Transplantation of mesenchymal stem cells in ALS

ALS Centre, Department of Neurology, Eastern Piedmont University, "Maggiore della Carità" Hospital, Novara, Italy. Electronic address: .
Progress in brain research (Impact Factor: 2.83). 11/2012; 201:333-59. DOI: 10.1016/B978-0-444-59544-7.00016-0
Source: PubMed


Amyotrophic lateral sclerosis (ALS) is a devastating incurable, neurodegenerative disease that targets motor neurons (MNs) in the primary motor cortex, brainstem, and spinal cord, leading to muscle atrophy, paralysis, and death due to respiratory failure within 2-5 years. Currently, there is no cure for ALS. The development of a therapy that can support or restore MN function and attenuate toxicity in the spinal cord provides the most comprehensive approach for treating ALS. Mesenchymal stem cells might be suitable for cell therapy in ALS because of their immunomodulatory and protective properties. In this review, the authors discuss the major challenges to the translation of in vitro and animal studies of MSCs therapy in the clinical setting.

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    • "Another strictly related question is the toxicity and the possible malignant transformation and cytogenetic aberrations of stem cells. The literature quite agrees on the safety of stem cells [62, 63] but by a careful analysis of the preclinical papers reported here, it emerges that this aspect has not been specifically or adequately considered. In our work [46] we injected different doses of hASC reaching the highest dose of 6 × 106 cells/mice and we did not register any macroscopic adverse effect: no animal died or changed its habits/behaviour and no side effects have been observed. "
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    ABSTRACT: Neuropathic pain (NP) is a highly invalidating disease resulting as consequence of a lesion or disease affecting the somatosensory system. All the pharmacological treatments today in use give a long lasting pain relief only in a limited percentage of patients before pain reappears making NP an incurable disease. New approaches are therefore needed and research is testing stem cell usage. Several papers have been written on experimental neuropathic pain treatment using stem cells of different origin and species to treat experimental NP. The original idea was based on the capacity of stem cell to offer a totipotent cellular source for replacing injured neural cells and for delivering trophic factors to lesion site; soon the researchers agreed that the capacity of stem cells to contrast NP was not dependent upon their regenerative effect but was mostly linked to a bidirectional interaction between the stem cell and damaged microenvironment resident cells. In this paper we review the preclinical studies produced in the last years assessing the effects induced by several stem cells in different models of neuropathic pain. The overall positive results obtained on pain remission by using stem cells that are safe, of easy isolation, and which may allow an autologous transplant in patients may be encouraging for moving from bench to bedside, although there are several issues that still need to be solved.
    BioMed Research International 08/2014; 2014:470983. DOI:10.1155/2014/470983 · 1.58 Impact Factor
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    • "These studies documented the occurrence of increased cell proliferation during experimental models of spinal cord disease, mostly following traumatic spinal cord injury ([7] for a comprehensive review). Only a few studies analyzed endogenous spinal cord stem cells during ALS [8] [9] [10] [11] and being the most recent studies rather focused on detailing the transplantation of exogenous stem cells previously induced to differentiate towards a neuron-like phenotype [12] [13] [14] [15] [16]. "
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    ABSTRACT: In the present paper, we analyze the cell number within lamina X at the end stage of disease in a G93A mouse model of ALS; the effects induced by lithium; the stem-cell like phenotype of lamina X cells during ALS; the differentiation of these cells towards either a glial or neuronal phenotype. In summary we found that G93A mouse model of ALS produces an increase in lamina X cells which is further augmented by lithium administration. In the absence of lithium these nestin positive stem-like cells preferentially differentiate into glia (GFAP positive), while in the presence of lithium these cells differentiate towards a neuron-like phenotype ( β III-tubulin, NeuN, and calbindin-D28K positive). These effects of lithium are observed concomitantly with attenuation in disease progression and are reminiscent of neurogenetic effects induced by lithium in the subependymal ventricular zone of the hippocampus.
    04/2014; 2014(2):670756. DOI:10.1155/2014/670756
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    • "The technique and route of delivery of MSCs in ALS must also be considered in developing the most effective treatment approach [50]. Each potential mechanism discussed previously may be achievable in one or more anatomical compartments, and selection of the most efficient compartment is critical. "
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    ABSTRACT: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting the neuromuscular system and does not have a known singular cause. Genetic mutations, extracellular factors, non-neuronal support cells, and the immune system have all been shown to play varied roles in clinical and pathological disease progression. The therapeutic plasticity of mesenchymal stem cells (MSCs) may be well matched to this complex disease pathology, making MSCs strong candidates for cellular therapy in ALS. In this review, we summarize a variety of explored mechanisms by which MSCs play a role in ALS progression, including neuronal and non-neuronal cell replacement, trophic factor delivery, and modulation of the immune system. Currently relevant techniques for applying MSC therapy in ALS are discussed, focusing in particular on delivery route and cell source. We include examples from in vitro, preclinical, and clinical investigations to elucidate the remaining progress that must be made to understand and apply MSCs as a treatment for ALS.
    Stem Cell Research & Therapy 03/2014; 5(32). DOI:10.1186/scrt421 · 3.37 Impact Factor
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