End-stage lung diseases have very high morbidity and mortality rates. Chronic obstructive pulmonary disease (COPD) was the third leading cause of death in the United States in 2015, and it remains incurable. Lung cancer is also taking many lives, and the only highly effective treatment for end-stage lung failure at this time is orthotopic transplantation – transplanting a donor organ into the same anatomical position as the failing organ.
Unfortunately, there is a donor lung shortage, made worse by the fragility of lungs during procurement and transplantation. Additionally, after a lung transplant, a patient is required to be immunosuppressed so their body doesn’t reject the organ, opening the door to potential other health complications. Researchers are looking for a solution to this medical challenge – and exploring the option of using decellularized porcine lung scaffolds as a potential solution (as well as a research tool) in their regenerative pulmonary research.
Donor Lung Shortage and Solutions
Lung transplant remains one of the only (if not the only) highly effective treatments for end-stage lung disease. Although surgery techniques and post-operative care are improving, there is still a severe lung donor shortage. One recent study published findings that in North America alone, 15% of adult patients in need of lung transplants pass away or are removed from the transplant wait list due to increasing sickness that prevents transplant viability. This shortage of donor lungs is partially due to strict donor criteria. The ideal lung donor is between the ages of 20 and 45, has never smoked, has a clear chest x-ray, a clean bronchoscopy, and other clean health records. This means that less than 30% of available donor lungs can be used in transplants.
These researchers propose expanding donor criteria, or at least allowing patients to choose lungs from older donors or those with unusual causes of death. These ‘imperfect’ lungs, by current medical standards, could still help save lives in a donor lung shortage. However, additional options are being considered to address the donor lung shortage – including the potential use of decellularized porcine lung scaffolds (at the very least as research tools).
Decellularization: Definition, Challenges, and Methods
Decellularization is the process of stripping away living cells from an organ, such as a human or porcine lung, and leaving behind the Extracellular Matrix (ECM). The ECM is a protein frame that keeps the lung structure and elastic recoil, providing “biological scaffolds” for lung tissue engineering. This method has been tested in multiple experiments as researchers seek to find a solution for the donor lung shortage affecting end-stage lung disease mortality rates.
One of the challenges with decellularization is the fact that effective cell removal can sometimes damage critical matrix components in the ECM. As the detergent removes cells, it can also remove and damage glycoproteins and proteoglycans. Some damage is worse than others, ranging from impaired cell engagement to complete loss of tissue strength. To move forward with decellularized porcine lung scaffolds in regenerative pulmonary research, researchers would first have to find an effective decellularization method that doesn’t cause too much damage to the ECM.
Recent tests have observed multiple decellularization methods, beginning their testing by slicing human and porcine lungs into sheets. Researchers then applied detergents and observed the composition, structure, and biomechanical changes to the lungs through the decellularization process. Over a period of one week, they also watched to evaluate the viability, growth, and metabolic activity of the samples, determining if the ECMs were viable for repopulation and transplant.
Multiple detergents were tested, including Triton X-100, sodium dodecyl sulfate (SDS), sodium deoxycholate (SDC), and 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS). The most effective decellularization agent was found to be CHAPS, although researchers noted that they believe the ideal decellularization process would likely use multiple detergents combined. The goal is to preserve the ECM while still removing cells in the process.
Porcine Lung Scaffolds in Decellularization Tests
In recent studies, researchers found that preliminary testing of porcine lung decellularization was successful. The protocol described above produced translucent scaffolds with no significant differences between tissue samples. The microarchitecture of the lung was preserved, determining that the decellularization process was effective, and a viable solution to keep exploring.
These studies were performed on whole lungs from Yorkshire pigs (ranging from 200-300 grams total weight) and accessory lobes (ranging between 15-21 grams total weight). In addition to the microarchitecture remaining intact, the decellularized tissue kept its microstructure similar to native tissue, without harming the structure of the septae, vasculature, and upper airways, as well as the majority of collagen type I and elastin fibers. The success of these studies, along with the recent research into the best decellularization methods, is a significant step forward in regenerative pulmonary research.
Significance of Porcine Lungs in Regenerative Pulmonary Research
Research finds that decellularized porcine lungs (using the CHAPS detergent process) have ECM scaffold properties closely resembling human lungs. This is a significant breakthrough for research and medical advancement, as porcine lungs may be able to be used for screening and engineering testing. Data suggest that this decellularization protocol results in an acellular scaffold very similar to native tissue, with strong results in the areas of collagens, elastin, fibronectin, and laminins.
Another step in this research process is to determine if decellularized porcine lungs are viable to recellularize effectively, and that was observed in the same research study mentioned above. Decellularization is only considered effective if it is adequate for cell seeding. It was found that the Triton X/SDC I method produced ECMs more suitable for superior engraftment, moving this area of medical knowledge forward.
Porcine lungs continue to be a valuable model system in this area of study. Researchers’ ultimate goal is to produce transplantable lungs, while also utilizing porcine lungs for testing along the way. Porcine lungs are more effective than other options because the scaffold and structure closely resemble human lungs, making them a helpful comparison to study. As medical researchers continue advancing this area of science, porcine lungs play a crucial role in the race against time to save the lives of those with advanced end-stage lung diseases.
Advancing Regenerative Pulmonary Research
As medical researchers continue moving forward with new studies and advancements in this area, porcine models play an important role in accelerating innovation and helping find solutions to difficult-to-treat diseases.
At Tissue Source, we are proud to provide high-quality, ethically sourced porcine lungs for clinical, research, and educational use. These lungs are helpful in the research happening around decellularized porcine lung scaffold viability. We provide clients with:
- Customized Solutions: Whether you’re looking for whole porcine lungs or other porcine organs, we offer flexible options to meet your needs.
- Traceability and Quality Assurance: We can provide traceability to individual animals as needed, or economical options for less stringent requirements.
- Commitment to Innovation: We are committed to providing ethically sourced, meticulously processed porcine lungs, organs, and other tissues that meet the highest medical, scientific, and educational research standards.
Contact Tissue Source today to learn how our customizable solutions can support your next project or research study.