Combo Bone Marrow Cell Transplant Seen to Benefit Mice in ALS Model

Combo Bone Marrow Cell Transplant Seen to Benefit Mice in ALS Model
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Transplanting a combination of two types of modified bone marrow cells eased motor deficits and prolonged survival in a mouse model of amyotrophic lateral sclerosis (ALS), researchers reported.

Their study, “Enhancing the therapeutic efficacy of bone marrow-derived mononuclear cells with growth factor-expressing mesenchymal stem cells for ALS in mice,” was published in iScience.

Stem cell therapy and regenerative medicine are areas of research aiming to develop treatments that can repair or replace damaged tissue. In the context of ALS, the aim of such therapies is to restore functionality to the damaged nervous system.

Previous research conducted at the Shiga University of Medical Science, in Japan, revealed that transplanting stem cell factor-activated mononuclear cells (MNCs, a type of bone marrow cell) can limit inflammation in the nervous system of ALS mice. But treatment benefits were minimal, likely because the extent to which the transplanted cells could enter and survive in a mouse’s spinal cord was limited.

Other studies investigated mesenchymal stem cells (MSCs, another type of bone marrow cell) that had been modified to express high levels of certain signaling molecules — those promoting nerve cell growth — as potential ALS therapies, with some promising results.

These modified MSCs, which produce hepatocyte growth factor (HGF), glial cell line-derived neurotrophic factor (GDNF), and insulin-like growth factor (IGF), are called HAC-MSCs.

“HAC-MSCs are expected to improve the environment and the niche surrounding neurons in the spinal cord of ALS. This might provide successful engraftment of bone marrow-derived MNCs in ALS mouse model,” the Shiga researchers wrote.

These researchers used a mouse model of ALS, caused by a mutation in the gene SOD1, to investigate the combined use of these two bone marrow-derived cells.

Eight-week-old female mice were treated with both HAC-MSCs and MNCs, or with each individually, while untreated mice were used as controls.

Mice given either HAC-MSCs or MNCs individually did not have significantly different average lifespans (median of about 20 weeks) compared to control mice (17 weeks). These individual treatments also did not significantly alter performance on the rotarod test, which measures coordination, or affect body weight, a surrogate measure of muscle atrophy.

However, mice treated with both HAC-MSCs and MNCs lived significantly longer (22 weeks) on average than control mice. They also showed significantly higher body weight starting one week after receiving the combination, and better rotarod test scores at several points later in the study.

Tissue analysis of the mice’s spinal cords showed greater preservation of neurons in cell-treated mice relative to control mice. Mice treated with both HAC-MSCs and MNCs had the greatest extent of neuronal preservation.

Combination treatment also reduced the extent of gliosis, or the activation of certain immune cells in the central nervous system that damages neurons, and showed evidence of preserving muscle fibers. Of note, these effects were more evident when mice were in later disease stages.

Further analysis showed that mice given the stem cell combination had greater numbers of MNCs in their spinal cords, compared with mice given MNCs alone or mice given unmodified MSCs in addition to MNCs. These findings support the idea that HAC-MSCs can promote the ability of MNCs to enter the spinal cord.

“This study showed that a combined bone marrow transplantation (BMT) of MNCs and growth factor-expressing MSCs (HAC-MSCs) enhanced the effect of BMT therapy of MNCs on ALS disease progression and survival in mice models,” the researchers concluded.

They added that, while this approach shows promise, additional studies are needed to more fully understand the biological mechanisms of the combination treatment, and to ensure it would be safe for human use.

Marisa holds an MS in Cellular and Molecular Pathology from the University of Pittsburgh, where she studied novel genetic drivers of ovarian cancer. She specializes in cancer biology, immunology, and genetics. Marisa began working with BioNews in 2018, and has written about science and health for SelfHacked and the Genetics Society of America. She also writes/composes musicals and coaches the University of Pittsburgh fencing club.
Total Posts: 45
Inês holds a PhD in Biomedical Sciences from the University of Lisbon, Portugal, where she specialized in blood vessel biology, blood stem cells, and cancer. Before that, she studied Cell and Molecular Biology at Universidade Nova de Lisboa and worked as a research fellow at Faculdade de Ciências e Tecnologias and Instituto Gulbenkian de Ciência. Inês currently works as a Managing Science Editor, striving to deliver the latest scientific advances to patient communities in a clear and accurate manner.
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Marisa holds an MS in Cellular and Molecular Pathology from the University of Pittsburgh, where she studied novel genetic drivers of ovarian cancer. She specializes in cancer biology, immunology, and genetics. Marisa began working with BioNews in 2018, and has written about science and health for SelfHacked and the Genetics Society of America. She also writes/composes musicals and coaches the University of Pittsburgh fencing club.
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