Making Organs from Scratch

Cutting-edge. Young.  Ambitious. These words can describe many remarkable people in different fields. In the world of regenerative therapeutics, they describe Ali Khademhosseini. Having already racked up several prestigious awards, such as the Curtis McGraw Award of the American Society for Engineering Education, Presidential Early Career Award for Scientists and Engineers (PECASE), and the Society for Biomaterials (SFB) Young Investigator Award, the 36-year-old has made amazing strides in tissue engineering.

His latest endeavor could come from the pages of Frankenstein or science fiction, captivating as it is jaw-dropping. Khademhosseini's lab is buzzing with scientists all focused on one goal--creating pieces of living tissue that will one day redefine the landscape of organ transplantation and drug discovery.

How would you describe your work? 

We are trying to address one of the major limitations in medicine, which is the lack of available transplantable organs. To do this, we aim to combine expertise from disciplines such as engineering, materials science and biology to regenerate artificial tissues that can be transplanted.  Furthermore, the ability to make human tissues outside the body can be used to test for safety and efficacy of drugs prior to expensive clinical trials.

Can you explain  how you regenerate artificial tissues?  

Cells in the body deposit a lot of matrix. Thus, they can actually modify their surrounding environment and basically put down 'pillows' or 'cushions' for themselves.  We aim to engineer materials that can create the same kind of 'happy' environment for the cells. This can be done through making materials that swell in water to form Jell-O-like gels. We can integrate cells with these Jell-O-like materials. In most cases, the cells degrade the gel and deposit their own matrix. So, this will allow us to have a template that will help the cells form the resulting tissues. 

How is your work different from other work being done in regenerative therapeutics?  

The majority of approaches today utilize large pieces of materials. The problem is that in these large pieces, the cells do not generate the same kind of functional structures that they do in our bodies. Cells themselves are between 10 and 100 micrometers (smaller than the width of a hair strand). Thus, it is important that we engineer the environment of the cells at the same length scales as the cell. That way, if you have different cell types next to each other, you can literally engineer the surrounding matrix so each cell sees what they like to see. This is something that not too many other people have been able to do.

What successes have you achieved in your lab?  

We have been able to generate a number of different types of tissue structures that have maintained their functions fairly well in tissue culture. For example, we have been able to generate artificial heart tissue that can spontaneously beat, resembling natural heart tissue. Also, we have been able to generate small artificial blood vessels. Furthermore, we have worked in trying to differentiate stem cells into therapeutically useful cells. For example, we have worked with collaborators at BWH to direct the differentiation of endothelial progenitor cells, which normally circulate in the bloodstream to make artificial blood vessels.

What do you consider to be some of the challenges in creating tissues?

A key challenge in tissue engineering is that while some of the simpler tissues, like skin, bone or cartilage, have had a much easier time making it to the clinic. More complex tissues, such as the heart and liver, have not been as successful. Since the structure and function are so related, it is important to have the right kind of microenvironment for the cells to be able to direct tissue formation. To address this issue, we have been combining knowledge from various scientific fields to come up with new approaches that can be used to fabricate complex biological systems.

When do you think the work in your lab can be applied in a clinical setting?  

There are still a great deal of challenges in trying to make regenerative therapeutics readily available clinically. It has happened to some degree for some of the simpler tissues. But it is far away in reaching its full potential. I hope to translate some the things we are trying to do in the lab-directing differentiation of stem cells or putting these cells in the right kind of architecture and geometries to generate functional tissues-to make a clinical impact.  

What do you find exciting about your field?  

We are trying to create ways to make different tissue structures assemble to generate functional heart tissue. Of course it is far away into the future, but I think these smaller pieces of tissue will have a much faster way of making it to the clinic. As we get good at making pieces of tissue, then we can start putting them together to make fully functional organs. I think that making tissues is already a reality in a different number of cases and more examples are being described every day. It is a highly fast paced and stimulating scientific area that is at the interface of many established disciplines. So it is very exciting to be in this field.

How did you get into the field of tissue engineering?  

My background is in engineering. For students majoring in the field of chemical engineering, the typical thing to do was to go into the oil or other developed industries. Of course there are opportunities to make an impact in these industries, but they are usually incremental, which did not interest me much. Therefore, when I had the opportunity to get involved in tissue engineering, I thought it was amazing to be able to use the principles of engineering and materials sciences and combine it with biology to come up with totally new and radical ways to treat patients and push medicine forward. So I was very lucky to get exposed to this kind of research early in my training.

What do you like about working at BWH?  

I think Brigham and Women's Hospital is an amazing place to work because researchers like me can work closely with clinicians. Such close connections are something that you do not see in many other places. It is just an incredible experience to be able to do research in very close proximity with people who are doing the surgery, or who are doing different kinds of imaging or treating patients on a daily basis. So I think that it is a unique experience. I've been here a few years and seen a steady rise in both the quantity and quality of the research at Brigham and Women's Hospital. It is an incredible and wonderful place to work.