Mesenchymal Stem Cells Repair Neurotoxin Damage in an Animal Model

Preclinical work supports the use of mesenchymal stem cells to treat neurodegenerative disorders.

Researchers at Tel Aviv University have introduced and tracked mesenchymal stem cells as they migrate into the damaged areas of the brain in a neurotoxin rat model of Huntington’s Disease.

Mesenchymal stem cells are multi-potent cells that can develop into a variety of cell types. They are mainly found in the bone marrow. The researchers, led by Dr. Yoram Cohen, attached magnetic iron oxide nanoparticles to the stem cells so they could be tracked using the the in-vivo MRI at the Strauss Centre for Computational Neuro- Imaging. The stem cells were then injected in to the brains of rats which had been given a neurotoxin which mimics the damage seen in Huntington’s Disease.

Dr.Cohen and colleagues were able watch the stem cells migrating towards the diseased area of the brain in real time. "Cells that go toward a certain position that needs to be rescued are the best indirect proof that they are live and viable. If they can migrate towards the target, they are alive and can read chemical signaling,” explains Dr. Cohen.

He describes the significance of the work. “We have been able to prove that these stem cells travel within the brain, and only travel where they are needed. They read the chemical signaling of the tissue, which indicate areas of stress. And then they go and try to repair the situation."

Mesenchymal stem cells may become an important therapy for Huntington’s Disease, other neurodegenerative diseases, and stroke. A clinical trial is planned for HD patients and is expected tot start in about 18 months.

In April, Dr. Jan Nolta of the University of California, Davis, received a $2.75 million translational grant from The California Insitute for Regernerative Medicine (CIRM). The goal of CIRM is to fund promising projects which will translate basic research into stem cells into a cure in the clinic. Dr. Nolta and colleague Dr. Vickie Wheeler will use mesenchymal stem cells in a Phase I clinical trial. As the stem cells move through the affected areas of the brain, they will merge with and repair damaged brain cells and also reduce levels of the HD protein. Mesenchymal stem cells have not been associated with tumors and appear to be immunologically privileged.

Other reference:

University of Tel Aviv press release

Marsha L. Miller, Ph.D.
Migration of Neurotrophic Factors-Secreting Mesenchymal Stem Cells Toward a Quinolinic Acid Lesion as Viewed by Magnetic Resonance Imaging

Ofer Sadan, Noam Shemesh, Ran Barzilay, Merav Bahat-Stromza, Eldad Melamed, Yoram Cohen, and Daniel Offen

abstract

Stem cell-based treatment is a promising frontier for neurodegenerative diseases. We propose a novel protocol for inducing the differentiation of rat mesenchymal stem cells (MSCs) toward neurotrophic factor (NTF)-secreting cells as a possible neuroprotective agent. One of the major caveats of stem cell transplantation is their fate post-transplantation. To test the viability of the cells, we tracked the transplanted cells in vivo by magnetic resonance imaging (MRI) scans and validated the results by histology. MSCs went through a two-step medium-based differentiation protocol, followed by in vitro characterization using immunocytochemistry and immunoblotting analysis of the cell media. We examined the migratory properties of the cells in the quinolinic acid (QA)-induced striatal lesion model for Huntington's disease. The induced cells were labeled and transplanted posterior to the lesion. Rats underwent serial MRI scans to detect cell migration in vivo. On the 19th day, animals were sacrificed, and their brains were removed for immunostaining. Rat MSCs postinduction exhibited both neuronal and astrocyte markers, as well as production and secretion of NTFs. High-resolution two-dimensional and three-dimensional magnetic resonance images revealed that the cells migrated along a distinct route toward the lesion. The in vivo MRI results were validated by the histological study, which demonstrated that phagocytosis had only partially occurred and that MRI could correctly depict the status of the migrating cells. The results show that these cells migrated toward a QA lesion and therefore survived for 19 days post-transplantation. This gives hope for future research harnessing these cells for treating neurodegenerative diseases. Disclosure of potential conflicts of interest is found at the end of this article.

Stem Cells Vol. 26 No. 10 October 2008, pp. 2542 -2551