The official blog of the Lung Institute.
Advancements in Tissue Engineering and the Lungs
Reports of organs being grown in labs have generated a great deal of excitement surrounding the potential for use in the treatment of various diseases. These advances are especially promising for the treatment of chronic pulmonary conditions, including several that we treat at the Lung Institute, such as chronic obstructive pulmonary disease (COPD) and pulmonary fibrosis. While we are not quite to the point of engineering fully functioning lungs yet, research has led us to other great advances that could have a major impact on how we treat chronic pulmonary conditions. With cellular therapy, our goal at the Lung Institute is to improve patients’ quality of life. In this post, we’re going to discuss the status of lung bioengineering and where the research is heading within the field.
What is a bioengineered lung?
Today, cellular therapy and regenerative medicine are coming together and both will likely play an important role in the future of tissue engineering. Cellular medicine focuses on how our body’s cells affect various aspects of our health, including inflammatory and infectious disease, degenerative diseases, hereditary diseases, tissue engineering and regeneration. Cellular medicine is the study of cell lifecycles and how they communicate and move throughout the body. Regenerative medicine, on the other hand, refers to the replacement or regeneration of human cells, tissues or organs, to restore or establish normal function. Understanding how cells and tissues work together is key in being able to bioengineer new organs.
However, before we get into current possibilities and future predictions, let’s take a look at exactly what a bioengineered lung is. In total, there are three main definitions of bioengineering, but for our purposes, we’re referring to the development of artificial tissues or organs.
Bioengineering is the use of artificial tissue or organs to repair various parts of the body.
Artificial tissue refers to replacement organs or tissue that are grown in a lab to replace damaged or diseased tissue. In the lab, cell differentiation is used to turn a less specialized cell, or a stem cell, for example, into a more specialized cell type. In other words, a stem cell has the ability to turn into lung or skin tissue, and relies on communication from surrounding micro environment, or “niche”, other cells, or specialized cells, to tell it what type of cell it needs to become. Differentiation occurs when a cell turns from a less specialized cell into a more specialized cell.
We have already seen great advancements in tissue engineering for many organs, including bladders, small arteries, skin, cartilage, tracheas and other tissues. While these tissues have been engineered successfully, and some are even currently being used to combat diseases in humans, more complex organs are more difficult to replicate. Some of the tissues that make up organs such as the heart, lung and liver have been generated in a lab setting; however, we’re still a long way from being able to produce organs that are ready for implantation into a human patient.
“One of the better things that we’ve been able to do is what some people refer to as Organ-In-A-Dish technology,” said Jack Coleman, M.D., senior medical director of the Lung Institute. “They’ll take a Petri dish, put stem-cells in that dish along with various factors that then induce cell differentiation into different types of organ cells, and they can do that with some of the epithelial cells for the lung. What that means is they can create a structure similar to the alveoli. They can experiment with that organoid’s structure and function at the cellular level. The main thing they’re using that for is to determine the effects of new medications on various body tissues. It’s much cheaper and more humane than doing studies on many animals that would then have to be sacrificed or early studies with humans. We’re trying to figure out what medications will benefit or cause harm. Right now, I think that’s the most striking thing that we can do with differentiation. That and the ability to create at least part of the structure of the lung.”
What We Need to Have in a Functional Lung
Before we dive deeper into what’s holding us back from bioengineering lungs in humans, let’s first take a look at what is needed to have a functional lung. According to a study conducted by the Department of Pathology, Yale University School of Medicine: Extracellular matrix as a driver for lung regeneration. At a minimum, a lung should be able to accomplish the following:
- Maintain lung-specific cells that reduce surface tissue tension and have growth factors and cilia, or hair-like particles that keep the lungs clean of fluids and particles
- Act as a barrier to separate blood from air
- Provide a surface that facilitates the exchange of oxygen and carbon dioxide
- Allow blood to flow through the organ without clotting
- Be mechanically sound enough to allow for air to move in and out of the lungs and also be able to handle physiological stresses
Why Haven’t We Mastered the Bioengineered Lung?
With all of the medical advancements in the fields of regenerative medicine and cellular therapy, it can be confusing and frustrating when we realize that we are just not there yet. Yet, there is great promise for what the future holds. The extracellular matrix (ECM) is molecules secreted by cells that provide support to surrounding cells. The ECM is unique to every organ and will function differently. In fact, breakdown of the ECM in the lungs is a major reason why lung diseases are able to progress. Therefore, the use of cellular therapy shows great promise in regard to cell regulation and the reduction of inflammation. However, knowledge of the ECM composition in the lung is still evolving. In fact, it is highly likely that some variants of common structural proteins in the lungs have not even been characterized.
Further, much of the research that has been conducted has been done on rats and mice. However, there are major differences between species, including organ size, alveolar size and number, tissue density, cell numbers and composition. In other words, what works in mice and rats won’t necessarily work the same in humans.
“What we can do for a rat or mouse lung is not the same that we can do in a human lung,” said Dr. Coleman. “The vast majority of the literature that we have is on rat or mouse lungs, unfortunately. Roughly 35% of the physiologic response of rodent species can be translated to equivalent human physiologic response. That’s going to be one of the major hurdles that the Mayo Clinic is going to have to overcome. But, I am confident that they will do it.”
The Lungs are Complicated
The lung is an extremely complicated organ made up several distinct tissues that have varying functions in different areas. The lung is one of the more complex organs in the human body consisting of all four of the major tissue types, over 40 cell types giving a total of 1014 cells in the adult human lung that all have to be arranged in a very specific three-dimensional pattern to have a functional organ. “As an example, there are six different types of collagen in different parts of the lung. The question becomes, how do you make the collagen distribute that way in an artificial environment? We still haven’t figured that out yet,” said Dr. Coleman.
Different tissues play specific and often multiple roles, such as those having to do with elasticity, ventilation mucus production and clearance and gas exchange. Not only that, various tissue types hold different degrees of stiffness throughout the lungs or the same tissue type may have different degrees of stiffness depending on location within the lung. The issue lies in our current inability to direct cells to become different tissues that hold different functions in an artificial environment. Additionally, when applied in this way in an artificial environment, cells run the risk of growing in clusters resulting in a tumor.
Decellularization in Lung Transplants
The Mayo Clinic is currently conducting extensive research on the decellularization of donor lungs intended for transplantation. This could be a game changer for lung transplants, which currently have a high mortality rate.
“Lung transplant surgery itself is pretty straightforward,” said Dr. Coleman. “The problem is the body rejecting the organ and the medication that people have to take as a result. That’s what makes the survival rate so bad and quality of life in transplant patients so poor. At five years, reported mortality rates are as high as 50 percent, which is not very good.”
Recent research shows that donor lungs, also called native lungs, show promise because they already hold the shape, referred to as the scaffold, of the lung organ. Decellularization is when the lung tissue is stripped of the donor’s cells, which are what the lung transplant recipient’s body rejects, because their body recognizes cells from another person’s body as foreign objects.
Once the lung tissue is stripped of the donor’s cells, it is then implanted with cells from the recipient patient, therefore reducing the potential for rejection. However, the scaffolds need to retain many of the essential proteins that are present in the original organ that direct cells on where to go and how to differentiate. Because of this, decellularization is a delicate balance between removing the cells that we don’t want while retaining critical components that are needed to regain healthy lung function moving forward. The Mayo Clinic is working on this today, and this technology shows great promise for the future of lung transplants.
Looking Ahead at Bioengineering Lungs
“We’re years and years away from being able to engineer a lung,” said Dr. Coleman. “To work from scratch, trying to create a human lung, might be decades off, even centuries. But, in the meantime, we will continue to try to improve our ability to utilize local or systemic cell implantation techniques, to try and utilize Organ-In-A-Dish technology to create functional lung segments that could be grafted into damaged lungs and follow the progress of the decellularization of a donor lung project, which holds more promise today.”
Cellular therapy and regenerative medicine hold great promise in addressing chronic pulmonary conditions. If you or a loved one are interested in learning more about how cellular therapy may be able to slow the progression of pulmonary conditions, contact us today for more information.