Bone Marrow Mesenchymal Stem Cells: Agents of Immunomodulation and Neuroprotection

Ibrahim      Kassis; Adi      Vaknin-Dembinsky; Dimitrios      Karussis

Abstract

Mesenchymal stromal cells (MSC) are part of the bone marrow stem cells repertoire which also includes the main stem cells population of the bone marrow, the hematopoietic stem cells. The main role of MSCs is to support hematopoiesis but they can also give rise to cells of the mesodermal layers. Recently, significant interactions between MSCs and cells from the immune system have been demonstrated: MSCs were found to downregulate T and B lymphocytes, natural killer cells (NK) and antigen presenting cells through various mechanisms, including cell-to cell interaction and soluble factor production. Besides the immunomodulatory effects, MSCs were shown to possess additional stem cells features, such as the self-renewal potential and multipotency. Their debatable transdifferentiation potential to cells of the endo- and exo-dermal layer, including cells of the CNS, may explain in part their reported neuroprotective effects. Studies in vitro and in vivo (in cells cultures and in animal models) have indicated neuroprotective effects. MSCs are believed to promote functional recovery following CNS injury or inflammation, by producing trophic factors that may facilitate the mobilization of endogenous neural stem cells and promote the regeneration or the survival of the affected neurons. These immunomodulatory and neuroprotective features could make MSCs potential candidates for future therapeutic modalities in immune-mediated and neurodegenerative diseases.

Keywords: Bone marrow, mesenchymal stem cells, immunomodulation, neuroprotection, neurodegenerative diseases, multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), neurotrophic factors, bone marrow stem cells, hema-topoiesis, B lymphocytes,, natural killer cells (NK), Bone marrow,, mesenchymal stem cells,, multi-ple sclerosis (MS), amyotrophic lateral sclerosis, endodermal, ectodermal, stroke, brain trauma,, Parkinson, ’, s disease, (neo-neurogenesis)., regulatory T cells, den-dritic cells (DC), cytokines, chemokines, versus host disease (GVHD),, Effect on T Lymphocytes, indoleamine, 2,3-dioxygenase (IDO), hepatic growth factor (HGF), Prostaglandin E2, cyclooxygenase (COX) enzymes, tumour necrosis factor- (TNF-), chemotaxis, Antigen Presenting Cells, experimental autoimmune en-cephalomyelitis (EAE), myelin oligodendrocyte protein, myelin antigens, neurogenesis, axotomised neurons, retinal ganglion cells, ciliary neu-rotrophic factor (CNTF), nuerotrophin-3, brain derived neurotrophic factor (BDNF), remyelination, neuroblastoma, osteogenesis imperfecta, myocardial infarction, leukodystrophies, cancer chemotherapy complications, super-paramagnetic iron oxide