Regenerative therapy for hippocampal degenerative diseases: lessons from preclinical studies

Abstract

Increase in life expectancy has put neurodegenerative diseases on the rise. Amongst these, degenerative diseases involving hippocampus like Alzheimer's disease (AD) and temporal lobe epilepsy (TLE) are ranked higher as it is vulnerable to excitotoxicity induced neuronal dysfunction and death resulting in cognitive impairment. Modern medicines have not succeeded in halting the progression of these diseases rendering them incurable and often fatal. Under such scenario, regenerative studies employing stem cells or their by-products in animal models of AD and TLE have yielded encourageing results. This review focuses on the distinct cell types, such as hippocampal cell lines, neural precursor cells, embryonic stem cells derived neural precursor cells, induced pluripotent stem cells, induced neurons and mesenchymal stem cells, which can be employed to rescue hippocampal functions in neurodegenerative diseases like AD and TLE. Besides, the divergent mechanisms through which cell based therapy confer neuroprotection, current impediments and possible improvements in stem cell transplantation strategies are discussed. Authors are aware of the voluminous literature available on this issue and have made a sincere attempt to put forth the current status of research in the field of cell based therapy concurrently discussing the promise it holds for combating neurodegenerative diseases like AD and TLE in the near future. Copyright © 2015 John Wiley & Sons, Ltd.

Exploiting Heparan Sulfate Proteoglycans in Human Neurogenesis—Controlling Lineage Specification and Fate

“…However, the inflammatory microenvironment present at the injury site is hostile to neuroblast survival, limiting the capacity of the brain for self-regeneration and repair (Galindo et al, 2011 ). In the case of neurodegeneration, the rate of cell loss exceeds that of generation of new neurons (Venugopal et al, 2017 ). With the balance of damage to regeneration unable to be met by the brain, obtaining neural cells from exogenous sources able to augment or direct repair is an important potential therapeutic tool (Neirinckx et al, 2013 ).…”

“…This includes embryoid body (EB) formation in the presence of retinoic acid or conditioned media (Kurosawa, 2007 ); or through a monolayer culture system in the presence of FGF and notch ligands together with the bone morphogenetic protein (BMP) antagonist, noggin (Ying et al, 2003 ; Kunath et al, 2007 ). In a mouse temporal lobe epilepsy model, ESC-derived neural progenitor cells (NPCs) displayed enhanced survival and differentiation in the GCL when transplanted into the dentate gyrus (Venugopal et al, 2017 ). Interestingly, a study using an Alzheimer's disease mouse model has shown transplantation of undifferentiated ESCs led to extensive teratoma formation (Wang et al, 2006 ).…”

“…Interestingly, a study using an Alzheimer's disease mouse model has shown transplantation of undifferentiated ESCs led to extensive teratoma formation (Wang et al, 2006 ). This, combined with ethical and political issues surrounding the derivation of ESCs from embryonic tissue poses hurdles for their use in clinical practice (Venugopal et al, 2017 ).…”

3D Bioprinting for Spinal Cord Injury Repair

“…Spinal cord injury (SCI) is considered to be one of the most challenging central nervous system injuries, the serious complications and high rates of paraplegia caused by SCIs have brought great burden to individuals, families, and society ( Venugopal et al, 2017 ). Once damaged or degenerated, nerve cells cannot be self-repaired, which results in the permanent loss of function.…”

Progress in the molecular mechanisms of genetic epilepsies using patient‐induced pluripotent stem cells

“…Thus, iPSCs can provide a reliable platform for the study of the molecular mechanisms of GE. [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] Studies using iPSC technology to investigate the molecular mechanisms of GE have included studies focusing on Rett syndrome, Dravet syndrome, Phelan-McDermid syndrome (PMDS), and fragile X syndrome (FxS). Classic GE syndromes include childhood absence epilepsy (CAE), juvenile absence epilepsy (JAE), juvenile myoclonic epilepsy (JME), and epilepsy with generalized tonic-clonic seizures alone (GTCS).…”