Concise Review: Prospects of Bone Marrow Mononuclear Cells and Mesenchymal Stem Cells for Treating Status Epilepticus and Chronic Epilepsy

Abstract

Mononuclear cells (MNCs) and mesenchymal stem cells (MSCs) derived from the bone marrow and other sources have received significant attention as donor cells for treating various neurological disorders due to their robust neuroprotective and anti-inflammatory effects. Moreover, it is relatively easy to procure these cells from both autogenic and allogenic sources. Currently, there is considerable interest in examining the usefulness of these cells for conditions such as status epilepticus (SE) and chronic epilepsy. A prolonged seizure activity in SE triggers neurodegeneration in the limbic brain areas, which elicits epileptogenesis and evolves into a chronic epileptic state. Because of their potential for providing neuroprotection, diminishing inflammation and curbing epileptogenesis, early intervention with MNCs or MSCs appears attractive for treating SE as such effects may restrain the development of chronic epilepsy typified by spontaneous seizures and learning and memory impairments. Delayed administration of these cells after SE may also be useful for easing spontaneous seizures and cognitive dysfunction in chronic epilepsy. This concise review evaluates the current knowledge and outlook pertaining to MNC and MSC therapies for SE and chronic epilepsy. In the first section, the behavior of these cells in animal models of SE and their efficacy to restrain neurodegeneration, inflammation, and epileptogenesis are discussed. The competence of these cells for suppressing seizures and improving cognitive function in chronic epilepsy are conferred in the next section. The final segment ponders issues that need to be addressed to pave the way for clinical application of these cells for SE and chronic epilepsy.

Inflamed synovial fluid induces a homeostatic response in bone marrow mononuclear cells in vitro: Implications for joint therapy

“…38,39 BMNC provide potent anti-inflammatory and pro-regenerative effects in injured tissues, including those with minimal regenerative capacity, such as the pancreas, central nervous system, and osteochondral defects. [40][41][42][43][44][45] BMNC can also induce homeostasis in chronically inflamed tissues refractory to other treatments, such as OAaffected joints and the respiratory system. 33,46 Macrophage progenitors are the primary cells in BMNC responsible for downregulating inflammation and may, through their homeostatic effects, provide therapeutic means for restoring joint homeostasis.…”

Impact of c-MYC expression on proliferation, differentiation, and risk of neoplastic transformation of human mesenchymal stromal cells

“…MSC from bone marrow and adipose tissue are an attractive cell source for regenerative medicine due to their high proliferation capacity [3], multi-lineage differentiation potential [4], and the trophic support of surrounding tissues through secretion of bioactive factors [5]. Therefore, MSC are not only applied for treatment of degenerative musculoskeletal diseases [6,7], but also for other stem cell-based therapies, such as steroid-refractory graft-versus-host disease (GvHD) [8], vascular diseases [9], neurological disorders [10], and others [11].…”

GABA-ergic cell therapy for epilepsy: Advances, limitations and challenges

“…In contrast, the purpose of GABA-ergic cell therapy is to replace lost GABA-ergic interneurons and thereby improve the inhibitory synaptic neurotransmission in the epileptic area of the brain (Hattiangady et al, 2008; Hunt et al, 2013; Cunningham et al, 2014; Henderson et al, 2014). On the other hand, the primary objective of systemic administration of bone marrow derived mononuclear cells and/or mesenchymal stem cells is to modulate the immune system to curtail the extent of chronic inflammation in the epileptic brain regions (Agadi and Shetty, 2015). Interestingly, all of these approaches have reduced the frequency and intensity of SRS in pre-clinical models of TLE and some have also produced positive effects on cognitive function.…”