Devising New Ways to Improve the Bioengineering of Blood Vessels

Imagine you’re building a house from scratch. You know the components you’ll need: foundation, framework, walls, a roof, plumbing and electricity, to name a few.

But there’s a lot more that goes into the process. How do you wire each room for electricity and connect the plumbing to sinks and showers? How do you hook up to nearby utility services? In short, how can you combine each of these components into a fully functional unit?

In a way, this is the same challenge facing researchers who are working to bioengineer new organs. While they have been successful in reseeding stripped down organs with new cells, there’s still a long way to go before the organ operates as a functional unit.

Wafa Altalhi, PhD, a postdoctoral fellow in the Ott Lab at Massachusetts General Hospital’s Center for Organ Engineering, is working on strategies to rebuild what could be considered the plumbing system of an organ—the blood vessels that bring nutrients to its cells and connect it to the rest of the body.

Altalhi, a Saudi Arabian scientist, was one of four postdoctoral female scientists to receive the L’Oreal-UNESCO Women in Science Middle East Fellowship in 2019. The fellowship is a global program that recognizes outstanding women in science and highlights their contributions to scientific progress.

The Promise and Challenges of Bioengineering

Bioengineered organs could fill a critical medical need by providing patients in need of a transplant by creating new organs that are populated with their own cells.

In the future, this could reduce the demand and wait times for donor organs and (in a best case scenario) eliminate the need for transplant recipients to take immunosuppressive drugs.

To create a bionengineered organ, researchers first take a donor organ that is not viable for transplant and strip it of its existing cells so that only the extracellular matrix (cartilage framework) remains.

They then take cell samples from a would-be organ recipient, convert them into multipurpose starter cells called induced pluripotent stem cells (iPCS), and prompt the cells to differentiate into the various cell types that comprise the organ.

The cells are then seeded back onto the matrix in a way that replicatse the structure of a fully formed organ. But it’s not enough just to put the pieces back together. To be viable for transplant, the organ has to be able to thrive within the body, and that requires a steady and reliable blood supply.

Altalhi is working on several projects designed to improve the viability of bioengineered blood vessels, including:

  • Perfecting cell differentiation techniques to more accurately the replicate the different types of cells within blood vessels
  • Creating a media culture (liquid nutrients) that best support the growth of cells in the lab
  • Identifying the best way to flow that media culture through the cells once they are seeded onto the lung so they stay viable as the various parts of the organ come together
  • Devising a strategy to introduce the blood vessel cells to shear stress—the pressure caused by liquid flow—so they are ready to accommodate blood flow once the organ is transplanted

While the work is exciting and the potential is huge, she knows there’s a long road ahead. “Although we’re closer than before, we are not even near making a complete organ that resembles what we are born with,” she says. “It’s a work in progress but it has a lot of promise.”

From Saudi Arabia to Mass General

Althali, who comes from a large family with an interest in science and medicine, was initially drawn to medical research to find ways to improve vascular bypass surgeries and reduce ischemia (loss of blood flow) complications related to diabetes, which has a high prevalence in Saudi Arabia and worldwide.

Her scientific journey has taken her to graduate school at the universities of Ottawa and Toronto before coming to Mass General to work as a postdoctoral fellow in the Ott Lab.

“Mass General has been my best experience so far,” she says. “I see scientists like Dr. Ott who sits at the intersection of academia, field work and entrepreneurship, and its inspiring that people are so committed to translating their science to products that can help patients.”

“It’s rewarding to investigate science for the sake of knowledge–but translating that knowledge into a product for patients is helping more.”

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