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An ‘Off-the-Shelf’ Replacement for Damaged Blood Vessels?

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human acellular vessel
Credit: Humacyte, Inc., Durham, NC

The object in the image above might look like an ordinary plastic tube. But this tube is neither plastic nor ordinary. It’s a bioengineered replacement human blood vessel that could one day benefit people who receive kidney dialysis or undergo coronary bypass surgery.

It’s called a human acellular vessel (HAV), and an NIH-funded team, led by Heather Prichard, Humacyte Inc., Durham, NC, grows these acellular vessels. They can run up to about 16-inches long with a diameter of 0.2 inches, which is well within the range of a human blood vessel.

Prichard and team start with a lightweight and biodegradable polymer mesh. They then seed the mesh scaffold with cells taken from human donor tissue within a 3D bioreactor system in the lab. The system is specially designed to provide nutrients and mechanical pulsations similar to those present in an intact human circulatory system.

After incubating the growing vessels for eight weeks, the researchers remove all the living cells, leaving behind mostly human collagen, a fibrous protein and major structural component of a blood vessel wall. It forms a non-living, replacement vessel that retains the physical and mechanical integrity of a human blood vessel. But, because these HAVs don’t have cells, they potentially can be surgically implanted into any human patient without risk of an immune reaction.

As reported recently in Science Translational Medicine, the best part is what happens after an HAV is implanted into the body [1]. The patient’s own cells infiltrate the HAVs. Over the course of many weeks, these cells produce multiple layers of living tissue to transform the acellular HAV into a functional, living blood vessel.

So far, HAVs have been tested in more than 240 people with end-stage kidney failure. The HAVs were implanted into the upper arms of participants and remained there from 16 to 200 weeks while these patients underwent dialysis three times per week to filter waste products from their blood. The early results indicate these bioengineered blood vessels were safe and fully functional. More research, though, will be needed to ensure that’s indeed the case.

For people who receive kidney dialysis, doctors now typically access the vasculature by linking an artery to a vein under the skin of the arm, making an “AV fistula.” But doctors can also use the HAV tube to make the needed connection.

What’s potentially game changing about HAVs is they offer the same “off-the-shelf” ease of a plastic tube but with the advantages of living tissue. Those advantages include the ability to fight infection and self-heal from the inevitable injury that comes with repeated needle pokes.

Though most of the work to date has focused on people undergoing kidney dialysis, an ongoing clinical trial is testing the potential of HAVs to improve blood flow when surgically implanted into the legs of patients with peripheral arterial disease [3]. Prichard also sees potential for HAVs in heart surgery. For example, HAVs might be useful during coronary bypass surgery to repair a narrowed or blocked blood vessel. They could also be used to replace blood vessels damaged or missing due to congenital defects or traumatic injuries. Not bad for an object that looks like an ordinary plastic tube.

References:

[1] Bioengineered human acellular vessels recellularize and evolve into living blood vessels after human implantation. Kirkton RD, Santiago-Maysonet M, Lawson JH, Tente WE, Dahl SLM, Niklason LE, Prichard HL. Sci Transl Med. 2019 Mar 27;11(485).

[2] Kidney Disease Statistics for the United States. National Institute of Diabetes and Digestive and Kidney Diseases/NIH

[3] Humacyte’s HAV for Femoro-Popliteal Bypass in Patients With PAD. Clinicaltrials.gov

Links:

Safety and Efficacy of a Vascular Prosthesis for Hemodialysis Access in Patients With End-Stage Renal Disease (ClinicalTrials.Gov)

Hemodialysis (National Institute of Diabetes and Digestive and Kidney Diseases/NIH)

Tissue Engineering and Regenerative Medicine (National Institute of Biomedical Imaging and Bioengineering/NIH)

Humacyte (Durham, NC)

NIH Support: National Heart, Lung, and Blood Institute


Cool Videos: Spying on Cancer Cell Invasion

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Spying on Cancer Cell Invation

If you’re a fan of the Mission: Impossible spy thrillers, you might think that secret agent Ethan Hunt has done it all. But here’s a potentially life-saving mission that his force has yet to undertake: spying on cancer cells. Never fear—some scientific sleuths already have!

So, have a look at this bio-action flick recently featured in the American Society for Cell Biology’s 2015 Celldance video series. Without giving too much of the plot away, let me just say that it involves cancer cells escaping from a breast tumor and spreading, or metastasizing, to other parts of the body. Along the way, those dastardly cancer cells take advantage of collagen fibers to make a tight-rope getaway and recruit key immune cells, called macrophages, to serve as double agents to aid and abet their diabolical spread.


Snapshots of Life: Visualizing Blood Vessels

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Blood Vessels

Credit: Christopher V. Carman and Roberta Martinelli, Harvard Medical School, Boston

This might look a bit like a fish net, but what’s actually caught in this image is the structure of the endothelium—the thin layer of cells lining your blood vessels that controls the flow of molecules in and out of the bloodstream. The red lines are the actin filaments that give each endothelial cell its shape, while the purple are proteins called cadherins.

Most of the time, the actin “ropes” and cadherin “glue” act together to form a tight seal between endothelial cells, ensuring that nothing leaks out of blood vessels into surrounding tissue. However, when endothelial cells sense an infection or an injury, the cadherins open gaps that allow various disease-fighting or healing factors or cells present in the blood to breach the barrier and enter infected or injured tissue. After the infection subsides or wound heals, the gaps close and the blood vessel is once again impenetrable.