What We Have Covered in This Article
Last Updated on April 14, 2021 by Editor Futurescope
Many patients with liver disease have been facing difficulties when they needed a liver transplant. They had to wait for long periods to get a compatible liver donor. Also if a donor got involved in an accident and their liver got damaged it could not be repaired.
The good news is that a technique to reconstruct and produce livers in the laboratory has been developed by researchers at the Human Genome and Stem Cell Research Centre (HUG-CELL).
The research was done using rat livers and the plan is to use the same technique used to produce rat Iivers to produce human livers in the next stage of the research. There is a need for an increased supply of transplantable human livers. This technique would be a lot helpful to patients in need of liver transplants.
Advantages of the technique
Since the technique to producing transplantable livers in the laboratory solves many of the problems which many patients with liver disease face, it is a very advantageous technique.
The advantages include that the technique enables up to scale production of livers in the laboratory, lowers the risk of liver rejection by the patient’s body and damaged livers can be repaired. We look at these advantages in detail below.
- The technique allows up to scale production of livers
The technique to reconstruct and produce livers in the laboratory is probably the way out of the shortage of transplantable human livers. The main reason why this technique was developed is to produce enough livers in the laboratory to cater to those needing liver transplants.
Enough transplantable human livers mean patients won’t have to wait for long periods for a donor who is compatible to come through for a donation. According to the plan, livers will be readily available for those needing a transplant.
- With the technique, livers produced in the laboratory will be made of the patient’s cells
Many liver patients who get liver transplants often face problems like immune system reactions and incompatibility issues. As a result, such patients will have to spend their lifetime taking immunosuppressant’s to combat the issue.
The good news is that this technique will minimize the risk of rejection of the liver by the patient’s body when it’s transplanted. This is because the liver will be comprised of the liver recipient’s cells which will make it highly compatible.
- With the technique, borderline and non-transplantable livers can be reconstructed
There has been a liver transplant crisis because borderline and non-transplantable livers couldn’t be repaired. However, with the technique, borderline as well as non-transplantable livers can be reconstructed.
This means that even if a donor gets involved in an accident, and their liver gets damaged, it can be repaired using this technique. This will ensure that there is an increased supply of transplantable livers.
- The technique means there won’t be a need to administer immunosuppressants to liver transplant recipients
Because liver transplant recipients often faced immune system reactions there was a need to give them immunosuppressant medication to tackle the problem. However, with this technique that scientists developed when the patient gets the liver transplant, there will be no need to administer immunosuppressant medication.
This is because the liver to be transplanted will be made of the patient’s own cells. This ensures that there won’t be problems with the transplanted liver in the long run.
How does the technique work?
The technique to produce transplantable livers in the laboratory involves the processes of decellularization and recellularization. It’s based on tissue bioengineering methodologies developed a few years ago to produce transplantable organs.
Below we look at how the technique to produce transplantable livers in the laboratory works, so read on.
- The technique involves the decellularization Process
Decellularization can be defined as the process whereby bioengineering techniques are used to isolate the extracellular matrix of an organ from its surrounding cells. The extracellular matrix containing the original tissue will remain which is then used in tissue regeneration.
In this technique, a liver from a deceased donor is treated to get rid of cells from the liver tissues. Different solutions compromising detergents or enzymes are used to get rid of the cells from the tissue.
The removal of the cells from the tissue will ensure that the extracellular matrix will remain. This remaining extracellular matrix will be comprised of the original structure and the shape of the tissue.
- The technique involves a process of enriching the extracellular matrix
The technique also involves enriching the extracellular matrix with a solution of essential molecules like SPARC. Also, proteins produced by liver cells are also used to enrich the extracellular matrix. Without this procedure, recellularization will be compromised as the adhesion of cells to the matrix will be weakened.
Also, when the process of enriching the extracellular matrix is not done, cells won’t be able to multiply as they should in order to form blood vessels. In other words, enriching the extracellular matrix will make the produced liver healthy.
- Recellularization Process
Recellularization is the next step after enriching the extracellular matrix. Recellularization is the process whereby cells are seeded to the extracellular matrix to produce a practical organ, in this case, liver.
In this step, cells from the liver transplant recipient are seeded into the extracellular matrix. This will ensure that in the long term there will be no immune system issues because of the transplanted liver.
According to Mayana Zats, HUG-CELL’s principal investigator, the liver made in the laboratory will not be rejected because it uses the patient’s cells, and there’s no need to administer immune suppressants.
A look at the study on rat liver
Now let’s look at the study which was done on rat liver. The rat liver underwent a series of processes which include liver isolation and decellularization, extracellular matrix enrichment, the addition of essential liver cells, and growing the liver in an incubator. Below we look at the steps which were taken during the study.
First step: Rat liver isolation and decellularization
Rat livers were isolated and decellularized. The process of decellularization during the study involved isolating the extracellular matrix of the rat liver from its surrounding cells. The extracellular matrix would then be used for tissue regeneration.
Note: This step is important as it enables the creation of a transplantable liver that will not be rejected by the antibodies of the transplant recipient.
Second step: Enriching the extracellular matrix
After the decellularization of the rat liver, a solution of essential molecules like SPARC was injected into the extracellular matrix. Essential proteins which make the liver healthy were also injected into the extracellular matrix.
The proteins also facilitate liver cells multiplication and production of blood vessels. These proteins were made by liver cells which were grown in the lab.
Third step: Recellularization (Addition of hepatocytes, endothelial cells, and mesenchymal cells)
After enriching the extracellular matrices with the solution, hepatocytes, endothelial cells as well as mesenchymal cells were added. Rat liver extracellular matrices were treated with the solution, and hepatocytes, endothelial cells, and mesenchymal cells were introduced into the material.
The mesenchymal cells which were used for the process of recellularization were taken from human induced pluripotent stem cells. The human-induced pluripotent stem cells were made from deprogramming skin cells of an adult to form sort of an embryonic pluripotent state. Liver cells were injected into the extracellular matrix using a syringe pump
Note: Recellularisation was done to produce a Iiver with characteristics like those of a human.
Fourth step: The liver was grown in an incubator for five weeks
After the process of recellularization, the liver was then allowed to grow for a period of five weeks in an incubator under conditions like those in the human body. Five weeks is the time needed for the liver to grow fully?
This process of growing the liver in an incubator shows that growing organs in the laboratory has become a reality.
What can be derived from the study?
From the study, it was seen that human stem cell differentiation can be induced in cell lineages which are components of the liver to remake the liver so that it works well as a normal liver.
From the study, it was also seen that enriching the extracellular matrix made the process of recellularization a lot better. Treating the matrix also encouraged liver cell growth. It also improved the overall functionality of the organ.
The other discovery made when the study was done is that other organs like lungs can also be produced using the same technique.
In Conclusion
For a long time, there has been a liver transplant crisis. Patients in need of a liver transplant had to wait for long periods until a compatible liver donor was found. Also, patients faced many other problems discussed in this article earlier.
The good news is that scientists at the Human Genome and Stem Cell Research Centre (HUG-CELL) have made a great development as they discovered a way to reconstruct and make transplantable livers in the laboratory.
This is indeed a major breakthrough as the technique will surely eliminate issues the were being faced by patients needing liver transplants.
