A handy development

Allograft Dr PK Vemula with an injectable hydrogel loaded with immunosuppressants

Hand transplantation is unusual, with the most important factor being the availability of a donor. Globally, only 110 cases have been reported, limited to the US, Europe, China and Australia. The first transplant was done in France 13 years ago. The first Indian hand transplant was done on 12 January 2015 at the Amrita Institute of Medical Sciences, Kochi. A 30-year-old man, who had lost his hands in a train accident, was the recipient, with the donor being a 24-year-old road accident victim, who was declared brain dead. A team of 20 doctors took about 16 hours to conduct the operation.

Dr Subramania Iyer, professor and head of the plastic surgery department, says, “Each hand required connecting two bones, two arteries, four veins and about 14 tendons. Immunosuppressant drugs were administered before the surgery. There was careful monitoring of the blood supply to the hands and precautions to prevent infections were instituted while nursing.”

He adds, “About 14 days after the surgery, both hands were accepted by the recipient and he started regaining movement. Sensations will return gradually in three or four months. His immunosuppressant drugs will be continued indefinitely but reduced after three months.” The details of the transplant were added to the International Registry of Hand Transplants, which maintains stringent standards in the follow-up of these cases.

“This transplant has put the Indian scientific community in the league of developed nations insofar as composite tissue allotransplant is concerned,” says Dr Iyer.

After allograft transplantation— that of the hand, arm or leg — the standard procedure is to immediately administer immunosuppressant drugs for prevention of rejection by the immune system. However, toxicities and side-effects are associated with it since suppression of immunity leads to vulnerability to infection. Additionally, large doses of immunosuppressants damage other organs such as the kidney, liver and heart.

Using hydrogel (a biomaterial), a research collaboration by the Institute for Stem Cell Biology and Regenerative Medicine (inStem), Bengaluru, the University Hospital of Bern and the Brigham and Women’s Hospital (BWH) in the US developed a method of local delivery of immunosuppressant drugs targeting controlled release of medication, as per requirement. It helped in “reducing toxicity and markedly improving therapeutic outcomes leading to a paradigm shift in clinical immunosuppressive therapy in transplant surgery,” says Jeff Karp, PhD, Division of Biomedical Engineering, BWH Department of Medicine, a leading member of the team.

PK Vemula, PhD, Principal Investigator at inStem and a leading team member, says that this could significantly “extend the lifetime of the transplanted graft.”

Dr Vemula says, “Until now, delivering drugs for the treatment of autoimmune/inflammatory diseases was challenging due to unpredictable disease severity. Thus, traditional drug delivery systems failed. Hence, our vision is developing an approach where release of drugs is in response to disease-severity.” The study was published last year in the Science Translational Medicine.

The researchers developed a hydrogel with the immunosuppressant drug Tacrolimus. The hydrogel-drug combination was injected hypodermically after transplantation in a rat. The hydrogel remained inactive until it detected an immune response from the transplant, at which point it delivered the drug for months within the transplanted graft.

In pre-clinical studies conducted by the researchers, a local injection of the hydrogel-drug combo prevented rejection for more than 100 days, compared to those without it.

Dr Vemula has found encouraging results after testing this technology in a pig limb transplantation, in an unpublished study.

He hopes that human clinical trials of the system would be fast-tracked because both Tacrolimus and triglycerol monostearate (a molecule used for the gel) are FDA approved agents.

“My lab at inStem focusses on developing technologies/materials that could solve unmet clinical needs. Presently, we are establishing collaborations with Christian Medical College, Vellore, and the Centre for Stem Cell Research, Vellore,” he adds.



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