To save patients with a severe form of type 1 diabetes, pancreatic cell transplantation is the last resort. However, the transplant process is long and complex: a significant part of the grafted cells die quickly without being able to engraft. By adding amniotic epithelial cells to these cell clusters, researchers have succeeded in creating much more robust ‘super-grafts’ of islet of Langerhans. Once transplanted, more of them engraft; they then start producing insulin much more rapidly.
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Transplantation often takes several donors to treat one person, whereas we are in desperate need of donors. The Solution may reside in Super-graft.
According to the WHO report, the number of people with diabetes is rising. It has risen from 108 million in 1980 to 422 million in 2014. So it is important to visualise the risk public is facing out of diabetes. Diabetes occurs either when the pancreas does not produce enough insulin or when the body cannot effectively use the insulin it produces. In this article, we will understand how scientist developed ‘super- graft’ to challenge diabetes.
In type 1 diabetes the immune system destroys pancreatic cells called as beta cells. When beta cells are damaged, they become incapable of making insulin and the process go off track. Insulin is a key hormone with which the sugar or glucose move into your body’ s tissue, which later is utilised as fuels.
Glucose is produced by the cluster of cells in the pancreas called islet of Langerhans cells. And sometimes the patient with type 1 diabetes lastly resort to pancreatic cell transplantation.
Let us see what happens in the pancreatic cell transplantation.
Pancreatic cell transplantation without super-graft
It is an experimental treatment for type-1 diabetic patients. In this type of surgery, doctors isolate islets from the pancreas of a healthy organ donor. Doctors then inject the healthy islet cells taken from the donor into a vein that carries blood to the liver of a person with type 1 diabetes. These islets begin to make and release insulin in to the recipient’s body.
According to Ekaterine Berishvili, a researcher in the Department of Surgery at UNIGE Faculty of Medicine this process is well controlled. And about fifteen patients benefit from it every year in Switzerland.
However, this transplant procedure is time-consuming and long with complications. Meanwhile, during transplantation, a significant part of the grafted cells die quickly without being able to engraft. Key factors responsible for early graft loss are inflammation at the site of implantation and impaired revascularization.
Blood supply to pancreatic islets is disrupted during transplantation which is inevitable. Hence in the first weeks of transplantation, oxygen and nutrients are delivered to avascular islets exclusively by diffusion until they become revascularized.
Super-graft might help
Recently scientists from the University of Geneva (UNIGE) and the Geneva University Hospitals (HUG), Switzerland, have come up with the solution. The solution lies in creating more super robust islets of Langerhans. And it was achieved by adding amniotic epithelial cells to these cell clusters.
So what are amniotic epithelial cells?
An amniotic epithelial cell is a form of stem cell extracted from the lining of the inner membrane of the placenta. Amniotic epithelial cells start to develop around 8 days post-fertilization.
Over the last decades, human amniotic epithelial cells (hAECs) have gained interest in regenerative medicine due to their high proliferative capacity, multilineage differentiation, ease of access, and safety.
Amniotic epithelial cells isolated from human amnion (hAECs), are mostly desired and posses competitive characteristics that make them stand out between other stem cells. The remarkable ability of hAECs is to get differentiate toward all three germ layers, they are not tumorigenic and they have immunosuppressive properties.
These cells secrete considerable amounts of proangiogenic and anti-inflammatory growth factors. Hence due to their growth factor secretion profile and antifibrotic properties make hAECs attractive cells for a construct designed to enhance the engraftment and vascularization of islet cells.
Steps involved in super-graft to treat diabetes
The experiment included both in-vitro as well as in-vivo conditions. In in-vitro, when the amniotic epithelial cells were added the cell clusters formed a regular sphere. This indicated better intracellular communication and connectivity.
Whereas in case of in-vivo conditions the researchers transplanted their “super-islets” of Langerhans into diabetic mice, that quickly began to produce insulin.
According to Fanny Lebreton, a scientist at the Department of Surgery at UNIGE Faculty of Medicine and the first author of this work noted though the cell clusters were very few, even then the super islets adapted very well to their new environment and vascularized quickly.
We know that a good vascularization is important and critical. It aids in supply of oxygen and nutrients to the new organ and guarantees their survival. Also the experiment showed, the artificial islets quickly began to produce insulin.
“Amniotic epithelial cells have the unique characteristic of protecting the fetus, which is also a “non-self,” from attacks by its mother’s immune system. We believe that the same mechanism is at work to protect the grafts. The protective mechanism, observed here on cell transplants, could also take place in other types of transplants or even in xenotransplantation – where non-human cells or organs are transplanted into humans.”
– Ekaterine Berishvili
This work was supported by the Swiss National Science Foundation, the Fondation Privée des HUG, the Fondation Romande de Recherche sur le Diabète and the European Foundation for the Study of Diabetes, as well as by the Juvenile Diabetes Research Foundation.
These discoveries now need to be confirmed on human subjects. Since the use of amniotic epithelial cells is already common in other clinical settings without adverse side effects, this could be done relatively quickly. An important hope for all those awaiting a transplant.
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