Biman Mandal (left) and Manishekhar Kumar coated the scaffold, which contains the beta cells, with a semi-permeable membrane barrier to prevent the immune cells from crossing the membrane and killing the beta cells.
The beta cells in the scaffold were able to produce adequate amount of insulin in response to different glucose levels within a few seconds.
Researchers at the Indian Institute of Technology (IIT) Guwahati have successfully created an implantable bioartificial pancreas model grown within a 3D silk scaffold. The “pancreas”, which encapsulates the insulin-producing beta cells, is capable of naturally producing insulin in a sustained manner. If successful in animal and human trials, it can be used for treating people with Type 1 diabetes.
In Type 1 diabetes, the pancreas produces little or no insulin. Insulin is a hormone needed to allow sugar (glucose) to enter cells to produce energy. The results were published in the journal ACS Biomaterials Science & Engineering.
The silk scaffold (6 mm in diameter and 2 mm in thickness) was made porous by using salt grains of specific size to dissolve the silk proteins. The pores — 400-500 micrometre in size — allowed glucose and oxygen to enter the scaffold and insulin released by the beta cells to enter the bloodstream; there was also greater cell survival. Insulin producing beta cells taken from 8- to 10-week-old rats were added to the scaffold.
Type 1 diabetes is an autoimmune disease and arises when the body’s immune system kills the insulin-producing beta cells. So the team led by Prof. Biman Mandal from the Department of Biosciences and Bioengineering at IIT Guwahati coated the scaffold, which contains the beta cells, with a semi-permeable membrane barrier. The membrane allows insulin produced to be released into the blood stream but does not allow the immune cells to cross the membrane and kill the beta cells. The membrane can last for a long time.
To ensure that the implant is not rejected by the body’s immune system, drugs that suppress the immune system were embedded in the scaffold. “We implanted the membrane-bound scaffold into mice for four weeks and checked for immunocompatibility and barrier function. The scaffold was found to be biocompatible with had adequate barrier functions,” says Prof. Mandal, who is the corresponding author of the paper. Because the scaffold was biocompatible it did not trigger any immune reaction or cause any adverse reaction when implanted.
The drugs suppress the immune system only locally and hence different from whole-body immunosuppression when drugs are taken orally, like those who have undergone organ transplantation.
Studies carried in the lab showed that the beta cells in the scaffold were able to produce adequate amount of insulin in response to different glucose levels within a few seconds.
“We expect the islets cells to function for three-four months as the cells regenerate and continuously produce insulin. Even if the cells don’t regenerate and die out we can inject fresh beta cells into the implanted capsule so that the production of insulin is continued,” says Prof. Mandal.
Since Type 1 diabetes patients do not have insulin-producing beta cells, the researchers have turned to stem cells to produce beta cells. “We have already used stem cells that have differentiated [become specialised cells] into beta-like cells producing insulin,” says Manishekhar Kumar from the Department of Biosciences and Bioengineering at IIT Guwahati and the first author of the paper.
The researchers are planning to carry out trials in animals. “We have already produced diabetic rats and would soon implant the scaffold in these rats to reverse diabetes,” says Prof. Mandal. “In humans the scaffold can be implanted in the fat layer (omental patch) present in the belly area.” It will be some time before it can be tested in humans.
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