Stem cell transplantation in neurological diseases: improving effectiveness in animal models

Abstract

Neurological diseases afflict a growing proportion of the human population. There are two reasons for this: first, the average age of the population (especially in the industrialized world) is increasing, and second, the diagnostic tools to detect these pathologies are now more sophisticated and can be used on a higher percentage of the population. In many cases, neurological disease has a pharmacological treatment which, as in the case of Alzheimer's disease, Parkinson's disease, Epilepsy, and Multiple Sclerosis can reduce the symptoms and slow down the course of the disease but cannot reverse its effects or heal the patient. In the last two decades the transplantation approach, by means of stem cells of different origin, has been suggested for the treatment of neurological diseases. The choice of slightly different animal models and the differences in methods of stem cell preparation make it difficult to compare the results of transplantation experiments. Moreover, the translation of these results into clinical trials with human subjects is difficult and has so far met with little success. This review seeks to discuss the reasons for these difficulties by considering the differences between human and animal cells (including isolation, handling and transplantation) and between the human disease model and the animal disease model.

Microglial polarization in posttraumatic epilepsy: Potential mechanism and treatment opportunity

“…Among these, the delivery of M2‐promoting cytokines by genetically modified cells and viral vector–based gene therapies seem promising and can be easily investigated for their potential in acquired epilepsies. Stem cell–based approaches are a promising new strategy for a range of human conditions, and have been trialed for cell replacement and modulating the levels of neuroprotective agents . Similarly, the viral vector–mediated modulation of inflammation could be used to modulate neuroinflammation after an epileptogenic brain insult, considering that these have been observed to be safe in mediating gene therapy in neurological conditions .…”

“…Cellular therapies, especially with stem cells of different regenerative capacities, have been trialed in neurological disorders with chronic loss of specific cell types, such as Parkinson disease and Alzheimer disease, as well as brain injury associated with ongoing neurodegeneration such as stroke and TBI. 96 Such therapies have also shown promising outcomes in epilepsy models administering the stem cells programmed to differentiate into GABAergic interneurons to counter the excessive network excitability. 97,98 Genetically modified cells have also been injected into the brain to continuously deliver different neuropeptides or other molecules with antiepileptic potential and have shown positive outcomes.…”

Advances in Stem Cell Research- A Ray of Hope in Better Diagnosis and Prognosis in Neurodegenerative Diseases

“…The genetic involvement of ubiquitin carboxy terminal hydrolase L1, serine threonine kinase 1, parkin, DJ-1, α-synuclein, and leucine-rich repeat kinase 2 have been reported in the case of genetically acquired familial PD (Dauer and Przedborski, 2003). Environmental influence in conjunction with age, genetic polymorphisms and chemical exposure predispose an individual toward sporadic PD, however the complex etiology is yet to be fully understood (Adami et al, 2014). Fitzmaurice et al showed that variation in Aldehyde dehydrogenase enhances the pesticide effect related to PD thereby proving that environmental influences work in conjunction with genetics (Fitzmaurice et al, 2014).…”

“…Ling et al gave evidence at the genetic level by reporting that FTD-ALS and ALS patients carry similar mutated genes (Lee and Huang, 2015). Many gene mutations are responsible for causing familial ALS such as mutations in PFN1, FUS/TLS (fused in sarcoma/translocation in liposarcoma), TARDBP or TDP-43 (TAR-DNA-binding protein 43), UBQLN2, C9ORF72, SOD1 (superoxide dismutase 1), HNRNPA1, OPTN, and VCP (Adami et al, 2014). Recently a new gene named TBK1 has been discovered which plays a crucial role in inflammation & autophagy which are inherently associated with ALS pathogenesis (Cirulli et al, 2015).…”

Stem cell treatment for age-related neurodegenerative diseases

“…The amount of stem cells, as well as the speed of neurogenesis in the adult CNS are not sufficient for the regeneration and repair of defects that exist in neurological diseases, although shown to stimulate neurogenesis of brain tissue damage, as well as the particular hormones and neurotransmitters, but also that there is a circulating population of stem cells in the blood, that could perform supplementation of NPC of adult CNS [25]. Possible therapeutic exogenous sources of stem cells are ESCs, FSCs, ASCs and iPSCs [26][27][28].…”