Today I am going to talk about an article published in AJP – Endocrinology and Metabolism in 2008. Name of the article is “Subcutaneous transplantation of embryonic pancreas for correction of type 1 diabetes”. You can see the article from this link here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2645017/
Type 1 Diabetes Mellitus (DM) is a disease caused by destruction of the insulin producing β cells of the pancreas islets by the owner’s immune system. This is an autoimmune disease and its conventional treatment is repeated insulin injections all lifelong.
There are two current surgical treatment processes, one of which is pancreas transplantation which is really hard to accomplish and full of post-transplantation complications. Also the lack of donors, the problems caused by the immune-suppression and poor graft survival are the disadvantages of this surgery. Because of these problems, pancreas transplantation is only used in nephropathy occurred type 1 DM patients with kidney transplantation.
The other way is transplantation of pancreatic islets through the portal vein into the liver. This way also has some complications caused by the method, like portal hemorrhage, portal hypertension and thrombosis.
Because of this restrictive current situation in DM treatment, researchers from Vanderbilt University School of Medicine thought about a better surgical treatment strategy which causes minimal complications and needs the less immunosuppression.
In this study, researchers tried to transplant embryonic pancreases to nude, Type 1 DM mice and investigate the results like blood glucose, insulin, neoplasm, vascularisation of graft.
Firstly they created a type 1 DM model in nude mice. They used streptozotocin, which causes pancreas β cell destruction, thus plasma insulin levels decreases and blood glucose rises above 300 mg/dl.
They used pregnant mice, took their embryos out and reach the pancreatas. Transplantation of embryos have 3 different sides, underneath the renal capsule, under the skin of earlobe and dorsal surface of the body of nude mice. After 3-5 month, they euthanized the mice and took the pancreases for immunohistochemical studies.
As we talk about the results of the study, researchers find out that body mass of the mice increased significantly, which is a gross finding that shows mice were getting better.
In immunohistochemical studies they showed the differentiation and vascularisation of the graft is quite adequate. Also they didn’t find out any neoplastic differentiation.
It’s shown that plasma glucose levels are similar to normal non-diabetic mice although their insulin levels aren’t significantly different than untreated mice. Therefore they investigated their adiponectin levels and found out that transplanted mice have significantly high levels of adiponectin than normal and untreated type 1 DM mice. Adiponectin is a hormone-like substance released by fat tissue that has important role in glucose homeostasis. No study in literature showed that these mice (NCRNU nude mice or NOD-SC mice.) have low insulin levels (high insulin sensitivity) in glucose control. In fact researchers weren’t expecting the low insulin levels as a result, but because of that, they figured out the importance of adiponectin in blood glucose homeostasis.
After I read this article, some questions came in my mind. First of all, as we know, Type1 DM is an autoimmune disease causing by self-reaction of our immune cells to pancreatic beta cells. In this study they create a Type 1 DM model with use of streptozotocin to cause beta cell damage. Also they used nude mice, which don’t have immune system to fight with the graft. My professor told me that researchers usually use this way to create DM model in mice, but maybe we are in the wrong way to create DM models and depend on this method in researches. Maybe the result is the same; yes, we destroy the beta cells, lower plasma insulin and raise plasma glucose but not with same mechanism of Type 1 DM. In human it is a complete different disease with a major role of the immune system. We don’t know if human would reject the pancreas or wouldn’t reject however create autoimmunity to the new pancreas and have type1 DM in time again. Maybe we can create a real type 1 DM model in mice with immunotherapy educating the lymphocytes to destroy the β cells. Well, I know that sounds hard to do 🙂
Besides the technical questions of mine, we all know that using of human embryos to treat diseases will cause severe ethical problems. So, unfortunately this is a limitation to advance the treatment and use it in human therapy.
However, after all my negative comments, we see all- positive results in this study. Actually I like this article and I think it is the beginning of a new road to cure type 1 DM with stem cell.
I didn’t have time to take a look at the literature about further studies, but I am really curious about this subject and will come up with similar articles. There are some other articles that I obligated to read, so this issue will wait a while, but be sure that I will be back! Well… Till the next post, take care 🙂
Neslihan Turan 