Many of us have contemplated buying a reconditioned phone. It might be that bit older but it has a new screen and works as well as those in the shop-front. I’m not sure, however, that any of us have thought of investing in a reconditioned liver – but it could be coming to a body near you.
Researchers based in São Paulo’s Institute of Biosciences have been developing a technique to create and repair transplantable livers. The proof-of-concept study published in Materials Science and Engineering by the Human Genome and Stem Cell Research Centre (HUG-CELL) is based on tissue bioengineering techniques known as decellularisation and recellularisation.
The organs of some donors are sometimes damaged in traffic accidents, but these may soon be transplantable if the HUG-CELL team realises its goal.
The decellularisation and recellularisation approach involves taking an organ from a deceased donor and treating it with detergents and enzymes to remove all the cells from the tissue. What remains is the organ’s extracellular matrix, containing its original structure and shape.
This extracellular matrix is then seeded with cells from the transplant patient. The theoretical advantage of this method is that the body’s immune system won’t rile against the new organ as it already contains cells from the patient’s own body, thereby boosting the chance of long-term acceptance.
However, the problem with the decellularisation process is that it removes the very molecules that tell cells to form new blood vessels. This weakens cell adhesion to the extracellular matrix. To get around this, the researchers have introduced a stage between decellularisation and recellularisation. After decellularising rat livers, the scientists injected a solution that was rich in the proteins produced by lab-grown liver cells back into the extracellular matrix. These proteins then told the liver cells to multiply and form blood vessels.
These cells then grew for five weeks in an incubator that mimicked the conditions inside the human body. According to the researchers, the results showed significantly improved recellularisation.
“It’s comparable to transplanting a ‘reconditioned’ liver, said Mayana Zatz, HUG-CELL’s principal investigator and co-author of the article. “It won't be rejected because it uses the patient’s own cells, and there’s no need to administer immunosuppressants.”
Extracellular matrix of a decellularised liver | Image Credit: HUG-CELL/USP
Obviously, there is a yawning gap between proof of concept and the operating theatre, but the goal is to scale up the process to create human-sized livers, lungs, hearts, and skin for transplant patients.
“The plan is to produce human livers in the laboratory to scale,” said lead author Luiz Carlos de Caires-Júnior to Agência FAPESP. “This will avoid having to wait a long time for a compatible donor and reduce the risk of rejection of the transplanted organ."
This technique could also be used to repair livers given by organ donors that are considered borderline or non-transplantable. “Many organs available for transplantation can’t actually be used because the donor has died in a traffic accident,” Caires-Júnior added. “The technique can be used to repair them, depending on their status.”
Even if we are at the early stages of this approach, it bodes well for future research. And for those on the organ transplant list, a reconditioned liver would be as good as a new one – complete with their very own factory settings.
Read the paper here: https://www.sciencedirect.com/science/article/abs/pii/S0928493120337814
Using 2D imaging techniques to diagnose problems with the heart can be challenging due to the constant movement of the cardiac system. Currently, when a patient undergoes a cardiac MRI scan they have to hold their breath while the scan takes snapshots in time with their heartbeat.
Still images are difficult to obtain with this traditional technique as a beating heart and blood flow can blur the picture. This method becomes trickier if the individual has existing breathing problems or an irregular heartbeat.
These problems can lead to trouble in acquiring accurate diagnostics.
Now, a team based at the Cedars-Sinai Medical Center in California, US, have detailed a new technique – MR Multitasking – that can resolve these issues by improving patient comfort and shortening testing time.
‘It is challenging to obtain good cardiac magnetic resonance images because the heart is beating incessantly, and the patient is breathing, so the motion makes the test vulnerable to errors,’ said Shlomo Melmed, Dean of the Cedars-Sinai Center faculty.
An MRI Scanner. Image: Wikimedia Commons
‘By novel approaches to this longstanding problem, this research team has found a unique solution to improve cardiac care for patients around the world for years to come.’
By developing what the team consider a six-dimensional imaging technique, the Center has embraced the motion of a heartbeat by capturing image data continuously – creating a product similar to a video.
‘MR Multitasking continuously acquires image data and then, when the test is completed, the program separates out the overlapping sources of motion and other changes into multiple time dimensions,’ said Anthony Christodoulou, first author and PhD researcher at the Center’s Biomedical Imaging Research Institute.
‘If a picture is 2D, then a video is 3D because it adds the passage of time,’ said Christodoulou. ‘Our videos are 6D because we can play them back four different ways: We can playback cardiac motion, respiratory motion, and two different tissue processes that reveal cardiac health.’
Your guide to a cardiac MRI. Video: British Heart Foundation
Testing ten healthy volunteers and ten cardiac patients, the team said the group found that the method was more comfortable for patients and took just 90 seconds – significantly quicker than the conventional MRI scan used in hospitals. For each of the participants, the scan produced accurate results.
The team are now looking to extend its work into MR Multitasking by focusing on other disease areas, such as cancer.
Stem cells with shared genetic information aid in the study of human disease. Image: Kyoto University/Knut WoltjenSingle nucleotide polymorphisms (SNPs) are the most common form of genetic mutation, with more than ten million currently identified, and are often found in hereditary diseases – from Alzheimer’s to diabetes.
Due to the precise nature of SNPs, researchers need to compare genetic differences with isogenic twins – two cells which differ in their makeup by only a single gene.
To do this, scientists in Japan have used induced pluripotent stem (iPS) cells to create a novel gene editing technique that can modify DNA to a single gene.
iPS cells are unique in that they retain the genetic makeup of a donor and can be converted into any cell type. These characteristics mean the cells are perfect for testing new treatments in a laboratory setting.
The team – led by Dr Knut Woltjen and based at the Centre for iPS cell Research and Application at Kyoto University, Japan – use the method to insert an SNP modification along with a fluorescent report gene as a marker for the modified cells.
As adding the reporter gene is another modification to the genome, the researchers created a duplicated DNA sequence that flanks the gene in order to remove it.
These strands hang over the sequence of the reporter gene so that once the latter is removed, the two resulting strands can join together – a method known as microhomology-mediated end joining.
In the Alzheimer’s affected brain, abnormal levels of the beta-amyloid protein clump together to form plaques (seen in brown) that collect between neurons and disrupt cell function. Image:NIH Image Gallery
Unique target sites were also added to remove the gene using the enzyme CRISPR, which cuts DNA. As a result, only the modified SNP is left in the genome of the cell.
One of the isogenic twins receives the mutant SNP and the other receives the normal SNP, allowing for a comparison to be made.
Dr Woltjen calls the new technique Microhology-Assisted eXcision, or MhAX. ‘To make MhAX work, we duplicate DNA sequences which are already present in the genome. We then let the cell resolve this duplication. At the same time, the cells decide which SNPs will remain after repair,’ said Woltjen. ‘One experiment results in the full spectrum of possible SNP genotypes.’
The team have already collaborated with other Japanese universities on the application of their novel method, using the HPRT gene – a mutation that can lead to gout – as the first example of its potential use in therapy.
Their work shows that cells with the HPRT mutant SNP had similar issues with metabolism associated with gout patients, while the isogenic control cells had no problems.
Following on from this success, Woltjen and his team are now applying the technique to different diseases associated with SNPs, including diabetes.