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Cleveland-based Athersys, Inc. is developing stem cell therapies that may free transplant patients from the lifelong use of immunosuppressant drugs, which can cause side effects including infection, kidney failure and cancer.

(Marvin Fong, The Plain Dealer)

CLEVELAND, Ohio -- One of the biggest problems facing anyone who receives an organ transplant is rejection. When the immune system, which is designed to keep us healthy, reacts to a donated organ as if it were a foreign invader and attacks, doctors have to prescribe powerful drugs to keep it in check.

Those drugs, called immunosuppressants, are a necessary evil for most transplant recipients for as long as they live. They prevent rejection, but can lead to infection, gastrointestinal disease, pancreatitis, cancer and kidney failure.

For decades transplant specialists have been searching for ways cut down on these side effects, or, better yet — eliminate the need for the drugs at all.

Now, early work in rats performed by researchers from Cleveland-based Athersys, Inc. has suggested that a stem cell product the biopharmaceutical company is developing may accomplish that second goal.

“If what we’ve seen in animals works the same way in humans we really open up the door for a change in the way that people think about transplantation and the need for these lifelong immunsuppressive drugs,” said B.J. Lehmann, Athersys president and chief operating officer. “That’s a pretty big deal for the transplant community.”

The company is developing a product called MultiStem, which is made from adult stem cells harvested from healthy volunteers that are then multiplied by a proprietary technique. MultiStem is also being tested to see if the cells can help heal the damage caused by heart attacks and stroke, and to reduce inflammation in conditions such as graft-versus-host disease and inflammatory bowel disease.

Because the MultiStem stem cells are developed from a third party — that is, neither the donor nor the recipient — they have the advantage of being available at any time for any transplant. The cells also can be frozen and stored for later use.

In the recent study, published earlier this month in the journal STEM CELLS Translational Medicine, researchers from Athersys and Regensburg University Medical Center in Regensburg, Germany, used the same type of stem cells, called MAPCs (multipotent adult progenitor cells), only taken from rats.

They found that giving rats who received a heart transplant a dose of MAPCs improved the odds that the donated heart would be "tolerized," meaning that the recipient's immune system would accept the organ as non-foreign.

"The immune system sees the donor organ as their own, their own 'self' organ, so they don't reject it," said Dr. Kareem Abu-Elmagd, director of the transplantation center at the Cleveland Clinic, who was not involved with the research.

Part of the reason for the acceptance could be activation of immune cells in the donor heart and in the recipient called T-regulatory cells, which modulate or suppress the immune system.

“For some reason when you give these [MAPCs] it stimulates the immune system of both the recipient and the donor organ to have more of these T-regulatory cells,” Abu-Elmagd said. “So it acts as if it’s a drug that suppresses the immune system and makes the acceptance rate very high with minimal to no immunosuppressive drugs.”

To prove this, researchers took the donated heart out of the recipient rats and transplanted it a second time into a different rat. The donated heart was accepted without any immunosuppression at all, meaning the organ itself had been affected by the initial MAPC treatment.

“It implies that the stem cell therapy has affected the organ, making it less apt for rejection,” Lehmann said.

Athersys is confident enough in the preliminary results that it recently started a small-scale clinical trial in human liver transplant patients in Germany using the MultiStem treatment. The trial will enroll between 12 and 20 patients and may be complete by the end of 2015.

Abu-Elmagd said the results from the initial animal trial are encouraging, but “of course there are unanswered questions.”

“One, humans may behave totally differently from animals,” he said. “Two, it may be better to have stem cells from the donor rather than the third party. My expectation is that stem cells from the same donor would work better.”

Some trials using stem cells from both the donor and the recipient have shown positive results. A small trial of kidney transplant patients published in Science Translational Medicine last year showed success in limiting or eliminating immunosuppression a year after the transplant when patients received stem cells from their donor.



A larger trial published in the Journal of the American Medical Association last year demonstrated that kidney transplant patients who received their own bone-marrow derived stem cells had a lower risk of acute rejection, opportunistic infection and better estimated renal function at one year.

Still, taking stem cells from a donor or recipient isn’t always possible, for health reasons, or if the donor is deceased. It also takes time to isolate the stem cells and grow enough to use for treatment.

Abu-Elmagd is interested in participating in a clinical trial in the United States if the Phase 1 trial in Germany is successful.

“I’ll be the first to jump on it,” he said.