Bio-engineered lungs: the first successful organs made in lab
What if you could make a creature that was half- human or half- animal? Do you use it to fly away? What if you could use it to save lives? That is what some scientists are trying to do by injecting human stem cells into animal embryos. Isn’t it magical?
At present, lung diseases such as emphysema, interstitial fibrosis, and pulmonary vascular diseases have become the third leading cause of death worldwide. The European Union spends over EUR380 billion annually for respiratory diseases. As currently discovered, the only option for end-stage respiratory disease is lung transplantation. In Europe, approximately 2000 lung transplants are performed each year with the same number or more patients awaiting transplantation. However, limited donor lung availability, long-term side effects after transplantation, and graft rejection are major barriers to lung transplantation being a panacea. Bioengineered lungs are an exciting and emerging solution that ultimately aims to create lung tissue and organs for transplantation.
The team with Dr. Joan Nichols, a Professor of Internal Medicine, Microbiology and Immunology at the University of Texas Medical Branch in Galveston became the first to bioengineer a human lung, by implanting a single-lab-built lung into a pig. The transplantation was based on seeding stem cells on decellularized lung scaffolds.
There are two major components to building an organ; the structure and the right cells on that structure. The research team was able to tackle both parts of the problem. Generally, the lung consists of at least 40 different resident cell types; all of which are necessary for its optimal functioning. These cells reside on and within an extracellular matrix (ECM) comprised of different regional combinations of ECM proteins and glycosaminoglycans (e.g. proteoglycans and hyaluronan) that act together as a scaffold to not only provide structure, but also to help direct repair and regeneration following injury (de Santis, M. M., Bölükbas, D. A., Lindstedt, S., & Wagner, D. 2018). In this experiment, first the researchers used a lung from an unrelated pig as a donor organ and stripped it of its cells, leaving a scaffold. The method of removing cells from its scaffolds is called decellularization. The decellularization process aims to remove the cellular material using a detergent and sugar solution without affecting the scaffold structure, ECM composition, and biological activity of the ECM components.
The transplantation takes place after the cells which are combined with a matrix made of natural or synthetic materials have grown ex-vivo to restore or improve the lung’s main function. Thus, researchers created four protein scaffolds, each of which was soaked in a bioreactor containing a mix of nutrients. Each bioreactor provided the organ with growth factors, media, and mechanical stimulation similar to the function of a placenta. Next, the cells from the recipient pig lungs were added to each scaffold with a cocktail of nutrients and allowed to develop for 30 days. During this period, scaffolds were infused with nanoparticles, delivering a special concoction of growth factors that include platelet-rich plasma, fibroblast growth factor 2 (FGF2), and keratinocyte growth factor (KGF). Finally, something resembling a baby lung was created. Before transplantation, the research team reconstituted an immune system in the newly bioengineered lungs, by replenishing with alveolar macrophages which clean out pathogenic and harmful particles that pollute the respiratory tract and infusing it with a serum made up of pig blood cells.
When the lungs were ready, they transplanted bioengineered lungs though immature into the four recipient pigs where they hoped it would continue development and mature. To study the progress of the bioengineered lungs, they euthanized the animals at different times: 10 hours, two weeks, one month, and two months after transplantation. Bioengineered lungs continued to develop after the transplantation without requiring the addition of exogenous growth factors to drive cell proliferation or lung and vascular tissue development. The bacterial community of the native lung was seeded and colonized on the sterile bioengineered lung. Within two weeks, the transplanted lungs began to develop networks of blood vessels essential to survive. After two months, the lab-grown lungs in the recipient pigs had grown well. The experiment was successful, showing no evidence of pulmonary edema and no sign of rejection of the transplanted organs.
However, a big question lingered on how well the bioengineered lungs deliver oxygen; whether the blood oxygen levels of pigs were holding at 100% because each pig still had one of its own fully functioning lungs. The researchers feared that the implanted organs were too underdeveloped to risk stopping each research animal from breathing on its original lung, to test the lab-grown one in isolation. Therefore, experimentation of bio-engineered lungs with long-term survival, the maturation of tissues and the critical gas exchange capacity has been handed over to future researchers.
References
- CBC Radio. (2018) Lab grown lungs are transplanted in pigs today, they may help humans tomorrow. Derived from https://www.cbc.ca/radio/quirks/dec-29-2018-water-on-mars-lab-grown-lungs-and-more-the-biggest-science-stories-of-2018-1.4940811/lab-grown-lungs-are-transplanted-in-pigs-today-they-may-help-humans-tomorrow-1.4940822
- de Santis, M. M., Bölükbas, D. A., Lindstedt, S., & Wagner, D. (2018). How to build a lung: latest advances and emerging themes in lung bioengineering. European Respiratory Journal, 52(1), 1601355. https://doi.org/10.1183/13993003.01355-2016
- Gonzalez, R. (2018, August 1). Bioengineers Are Closer Than Ever To Lab-Grown Lungs. Wired. https://www.wired.com/story/four-successful-bel-transplants/
- Prakash, Y. S., Tschumperlin, D. J., & Stenmark, K. R. (2015). Coming to terms with tissue engineering and regenerative medicine in the lung. American journal of physiology. Lung cellular and molecular physiology, 309(7), L625–L638. https://doi.org/10.1152/ajplung.00204.2015
- Pierce, S. (2019, August 28). Bioengineered lungs: How long from pigs to people? TMC News. https://www.tmc.edu/news/2019/06/bioengineered-lungs-how-long-from-pigs-to-people/
- Tsuchiya, T., Sivarapatna, A., Rocco, K., Nanashima, A., Nagayasu, T., & Niklason, L. E. (2014). Future prospects for tissue engineered lung transplantation: decellularization and recellularization-based whole lung regeneration. Organogenesis, 10(2), 196–207. https://doi.org/10.4161/org.27846
