Stem cells in Transverse Myelitis – Are we ready?

We all hear about stories, studies and trials all over the world that sound promising, even miraculous when it comes to the use of stem cells to recover function.  What does this mean for diseases like transverse myelitis?  Why don’t we have a study in our patient population?  What does the future look like?

A major concern with using currently available FDA-approved neural stem cell lines for a regeneration trial in transverse myelitis is immune rejection. The patient’s own immune system will try to remove foreign cells that are surgically transplanted into the damaged spinal cord. This could result in more inflammation in the spinal cord and greater damage. Current protocols call for using graft rejection immunosuppression medications that are used in patients with kidney and heart transplants with only minor modifications.

One potential way around the immune rejection problem is to use human induced pluripotent stem cells (hiPSC). HiPSCs are individualized stem cells created from skin cells and treated in a dish to regress back into an embryonic stem cell-like state. The cells can then be differentiated forward into any cell type in the body. Thus, using hiPSC technology, scientists can turn a patient’s skin cells into its own brain cells. The patient’s immune system still recognizes the newly formed brain cells as self, and not foreign.

Dr. Steven A. Goldman, Professor and Chairman of the Department of Neurology at the University of Rochester, Neurologist-in-Chief of Strong Memorial Hospital and Chief of the Department’s Division of Cell and Gene Therapy, demonstrated that hiPSCs harvested from skin can successfully develop into myelin producing cells. The hiPSCs he used were created in 2008 and 2009 from surface skin cells and deeper skin cells called fibroblasts. They were regressed into embryonic state and frozen for use in Dr. Goldman’s present study.

Dr. Goldman grew the cells in a petri dish and exposed them to various hormones and growth factors in a 6-step process that took between 110 and 150 days. This process led to the development of two types of neural stem cells, myelin-producing oligodendrocytes and supportive astrocytes. The oligodendrocyte stem cells were purified for injection into special mice, the shiverer mouse, that are genetically unable to produce any myelin of their own. Over the next 3-5 months, the purified hiPSCs migrated throughout the mouse brain and produced copious amounts of myelin, enough to keep the animals alive far longer than the 4 months the untreated animals survived. This study is similar to Dr. Goldman’s previous publication in 2004 where he showed that human stem cells have the ability to produce myelin in the shiverer mouse, except that in this study, he used hiPSC lines instead of fetal or adult stem cells.

The implications of this study are that hiPSCs are capable of producing myelin just like other stem cells. In considering safety issues related to immune responses and graft rejection, hiPSCs are a better option. This study makes a strong argument against critics of hiPSCs who are concerned these cells will not perform as well.

To learn more about the potential of stem cells, Dr. Michael Levy wrote a piece in our March 2012 journal – click here

MLevy-1Dr. Michael Levy, a member of the Medical and Scientific Council of the TMA, is an Assistant Professor of Neurology at Johns Hopkins University and leads the NMO Center.  Dr. Levy specializes in taking care of patients with neuro-immunologic diseases including multiple sclerosis, transverse myelitis, optic neuritis and neuromyelitis optica. In the laboratory, Dr. Levy¹s research focus is on the development of neural stems for regenerative therapy in these diseases. He uses rat and mouse models to test the survival, differentiation and functional capacity of human neural stem cells to improve neurologic function in post-inflammatory conditions. The goal of his laboratory and clinical effort is to translate the basic science stem cell work to a human trial in transverse myelitis and other neuro-immunologic diseases.