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: 5.1). 01/2012; 201:333-59. DOI: 10.1016/B978-0-444-59544-7.00016-0
Source: PubMed

ABSTRACT 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.

  • Source
    [Show abstract] [Hide abstract]
    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 · 2.71 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Cell therapies aim to repair the mechanisms underlying disease initiation and progression, achieved through trophic effect or by cell replacement. Multiple cell types can be utilized in such therapies, including stem, progenitor or primary cells. This review covers the current state of cell therapies designed for the prominent disorders, including cardiovascular, neurological (Parkinson's disease, amyotrophic lateral sclerosis, stroke, spinal cord injury), autoimmune (Type 1 diabetes, multiple sclerosis, Crohn's disease), ophthalmologic, renal, liver and skeletal (osteoarthritis) diseases. Various cell therapies have reached advanced clinical trial phases with potential marketing approvals in the near future, many of which are based on mesenchymal stem cells. Advances in pluripotent stem cell research hold great promise for regenerative medicine. The information presented in this review is based on the analysis of the cell therapy collection detailed in LifeMap Discovery(®) (LifeMap Sciences Inc., USA) the database of embryonic development, stem cell research and regenerative medicine.
    Regenerative Medicine 09/2014; 9(5):649-72. DOI:10.2217/rme.14.35 · 3.50 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Amyotrophic lateral sclerosis (ALS) is a clinically heterogeneous disorder characterized by loss of motor neurons, resulting in paralysis and death. Multiple mechanisms of motor neuron injury have been implicated based upon the more than 20 different genetic causes of familial ALS. These inherited mutations compromise diverse motor neuron pathways leading to cell-autonomous injury. In the ALS transgenic mouse models, however, motor neurons do not die alone. Cell death is noncell-autonomous dependent upon a well orchestrated dialogue between motor neurons and surrounding glia and adaptive immune cells. The pathogenesis of ALS consists of 2 stages: an early neuroprotective stage and a later neurotoxic stage. During early phases of disease progression, the immune system is protective with glia and T cells, especially M2 macrophages/microglia, and T helper 2 cells and regulatory T cells, providing anti-inflammatory factors that sustain motor neuron viability. As the disease progresses and motor neuron injury accelerates, a second rapidly progressing phase develops, characterized by M1 macrophages/microglia, and proinflammatory T cells. In rapidly progressing ALS patients, as in transgenic mice, neuroprotective regulatory T cells are significantly decreased and neurotoxicity predominates. Our own therapeutic efforts are focused on modulating these neuroinflammatory pathways. This review will focus on the cellular players involved in neuroinflammation in ALS and current therapeutic strategies to enhance neuroprotection and suppress neurotoxicity with the goal of arresting the progressive and devastating nature of ALS.
    Journal of the American Society for Experimental NeuroTherapeutics 01/2015; 12(2). DOI:10.1007/s13311-014-0329-3 · 3.88 Impact Factor


Available from
May 31, 2014