Spinal cord infusion of stem cells in amyotrophic lateral sclerosis: Magnetic resonance spectroscopy shows metabolite improvement in the precentral gyrus

Santos, J.M. García; Inuggi, Alberto; Espuch, Joaquín Gómez; Iniesta, Francisca; Blanquer, Miguel; Moraleda, José Marı́a

doi:10.1016/j.jcyt.2016.03.296

Cited by 11 publications

(4 citation statements)

References 36 publications

(60 reference statements)

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“…The combination of 1 H-MRS and DTI to diagnose ALS yields a high positive likelihood ratio (6.20) and low negative likelihood ratio (0.08), with potentially useful sensitivity and specificity of 90 and 85%, respectively (271). Although publications assessing longitudinal NAA changes have reached inconsistent conclusions (272–274), NAA concentration has also been used as a marker of treatment response in a number of clinical trials (275–281).…”

Section: Central Nervous Systemmentioning

confidence: 99%

Biomarkers in Motor Neuron Disease: A State of the Art Review

et al. 2019

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Motor neuron disease can be viewed as an umbrella term describing a heterogeneous group of conditions, all of which are relentlessly progressive and ultimately fatal. The average life expectancy is 2 years, but with a broad range of months to decades. Biomarker research deepens disease understanding through exploration of pathophysiological mechanisms which, in turn, highlights targets for novel therapies. It also allows differentiation of the disease population into sub-groups, which serves two general purposes: (a) provides clinicians with information to better guide their patients in terms of disease progression, and (b) guides clinical trial design so that an intervention may be shown to be effective if population variation is controlled for. Biomarkers also have the potential to provide monitoring during clinical trials to ensure target engagement. This review highlights biomarkers that have emerged from the fields of systemic measurements including biochemistry (blood, cerebrospinal fluid, and urine analysis); imaging and electrophysiology, and gives examples of how a combinatorial approach may yield the best results. We emphasize the importance of systematic sample collection and analysis, and the need to correlate biomarker findings with detailed phenotype and genotype data.

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Section: Central Nervous Systemmentioning

confidence: 99%

Biomarkers in Motor Neuron Disease: A State of the Art Review

et al. 2019

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“…Four weeks after the infusion, the cells remained between the basement membrane and the muscle fibers, but we observed an increase in the number of motoneurons that innervate the treated muscle, and in the survival rate of spinal cord motoneurons by axonal-guided retrograde neurotrophism [20]. Furthermore, in a clinical study with a magnetic resonance spectroscopy, after the injection of BM-MSCs at the spinal cord in ALS patients, we show a distant beneficial effect in the precentral gyri in the brain [48].…”

Section: Discussionmentioning

confidence: 52%

Safety and Biodistribution of Human Bone Marrow-Derived Mesenchymal Stromal Cells Injected Intrathecally in Non-Obese Diabetic Severe Combined Immunodeficiency Mice: Preclinical Study

Quesada

García‐Bernal

Pastor

et al. 2019

Tissue Eng Regen Med

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BACKGROUND: Mesenchymal stromal cells (MSCs) have potent immunomodulatory and neuroprotective properties, and have been tested in neurodegenerative diseases resulting in meaningful clinical improvements. Regulatory guidelines specify the need to perform preclinical studies prior any clinical trial, including biodistribution assays and tumourigenesis exclusion. We conducted a preclinical study of human bone marrow MSCs (hBM-MSCs) injected by intrathecal route in Non-Obese Diabetic Severe Combined Immunodeficiency mice, to explore cellular biodistribution and toxicity as a privileged administration method for cell therapy in Friedreich's Ataxia. METHODS: For this purpose, 3 9 10 5 cells were injected by intrathecal route in 12 animals (experimental group) and the same volume of culture media in 6 animals (control group). Blood samples were collected at 24 h (n = 9) or 4 months (n = 9) to assess toxicity, and nine organs were harvested for histology and safety studies. Genomic DNA was isolated from all tissues, and mouse GAPDH and human b2M and b-actin genes were amplified by qPCR to analyze hBM-MSCs biodistribution. RESULTS: There were no deaths nor acute or chronic toxicity. Hematology, biochemistry and body weight were in the range of normal values in all groups. At 24 h hBM-MSCs were detected in 4/6 spinal cords and 1/6 hearts, and at 4 months in 3/6 hearts and 1/6 brains of transplanted mice. No tumours were found. CONCLUSION: This study demonstrated that intrathecal injection of hBM-MSCs is safe, non toxic and do not produce tumors. These results provide further evidence that hBM-MSCs might be used in a clinical trial in patients with FRDA.

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“…The colony-initiating cells were denoted as colony-forming units-fibroblast (CFU-F), which were later identified in human bone marrow aspirates [ 2 , 3 ]. Clonal analyses of ex vivo expanded human CFU-F were also found to undergo self-renewal, support a hematopoietic stem cell niche and facilitate wound repair, as well as exhibit immunomodulatory properties [ 4 , 5 , 6 , 7 , 8 ]. These stromal precursors have subsequently been referred to as skeletal stem cells, mesenchymal stem/stromal cells (MSC), stromal precursor cells and bone marrow-derived mesenchymal stromal cells (BMSC).…”

Section: Characterisation Of Mscmentioning

confidence: 99%

Impact of Environmental and Epigenetic Changes on Mesenchymal Stem Cells during Aging

Smith

Shirazi

Cakouros

et al. 2023

IJMS

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Many crucial epigenetic changes occur during early skeletal development and throughout life due to aging, disease and are heavily influenced by an individual’s lifestyle. Epigenetics is the study of heritable changes in gene expression as the result of changes in the environment without any mutation in the underlying DNA sequence. The epigenetic profiles of cells are dynamic and mediated by different mechanisms, including histone modifications, non-coding RNA-associated gene silencing and DNA methylation. Given the underlining role of dysfunctional mesenchymal tissues in common age-related skeletal diseases such as osteoporosis and osteoarthritis, investigations into skeletal stem cells or mesenchymal stem cells (MSC) and their functional deregulation during aging has been of great interest and how this is mediated by an evolving epigenetic landscape. The present review describes the recent findings in epigenetic changes of MSCs that effect growth and cell fate determination in the context of aging, diet, exercise and bone-related diseases.

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Spinal cord infusion of stem cells in amyotrophic lateral sclerosis: Magnetic resonance spectroscopy shows metabolite improvement in the precentral gyrus

Cited by 11 publications

References 36 publications

Biomarkers in Motor Neuron Disease: A State of the Art Review

Biomarkers in Motor Neuron Disease: A State of the Art Review

Safety and Biodistribution of Human Bone Marrow-Derived Mesenchymal Stromal Cells Injected Intrathecally in Non-Obese Diabetic Severe Combined Immunodeficiency Mice: Preclinical Study

Impact of Environmental and Epigenetic Changes on Mesenchymal Stem Cells during Aging

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