Grafted murine induced pluripotent stem cells prevent death of injured rat motoneurons otherwise destined to die.

In this study the effects of undifferentiated murine iPSCs on damaged motoneurons were investigated following avulsion of the lumbar 4 (L4) ventral root, an injury known to induce the death of the majority of the affected motoneurons. Avulsion and reimplantation of the L4 ventral root (AR procedure) was accompanied by the transplantation of murine iPSCs into the injured spinal cord segment in rats. Control animals underwent ventral root avulsion and reimplantation, but did not receive iPSCs. The grafted iPSCs induced an improved reinnervation of the reimplanted ventral root by the host motoneurons as compared with the controls (number of retrogradely labeled motoneurons: 503 ± 38 [AR+iPSCs group] vs 48 ± 6 [controls, AR group]). Morphological reinnervation resulted in a functional recovery, i.e. the grafted animals exhibited more motor units in their reinnervated hind limb muscles, which produced a greater force than that in the controls (50 ± 2.1% vs 11.9 ± 4.2% maximal tetanic tension [% ratio of operated/intact side]). Grafting of undifferentiated iPCSs downregulated the astroglial activation within the L4 segment. The grafted cells differentiated into neurons and astrocytes in the injured cord. The grafted iPSCs, host neurons and glia were found to produce the cytokines and neurotrophic factors MIP-1a, IL-10, GDNF and NT-4. These findings suggest that, following ventral root avulsion injury, iPSCs are able to induce motoneuron survival and rege...
Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research

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In this study, researchers studied 438,952 participants in the UK Biobank, who had a total of 24,980 major coronary events - defined as the first occurrence of non-fatal heart attack, ischaemic stroke, or death due to coronary heart disease. They used an approach called Mendelian randomisation, which uses naturally occurring genetic differences to randomly divide the participants into groups, mimicking the effects of running a clinical trial. People with genes associated with lower blood pressure, lower LDL cholesterol, and a combination of both were put into different groups, and compared against those without thes...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Since the discovery of induced pluripotency more than a decade ago, researchers have been working towards the use of this technology to produce cells for use in tissue engineering and regenerative therapies. Induced pluripotent stem cells are functionally equivalent to embryonic stem cells; given suitable recipes and methods for the surrounding environment and signals, they can be made to generate any of the cell types in the body. The cornea of the eye is a comparatively simple starting point for tissue engineering, easier to work with in many ways, in generating tissues and in delivering cells to the patient. Here, the f...
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs
Induced pluripotent stem cells (iPSC) [1] have been applied to clinical regenerative cell therapies such as the macular degeneration of the retina [2], spinal cord injury [3] and heart failure [4] et al. As use in autologous settings is hampered by the high time and cost requirements of the individual production of iPSC, an iPSC banking system which collects HLA typed cells from cord blood banks, marrow donor registries and HLA matched platelet donor registries has been proposed [5-8], and tissue transplantation generated from iPSC through banking in allogeneic settings has just been performed [8].
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Source Type: research
Abstract Spinal cord injury (SCI) causes irreversible functional loss of the affected population. The incidence of SCI keeps increasing, resulting in huge burden on the society. The pathogenesis of SCI involves neuron death and exotic reaction, which could impede neuron regeneration. In clinic, the limited regenerative capacity of endogenous cells after SCI is a major problem. Recent studies have demonstrated that a variety of stem cells such as induced pluripotent stem cells (iPSCs), embryonic stem cells (ESCs), mesenchymal stem cells (MSCs) and neural progenitor cells (NPCs) /neural stem cells (NSCs) have therap...
Source: Current Stem Cell Research and Therapy - Category: Stem Cells Authors: Tags: Curr Stem Cell Res Ther Source Type: research
In this study, we designed SCI models in vivo and in vitro and then investigated the possible mechanism of successful repair by BMSCs-Exos. In vivo, we established one Sham group and two SCI model groups. The Basso, Beattie, Bresnahan (BBB) scores showed that BMSCs-Exos could effectively promote the recovery of spinal cord function. The results of the Nissl staining, immunohistochemistry, and TUNEL/NeuN/DAPI double staining showed that BMSCs-Exos inhibited neuronal apoptosis. Western blot analysis showed that the protein expression level of Bcl-2 was significantly increased in the BMSCs-Exos group compared with the PBS gro...
Source: Cell Transplantation - Category: Cytology Authors: Tags: Cell Transplant Source Type: research
Authors: Tian DZ, Deng D, Qiang JL, Zhu Q, Li QC, Yi ZG Abstract OBJECTIVE: To explore the repair of spinal cord injury (SCI) in rats by umbilical cord mesenchymal stem cells (UCMSCs) through the p38mitogen-activated protein kinase (MAPK) signaling pathway. MATERIALS AND METHODS: A total of 45 healthy adult male Sprague-Dawley rats weighing 180-220 g and aged 6-8 weeks old were randomly divided into group A (SCI model + transplantation of UCMSCs, n=15), group B (sham operation), and group C (SCI model + injection of an equal dose of DMEM, n=15) using a random number table. The morphology of spinal cord tissues ...
Source: European Review for Medical and Pharmacological Sciences - Category: Drugs & Pharmacology Tags: Eur Rev Med Pharmacol Sci Source Type: research
Authors: Chen Y, Lian XH, Liao LY, Liu YT, Liu SL, Gao Q Abstract OBJECTIVE: To analyze the mechanism of action by which the bone marrow mesenchymal stem cells (BMMSCs) repair the spinal cord injury (SCI) in rats via the Notch signaling pathway. MATERIALS AND METHODS: A total of 75 male rats aged about 12 weeks old were equally divided into group A (sham operation group), group B (model group), and group C (model group + BMMSCs). The SCI model was established by Allen's method, and the differences in presenilin-1, Hes1 and Notch proteins among the three groups of rats were evaluated via immunohistochemical stai...
Source: European Review for Medical and Pharmacological Sciences - Category: Drugs & Pharmacology Tags: Eur Rev Med Pharmacol Sci Source Type: research
The issue with first generation cell therapies for regenerative medicine is that transplanted cells near entirely fail to engraft into tissue. There are exceptions, but for the most part, the cells used in therapy die rather than take up productive work to enhance tissue function. Where benefits occur, they are mediated by the signals secreted by the transplanted cells in the brief period they remain alive. Mesenchymal stem cell therapies that reduce chronic inflammation for some period of time are an example of the type. They are good at that outcome of reduced inflammation, but highly unreliable when it comes to any othe...
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs
CONCLUSIONS H₂O₂ can damage the stemness ability of BMSCs at a concentration of 200-300 uM. PMID: 31353362 [PubMed - in process]
Source: Medical Science Monitor - Category: Research Tags: Med Sci Monit Source Type: research
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Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: Original Article Source Type: research
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