Newly designed “bioink” get us one step closer to 3D printed organs

3D bioprinted small airways made out of two cell types (blue and yellow) remain open over time.

3D printing technology has revolutionized the way we think about creating things with complex designs with the simple click of a button. The ability to be able to give a computer a specific set of instructions and hit “print” is appealing in this modern era of instant gratification and convenience. In the regenerative medicine field, there has been a specific interest in using this type of technology to create vital organs for transplants, something that would be extremely helpful to those anxiously waiting for a donor.

Researchers at Lund University in Sweden have gotten one step closer to making 3D organ printing a reality by designing a new type of “bioink” which allows small human-sized airways to be 3D-bioprinted using patient cells for the first time. For this project, the researchers focused on the lungs but the proof of concept could be applicable to other types of organs.

Like many other debilitating conditions, there is no cure for chronic lung disease and the only end-stage option for patients is lung transplantation. However, there are not enough donor lungs to meet clinical demand.

The researchers first designed a new type of “bioink”, which is a printable material made with cells. The “bioink” was made by combining materials made from seaweed, alginate, and an extracellular matrix made from lung tissue. The “bioink” is important because it supports the bioprinted material over several stages of its development towards tissue. The researchers used it to 3D-bioprint small human airways containing two types of cells found in human airways.

Blood vessel infiltration in the 3D bioprinted constructs.

The team then used a mouse model closely resembling the immunosuppression used in patients undergoing organ transplantation and transplanted the newly created cells inside the mice. What they found was remarkable in that the 3D-printed airways made from the new “bioink” were well-tolerated and supported new blood vessels.

Although more work needs to be done in order to perfect this technique, these results provide a pivotal step forward in one day making bioprinting organs a reality.

In a press release, Dr. Darcy Wagner, senior author of this study, expresses optimism about their findings.

“We hope that further technological improvements of available 3D printers and further ‘bioink’ advances will allow for bioprinting at a higher resolution in order to engineer larger tissues which could be used for transplantation in the future.”

The full results of this study were published in Advanced Materials.

‘Mini lung’ model shows scientists early stages of new coronavirus infection

Representative image of three-dimensional human lung alveolar organoid showing alveolar stem cell marker, HTII-280 (red) and SARS-CoV-2 entry protein, ACE2 (green)
Image Credit: Jeonghwan Youk, Taewoo Kim, and Seon Pyo Hong

The development of organoid modeling has significantly expanded our understanding of human organs and the diseases that can affect them. For those unfamiliar with the term, an organoid is a miniaturized, simplified version of an organ produced that is also three dimensional.

Recently, scientists from the University of Cambridge and the Korea Advanced Institute Science and Technology (KAIST) were able to develop ‘mini lungs’ from donated tissue and use them to uncover the mechanisms behind the new coronavirus infection and the early immune response in the lungs.

SARS-CoV-2, the name of the coronavirus that causes COVID-19, first appears in the alveoli, which are tiny air sacs in the lungs that take up the oxygen we breathe and exchange it with carbon dioxide.

To better understand how SARS-CoV-2 infects the lungs and causes COVID-19, the team used donated tissue to extract a specific type of lung cell. They then reprogrammed these cells to an earlier stem cell-like state and used them to grow the lung organoids.

The team then infected the ‘mini lungs’ with a strain of SARS-CoV-2 taken from a patient in South Korea who was diagnosed with COVID-19 after traveling to Wuhan, China.

Within the newly infected lung organoids, the team observed that the virus began to replicate rapidly, reaching full cellular infection in just six hours. Replication allows the virus to spread the infection throughout the body to other cells and tissue. The infected cells also began to produce interferons, which are proteins that act as warning signals to healthy cells, telling them to activate their antiviral defenses. After two days, the interferons triggered an immune response and the cells started fighting back against infection. Two and a half days after infection, some of the alveolar cells began to disintegrate, leading to cell death and damage to the lung tissue.

In a news release, Dr. Joo-Hyeon Lee, co-senior author of this study, elaborates on how he hopes this study can help more vulnerable sections of the population.

“We hope to use our technique to grow these 3D models from cells of patients who are particularly vulnerable to infection, such as the elderly or people with diseased lungs, and find out what happens to their tissue.”

The complete study was published in Cell Stem Cell.

CIRM has funded two discovery stage research projects that use lung organoids to look at potential treatments for COVID-19. One is being conducted by Dr. Brigitte Gomperts at UCLA and the other by Dr. Evan Snyder at the Sanford Burnham Prebys Medical Discovery Institute.

Stem cell clinical trial for COVID-19 patients gets emergency federal approval

Dr. Camillo Ricordi, principal investigator of a stem cell trial for COVID-19 at the
University of Miami Miller School of Medicine
Image Credit: Diabetes Research Institute Foundation Website

A team of doctors at the University of Miami (UM) Miller School of Medicine received emergency approval from the U.S. Food and Drug Administration (FDA) to conduct a clinical trial to treat patients with severe lung inflammation as a result of COVID-19.

The doctors will use stem cells obtained from umbilical cord blood and will deliver them via intravenous (IV) infusion to 12 patients. IV infusions of stem cells are known to travel directly to the lungs, the location where damage is being caused in severe cases of COVID-19. When a patient contracts the virus, their body produces cytokines, proteins that play an important role in the immune response. Unfortunately, having too many cytokines, known as a “cytokine storm”, leads to a severe immune reaction which causes damage to the lungs.

Umbilical cord stem cells are known to contain anti-inflammatory properties and the UM team hopes that the treatment can alleviate the “cytokine storm” and lung inflammation. The rationale for this approach is based off of a small study in China where seven patients received this treatment and showed improvement in lung function and symptoms. Despite these positive results, it is important to note that this trial is in very early testing and will need to demonstrate significant improvement in larger patient groups.

In an article from the Miami Herald, Dr. Camillo Ricordi, principal investigator of the trial, discusses how the results of the therapy will be observed very quickly if successful.

“This is not a study you have to follow up with in six months, because the results are immediate. In one week, you know: Is it working or not?”

In the same article from the Miami Herald, Dr. Ricordi discusses how the team of UM researchers and doctors are preparing to expand the trial to more patients if it is successful.

“We are already doing cell production anticipating this. We are planning for success, but of course we have to see how it does with our patients.”