The differentiation of mesenchymal stem cells (MSC) into acetylcholine secreted motor neuron-like cells, followed by elongation of the cell axon, is a promising treatment for spinal cord injury and motor neuron cell dysfunction in mammals. Differentiation is induced through a pre-induction step using Beta- mercaptoethanol (BME) followed by four days of induction with retinoic acid and sonic hedgehog. This process results in a very efficient differentiation of BM-MSCs into motor neuron-like cells. Immunocytochemistry showed that these treated cells had specific motor neural markers: microtubule associated protein-2 and acetylcholine transferase. The ability of these cells to function as motor neuron cells was assessed by measuring acetylcholine levels in a culture media during differentiation. High-performance liquid chromatography (HPLC) showed that the differentiated cells were functional. Motor neuron axon elongation was then induced by adding different concentrations of a nerve growth factor (NGF) to the differentiation media. Using a collagen matrix to mimic the natural condition of neural cells in a three-dimensional model showed that the MSCs were successfully differentiated into motor neuron-like cells. This process can efficiently differentiate MSCs into functional motor neurons that can be used for autologous nervous system therapy and especially for treating spinal cord injuries.
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http://dx.doi.org/10.1016/j.jchemneu.2016.07.003 | DOI Listing |
Nat Commun
January 2025
Department of Bioengineering, The Grainger College of Engineering, University of Illinois Urbana-Champaign, Urbana, IL, USA.
An abnormal expansion of a GGGGCC (GC) hexanucleotide repeat in the C9ORF72 gene is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), two debilitating neurodegenerative disorders driven in part by gain-of-function mechanisms involving transcribed forms of the repeat expansion. By utilizing a Cas13 variant with reduced collateral effects, we develop here a high-fidelity RNA-targeting CRISPR-based system for C9ORF72-linked ALS/FTD. When delivered to the brain of a transgenic rodent model, this Cas13-based platform curbed the expression of the GC repeat-containing RNA without affecting normal C9ORF72 levels, which in turn decreased the formation of RNA foci, reduced the production of a dipeptide repeat protein, and reversed transcriptional deficits.
View Article and Find Full Text PDFCNS Neurosci Ther
January 2025
Dongguan Key Laboratory of Stem Cell and Regenerative Tissue Engineering, the First Dongguan Affiliated Hospital, School of Basic Medical Sciences, Guangdong Medical University, Dongguan, China.
Aims: Neuron death is caused primarily by apoptosis after spinal cord injury (SCI). Autophagy, as a cellular response, can maintain cellular homeostasis to reduce apoptosis. We aimed to investigate the effect and the mechanism of vimentin knockdown on autophagy and neural recovery after SCI.
View Article and Find Full Text PDFFront Chem
December 2024
Department of Algology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Introduction: Compression of the nerve root by a lumbar disc herniation can cause radiating pain in the lower limbs, and the nerve root decompression treatment may leave some patients with motor dysfunction and reduced sensory function. Studies have shown that nerve growth factor (NGF) can promote nerve growth and repair, but high doses, long duration, and immune response have become bottlenecks of its clinical application.
Methods: To overcome this obstacle, we developed Prussian blue (PBs) nanoparticles with the bio-delivery function and antioxidant effects of nanoenzymes.
Biochem Biophys Res Commun
January 2025
Laboratory of Medical Therapeutics and Molecular Therapeutics, Japan. Electronic address:
A GGGGCC hexanucleotide repeat expansion (HRE) within the C9orf72 gene is a major causative factor in amyotrophic lateral sclerosis (ALS). This aberrant HRE results in the generation of five distinct dipeptide repeat proteins (DPRs). Among the DPRs, poly-PR accumulates in the nucleus and exhibits particularly strong toxicity to motor and cortical neurons.
View Article and Find Full Text PDFJ Cell Mol Med
November 2024
Center for Rehabilitation Medicine, Department of Neurosurgery, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, China.
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