Signals Blog

My guess…is an HSC (hematopoietic stem cell).

Because although these cells aren’t known for their civil disobedience, they do have a certain knack for making people more tolerant.

In fact, that’s why Dr. Megan Sykes, Director of the Columbia Center for Translational Immunology, finds them so interesting.  She wants to use these cells to teach a patient’s body to become tolerant to the cells of an organ donor. The objective: improving long-term graft acceptance and eliminating the need for chronic immunosuppression (which, for the record, is not fun).

Over the past two decades, Dr. Sykes and her collaborators at Harvard Medical School have tested regimens for combining bone marrow transplantation (bone marrow contains HSCs) with kidney transplantation in rodent and large animal studies.  She has also conducted some promising human clinical trials, which are reviewed in last month’s edition of Nature Immunology.

The basic idea is that by taking bone marrow from the organ donor and transplanting it into the recipient you form a mixed chimera, a state where the donor blood cells peacefully coexist with the blood cells of the patient. Although this state lasts only a few weeks, it can be sufficient to train the patient’s immune cells to be less militant toward donor antigens.

Of course, that’s quite a simplification. There are also steps to help the bone marrow engraft and to prevent Graft-versus-Host-Disease. As tricky and complex as this treatment sounds though, Dr. Sykes and her colleagues have been able to use it to take several kidney recipients off immunosuppressive drugs without subsequent graft rejection.

Now this is great news for the kidney field, but the reason I find toleration induction so fascinating is because it could revolutionize our capacities for allotransplantation at large.

For example, have you ever wondered why you don’t hear more about things like limb transplantations? There are thousands of accident victims that could benefit from such a procedure. While they are technically difficult, the main reason these procedures aren’t often done is because missing a limb is not a life-threatening condition. Thus, doctors find it ethically challenging to make a person suffer the consequences of chronic immunosuppression. If tolerance induction were mastered, however, then performing hand, foot, and even face transplantations (for trauma victims) may be more justifiable, providing a more “organic” treatment option than prosthetics and plastic fillers.

Beyond organ transplantation, tolerance induction could even help with cell therapies and tissue engineering. Take, for example, the recent advance in diabetes research, in which embryonic stem cells were used to make insulin producing beta-pancreatic cells. Promising? Yes. But one of the main obstacles is potential immune rejection. Since therapies made from allogeneic (non-patient, human) stem cells may offer greater versatility and faster availability than therapies made from a patient’s own cells (after all, you can only start making the latter after the patient has arrived at the clinic), overcoming the immune challenge via tolerance induction would be a significant accomplishment.

So what’s the bottom line? During development, our bodies are specifically taught to attack foreign cells. If HSCs can be used to preach a little tolerance, however, then we will be able to coexist with needed transplants in much greater harmony.

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Holly Wobma

Holly Wobma

MD/PhD student at Columbia University
Holly is an MD-PhD student at Columbia University in New York. She recently (2011) completed a Bachelor of Health Sciences Honours Degree from the University of Calgary, where she pursued research related to nanotechnology and regenerative medicine. In addition to research, she enjoys participating in science outreach roles. Previously, she contributed to an award-winning Nanoscience animation produced by the Science Alberta Foundation (“Do You Know What Nano Means?”), and served on the board of directors for the Canadian Institute for Photonic Innovations Student Network. Holly's lab tweets @GVNlab.