team went with the second method and used endothelial cells with a scaffold containing a protein called "fibrin". Fibrin is a fibrous, non-globular protein, heavily involved in the blood coagulation process (blood clotting). Putnam says that the cells seem to know "what to do",  as studies on animals have shown that a simple injection is usually enough for new vessels to grow in a matter of days.

However, this is not always the case and in certain studies the cells had failed to form new vessels. In this study, Putnam's team tried to explore why this happens. What they first noticed, is that many researchers had used a "mishmash of support cells" without defining which ones brought the best results. And this is where the UM team decided to focus.

During the study, the researchers experimented on three "recipes" of blood vessel starter solutions, each one mixed with a different type of supporting cell type:
  • Lung fibroblasts
  • Adult stem cells from adipose tissue (fat) 
  • Adult stem cells from bone marrow
  • No supporting cells (control)

Then, the solutions where injected separately under the skin of mice, which were closely followed for 14 days for any signs of blood vessel formation. The mice were also injected with a special dye that helped researchers observe how the new capillaries grew, held blood and if they connected with the existing blood vessel network.

The control solution and the one containing lung fibroblasts gave the worst results. The capillaries formed by those two were immature, badly formed and were "leaky". On the other side, both of the adult
stem cell solutions resulted in fewer but healthy, sturdier, well formed, human capillaries that didn't leak. The study also indicates that the adult stem cells may have the capacity to develop into the cells comprising smooth muscle tissue which supports larger blood vessels. Finally, the researchers note that the adult stem cells were equal, regardless of their original environment.

"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." said Putnam

Putnam hopes that sometime in the future doctors will use autologous stem cells (taken from the patient himself) and use them to form new blood vessels in the area needed.


 Andrew Putnam talking about his work

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Reference
Grainger, S., Carrion, B., Ceccarelli, J., & Putnam, A. (2013). Stromal Cell Identity Influences the Functionality of Engineered Capillary Networks Formed by Co-delivery of Endothelial Cells and Stromal Cells Tissue Engineering Part A, 19 (9-10), 1209-1222 DOI: 10.1089/ten.tea.2012.0281

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