Organ transplantation: Using biomaterials to prevent immune rejection

Author: Guest, 01/26/16

Samantha is a PhD student in the Chemical Engineering and Applied Chemistry department at the University of Toronto. She has previously investigated regeneration in a non-mammalian gecko model during an MSc program, and now currently combines stem cell biology and biomaterials to encapsulate and deliver therapeutic cells to the stroke-injured brain. Samantha became interested in scientific communication as a means to combine her love of writing and science to share exciting scientific topics and discoveries to a broader community.

Canada recently added another scientific accomplishment to its impressive list as the first hand transplant in Canada was successfully performed at Toronto Western Hospital. Organ transplantation has long been thought impossible due to the response mounted by the donor’s immune system, which rejects the transplant. Organ rejection is mediated by the adaptive immune system, specifically by T lymphocytes (T cells), which become activated when they encounter non-self molecules (known as antigens).

The realization that donor and recipient tissue must be matched, combined with other advances in medicine, has allowed surgeons to perform successful whole organ transplants; however, to prevent graft rejection, patients must take immunosuppressive drugs for the rest of their lives, and even so up to 61% of grafts will not survive longer than 10 years. Current immunosuppressive drugs suffer from being too broadly-acting and chronically toxic, meaning that taking these agents for years often leads to serious side effects, such as damage to the transplant, life-threatening infections and even certain cancers. It is extremely challenging to target the specific part of the immune system involved in graft rejection, while still allowing the rest of the immune system to provide its normal protection.

Researchers are turning to biomaterials to manipulate the behaviour of T cells, thereby creating a more efficient way to prevent transplant rejection. Nanoparticles (nanoscale spheroids made of a biocompatible polymer), delivered into the body, can be used to prevent an immune response by specifically targeting only the desired immune cells. Researchers consider them very versatile because their surface can be chemically modified to carry and present different antigens to the cells of the body. Modifying nanoparticles with a tolerance-inducing antigen, and then injecting them into the recipient, can target patrolling immune cells without affecting other cells. This was recently demonstrated by injecting one dose of peptide-coated nanoparticles into mice that had received a bone marrow transplant. This strategy reduces side effects by providing more precise targeting, which preserves function of the remainder of the immune system and removes the need to inject toxic drugs systemically.

Another exciting recent use of biomaterials for immune modulation involves the use of ‘immunocamouflage.’ Because T cells rely on cell-to-cell interactions to identify threats, we can cloak donor cells in a polymer that T cells do not respond to and deliver them into the recipient. Canadian researchers, at the University of British Colombia, have demonstrated this by coating cell membranes in methoxypoly (ethylene glycol) (mPEG). The chemical structure of mPEG makes it difficult for cells to recognize and attach to, rendering the coated cells virtually undetectable by immune cells. Surprisingly, in addition to masking the presence of the injected cells, this strategy has been shown to also induce a tolerance in the entire immune system, preventing T cells from becoming activated when challenged with donor tissue. This strategy is especially attractive because it can completely avoid immune cell activation, rather than merely suppressing it.

Although working with the immune system is extremely challenging, given the complexity and unique makeup of each person’s immune profile, biomaterials have the potential to provide a more efficient and safe method of immune suppression for organ recipients. With continued optimization of the structural properties of the biomaterial, we may one day see these exciting new techniques emerging for clinical use.

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Signals Blog accepts guest blog posts on topics relevant to stem cells and regenerative medicine, as well as submissions for its Right Turn Friday feature. See http://www.signalsblog.ca/about/ for more information.
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