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Stem Cell Transplants May Advance ALS Treatment By Repairing Blood-Spinal Cord Barrier

Summary: According to researchers, bone marrow stem cell transplants helped repair damage to the blood spinal cord barrier in mouse models of ALS. This helped improve motor functions and nervous system conditions.

Source: USF Health.

University of South Florida study finds ALS mice improved with stem cell therapy; first step for science in finding better treatment.

Researchers at the University of South Florida show in a new study that bone marrow stem cell transplants helped improve motor functions and nervous system conditions in mice with the disease Amyotrophic Lateral Sclerosis (ALS) by repairing damage to the blood-spinal cord barrier.

In a study recently published in the journal Scientific Reports, researchers in USF’s Center of Excellence for Aging and Brain Repair say the results of their experiment are an early step in pursuing stem cells for potential repair of the blood-spinal cord barrier, which has been identified as key in the development of ALS. USF Health Professor Svitlana Garbuzova-Davis, PhD, led the project.

Previous studies in development of various therapeutic approaches for ALS typically used pre-symptomatic mice.

“This is the first study advancing barrier repair that treats symptomatic mice, which more closely mirrors conditions for human patients,” Dr. Garbuzova-Davis said.

Using stem cells harvested from human bone marrow, researchers transplanted cells into mice modeling ALS and already showing disease symptoms. The transplanted stem cells differentiated and attached to vascular walls of many capillaries, beginning the process of blood-spinal cord barrier repair.

The stem cell treatment delayed the progression of the disease and led to improved motor function in the mice, as well as increased motor neuron cell survival, the study reported.

ALS is a progressive neurodegenerative disease that affects neuronal cells in the brain and the spinal cord, which send signals to control muscles throughout the body. The progressive degeneration of motor neuron cells leads to death from ALS. More than 6,000 Americans each year are diagnosed with the disease.

Because stem cells have the ability to develop into many different cell types in the body, researchers at USF’s Center of Excellence for Aging and Brain Repair, Department of Neurosurgery & Brain Repair have focused on using stem cells to restore function lost through neurodegenerative disorders or injuries.

Damage to the barrier between the blood circulatory system and the central nervous system has been recently recognized as a factor in ALS development, leading researchers to work on targeting the barrier for repair as a potential strategy for ALS therapy.

Image shows stem cells.

Using stem cells harvested from human bone marrow, researchers transplanted cells into mice modeling ALS and already showing disease symptoms. The transplanted stem cells differentiated and attached to vascular walls of many capillaries, beginning the process of blood-spinal cord barrier repair. NeuroscienceNews.com image is for illustrative purposes only.

In this study, the ALS mice were given intravenous treatments of one of three different doses of the bone marrow stem cells. Four weeks after treatment, the scientists determined improved motor function and enhanced motor neuron survival. The mice receiving the higher doses of stem cells fared better in the study, the researcher noted.

The transplanted stem cells had differentiated into endothelial cells – which form the inner lining of a blood vessel, providing a barrier between blood and spinal cord tissue — and attached to capillaries in the spinal cord. Furthermore, the researchers observed reductions in activated glial cells, which contribute to inflammatory processes in ALS.

About this neuroscience research article

Funding: The study was funded by the NIH/National Institute of Neurological Disorders and Stroke.

Source: Anne DeLotto Baier – USF Health
Image Source: NeuroscienceNews.com image is in the public domain.
Original Research: Full open access research for “Endothelial and Astrocytic Support by Human Bone Marrow Stem Cell Grafts into Symptomatic ALS Mice towards Blood-Spinal Cord Barrier Repair” by Svitlana Garbuzova-Davis, Crupa Kurien, Avery Thomson, Dimitri Falco, Sohaib Ahmad, Joseph Staffetti, George Steiner, Sophia Abraham, Greeshma James, Ajay Mahendrasah, Paul R. Sanberg & Cesario V. Borlongan in Scientific Reports. Published online April 13 2017 doi:10.1038/s41598-017-00993-0

Cite This NeuroscienceNews.com Article
USF Health “Stem Cell Transplants May Advance ALS Treatment By Repairing Blood-Spinal Cord Barrier.” NeuroscienceNews. NeuroscienceNews, 15 May 2017.
<http://neurosciencenews.com/stem-cell-als-repair-6679/>.
USF Health (2017, May 15). Stem Cell Transplants May Advance ALS Treatment By Repairing Blood-Spinal Cord Barrier. NeuroscienceNew. Retrieved May 15, 2017 from http://neurosciencenews.com/stem-cell-als-repair-6679/
USF Health “Stem Cell Transplants May Advance ALS Treatment By Repairing Blood-Spinal Cord Barrier.” http://neurosciencenews.com/stem-cell-als-repair-6679/ (accessed May 15, 2017).

Abstract

Endothelial and Astrocytic Support by Human Bone Marrow Stem Cell Grafts into Symptomatic ALS Mice towards Blood-Spinal Cord Barrier Repair

Vascular pathology, including blood-CNS barrier (B-CNS-B) damage via endothelial cell (EC) degeneration, is a recently recognized hallmark of Amyotrophic Lateral Sclerosis (ALS) pathogenesis. B-CNS-B repair may be a new therapeutic approach for ALS. This study aimed to determine effects of transplanted unmodified human bone marrow CD34+ (hBM34+) cells into symptomatic G93A mice towards blood-spinal cord barrier (BSCB) repair. Thirteen weeks old G93A mice intravenously received one of three different doses of hBM34+ cells. Cell-treated, media-treated, and control mice were euthanized at 17 weeks of age. Immunohistochemical (anti-human vWF, CD45, GFAP, and Iba-1) and motor neuron histological analyses were performed in cervical and lumbar spinal cords. EB levels in spinal cord parenchyma determined capillary permeability. Transplanted hBM34+ cells improved behavioral disease outcomes and enhanced motor neuron survival, mainly in high-cell-dose mice. Transplanted cells differentiated into ECs and engrafted within numerous capillaries. Reduced astrogliosis, microgliosis, and enhanced perivascular end-feet astrocytes were also determined in spinal cords, mostly in high-cell-dose mice. These mice also showed significantly decreased parenchymal EB levels. EC differentiation, capillary engraftment, reduced capillary permeability, and re-established perivascular end-feet astrocytes in symptomatic ALS mice may represent BSCB repair processes, supporting hBM34+ cell transplantation as a future therapeutic strategy for ALS patients.

“Endothelial and Astrocytic Support by Human Bone Marrow Stem Cell Grafts into Symptomatic ALS Mice towards Blood-Spinal Cord Barrier Repair” by Svitlana Garbuzova-Davis, Crupa Kurien, Avery Thomson, Dimitri Falco, Sohaib Ahmad, Joseph Staffetti, George Steiner, Sophia Abraham, Greeshma James, Ajay Mahendrasah, Paul R. Sanberg & Cesario V. Borlongan in Scientific Reports. Published online April 13 2017 doi:10.1038/s41598-017-00993-0

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