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Universal stem cell product could overcome key challenges in donor organ transplants

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In addition, the research demonstrates that the transplanted organ retained its immunologically privileged state during a subsequent transplantation into another naïve recipient.

The research, led by a team of transplant specialists at the University Hospital in Regensburg, Germany, developed the approach using a special class of stem cells referred to as multipotent adult progenitor cells (MAPCs). The MAPCs, collected from the bone marrow of a healthy donor, display a range of regenerative abilities and are already being used in clinical trials in several other areas, including for bone marrow transplant support, as well as for treating damage from stroke and heart disease and for certain autoimmune conditions. The study was conducted jointly with scientists at Erasmus University Medical Center, Rotterdam, and with a U.S.-based biotechnology company, Athersys Inc., in collaboration with scientists from the National Center for Regenerative Medicine based in Cleveland, Ohio.

“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 groundbreaking study that appears in the current issue of STEM CELLS Translational Medicine. “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 collected from either the organ donor or recipient. The preparation of such customized cell therapies is costly and challenging. With this in mind, the Dahlke team decided to explore the potential of a third-party-derived MAPC to act as a universal donor, consistent with the approach being taken clinically in several other disease areas. They conducted their study on rats that received allogeneic heart grafts.

One group of animals was treated after the transplant with a combination of MAPCs and a low-dose of an immunosuppressive drug administered for a short term. 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 immunosuppressives survived long-term.

When long-term accepted heart grafts were then 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. This held true even when no immune suppressive drug was administered.

The finding demonstrates that an immunoprivileged state 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 two 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 MAPC exhibited a high percentage of prolonged survival, even after treatment with immunosuppressive drugs was stopped. This indicates 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.”

“This is an interesting study demonstrating the potential of multipotent adult progenitor cells to serve as a universal cell product,” said Anthony Atala, MD, Editor of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine. “Being able to reduce the level of immunosuppressant drugs post-transplant would have significant benefits to patients.”

The study team is now recruiting for a Phase I clinical trial to assess the safety profile of MAPC infusion in liver transplant recipients. Athersys is also conducting clinical trials in several other areas using MultiStem®, the clinical grade product being developed that utilizes the MAPC technology. The company also has a partnership with Pfizer to treat inflammatory bowel disease, which is the subject of an ongoing international Phase 2 clinical trial, and also has an ongoing Phase 2 clinical trial for treating patients that have suffered an ischemic stroke.

 


 

Dr. Abu-Elmagd shares his view on the impact of using third party stem cells and transplantations:

Kareem Abu-Elmagd, MD, PhD — Director, Transplantation Center, Cleveland Clinic