An international team of researchers has published study results recently demonstrating that Multipotent Adult Progenitor Cells (MAPCTM) increase the long-term survival of organ transplants in instances when the cell donor is not related to the patient or the organ donor, and also appear to alleviate the need for long-term immune suppression. The preclinical research, conducted using a standard heart transplant model, also demonstrated that the transplanted organ retained its immunologically privileged state during a subsequent transplantation procedure into a naïve recipient, illustrating the durability of the effect. The risk of rejection and the requirement for long-term immunosuppression are key challenges in donor organ transplantations, which could be addressed by administering the clinical MAPC product, MultiStem®, to transplant patients.
Athersys and the team at Regensburg have moved quickly to advance these findings into a clinical setting by obtaining authorization to conduct a clinical trial in liver transplant patients. Athersys has established several clinical programs in the inflammatory and immune area, including a completed Phase 1 study in the U.S. in hematopoietic transplant support, and is working in collaboration with Pfizer Inc. to complete an ongoing Phase 2 clinical trial in Inflammatory Bowel Disease. Athersys also has clinical programs in other areas, including an ongoing Phase 2 clinical trial to treat ischemic stroke patients.
"The immunological attributes of MAPCs make them a promising candidate for providing immunomodulatory support after organ transplantation," explained Marc Dahlke, M.D., Ph.D., a lead investigator in the study. "In contrast to other cell types, MAPCs can be expanded in a manner that makes them amenable to large scale production, potentially making them an optimal choice for routine clinical use — especially in the so-called 'third party' scenario in which the cell donor is unrelated to the organ donor and recipient."
Most other cell therapy trials have used cells of either the organ donor or recipient. However, the preparation of such customized cell therapies is costly and challenging, since it must be done one patient at a time, and can lead to inconsistent results. With this in mind, the Dahlke team decided to explore the potential of a third-party-derived MAPC to act as a universal donor. This is the approach being taken clinically by Athersys in several other disease areas. They conducted their study on rats that received allogeneic heart grafts. One group of animals was treated after the transplantation with a combination of MAPCs and short-term administration of low-dose immunosuppressive drug. Another group was administered immunosuppressive drugs only, while a third group received no extra treatment at all. Only grafts from those animals receiving MAPC and short-term immunosuppressive therapy survived long term.
When long-term accepted heart grafts were recovered from the MAPC-treated animals and re-transplanted into yet another group of untreated animals (genetically identical to the first group of recipients), they engrafted successfully, without triggering rejection, even when no immune suppressive drug was administered. This finding demonstrates that an immunoprivileged state, or "regional immune tolerance," had been induced in the graft that can be carried into another untreated animal.
"In the group with no treatment, the grafts were rejected in less than 2 weeks; short-term immunosuppressive drug treatments kept them intact just a few days longer. However, rats given a combination of short-term immunosuppressive treatment and MAPCs exhibited a high percentage of prolonged survival, even after treatment with immune suppressive drugs was stopped, indicating a promising pathway for clinical immunotherapy," Dr. Dahlke commented. "If transplantation procedures could be conducted with lower requirements for immunosuppressive drugs, this could provide a substantial benefit to patients, and could also broaden the impact of transplantation medicine, helping many more patients and providing a better quality of life."
The research effort was led by a team of renowned transplant specialists at the University Hospital in Regensburg, Germany, working in collaboration with scientists from Athersys and the U.S. National Center for Regenerative Medicine, located in Ohio. Other members of the team included scientists from Erasmus University Medical Center in Rotterdam and Case Western Reserve University in Cleveland.
"This pioneering work demonstrates that MultiStem may have broad relevance in the field of clinical transplantation by addressing several of the major hurdles that represent real challenges for patients," said Dr. Gil Van Bokkelen, Chairman and CEO at Athersys. "We're excited by this research, because it supports the broader relevance of MultiStem in the treatment of inflammatory and immune conditions, such as our ongoing Phase 2 clinical trial with Pfizer in Inflammatory Bowel Disease. We think MultiStem could have a significant impact in transplantation medicine, as well as related areas, and are excited about the initiation of the clinical trial at Regensburg in liver transplant patients."
Illustration: Microsoft clipart.
Athersys Inc. News Release (07/09/13)
Abstract (Stem Cells Translational Medicine; (07/08/13))