Brain Inj. 2015;29(12):1497-510. doi: 10.3109/02699052.2015.1053525. Epub 2015 Aug 5.
Effects of local administration of allogenic adipose tissue-derived mesenchymal stem cells on functional recovery in experimental traumatic brain injury.
1a Pediatric Intensive Critical Care, Hospital Niño Jesús , Madrid , Spain .
2b Hospital Niño Jesús, Instituto Investigación Sanitaria La Princesa , Madrid , Spain , and.
3c Department of Neurology and Stroke Centre, Neuroscience and Cerebrovascular Research Laboratory , La Paz University Hospital Neuroscience Area of IdiPAZ (Health Research Institute), Autonoma University of Madrid , Madrid , Spain.
Traumatic brain injury (TBI) is the leading cause of mortality and morbidity in paediatric patients after the first year of life. The aim of this study was to evaluate effects of locally administered allogeneic mesenchymal stem cells (MSC), in the acute period after a TBI.
MSC were isolated from peritoneal fat of healthy rats, expanded in vitro and labelled with the green fluorescent protein. Rats were placed in one of three experimental groups: (1) CONTROL: TBI, (2) IP-CONTROL: TBI + local saline and (3) IP-Treat: TBI + 2 × 10(5) MSC 24 hours after receiving a moderate, unilateral, controlled cortical impact. Motor and cognitive behavioural tests were performed to evaluate functional recovery. Histological examination and immunohistochemistry were used to identify cell distribution.
Improved performance was found on motor tests in the MSC-treated group compared to control groups. MSC were found in the perilesional area and their number decreased with time after transplantation. MSC treatment increased the cell density in the hippocampus (CA3 pyramidal cells and granule cells in the dentate gyrus) and enhanced neurogenesis in this area.
MSC cell therapy resulted in better recovery of motor function compared with the control group. This cellular therapy might be considered for patients suffering from TBI.
Animal model; MSCs (mesenchymal stem cells); TBI (traumatic brain injury); cell therapy; children; neurogenesis; pediatric intensive care medicine
Biochimie. 2013 Dec;95(12):2257-70. doi: 10.1016/j.biochi.2013.08.004. Epub 2013 Aug 27.
The role of mesenchymal stromal cells in spinal cord injury, regenerative medicine and possible clinical applications.
1Institute of Experimental Medicine, Academy of Science of the Czech Republic, Prague, Czech Republic; Department of Neuroscience, 2nd Faculty of Medicine, Charles University, Prague, Czech Republic.
Diseases of the central nervous system still remain among the most challenging pathologies known to mankind, having no or limited therapeutic possibilities and a very pessimistic prognosis. Advances in stem cell biology in the last decade have shown that stem cells might provide an inexhaustible source of neurons and glia as well as exerting a neuroprotective effect on the host tissue, thus opening new horizons for tissue engineering and regenerative medicine. Here, we discuss the progress made in the cell-based therapy of spinal cord injury. An emphasis has been placed on the application of adult mesenchymal stromal cells (MSCs). We then review the latest and most significant results from in vitro and in vivo research focusing on the regenerative/neuroprotective properties of MSCs. We also attempt to correlate the effect of MSCs with the pathological events that are taking place in the nervous tissue after SCI. Finally, we discuss the results from preclinical and clinical trials involving different routes of MSC application into patients with neurological disorders of the spinal cord.
Copyright © 2013. Published by Elsevier Masson SAS.
ALS; AMSCs; BDNF; BMSC; CNS; CST; Cell-based therapy; Clinical trials; ESCs; GDNF; GRP; GVHD; IGF-1; MN; MRI; MSC; MV; NF; NGF; NMJ; NPCs; NTF; Neuroprotection; OMgp; PNN; Regeneration; SC; SCI; SOD1; Stem cells; VEGF; adipose-derived MSCs; amyotrophic lateral sclerosis; bone marrow MSC; brain-derived neurotrophic factor; central nervous system; corticospinal tracts; embryonic stem cells; glia derived neurotrophic factor; glial restricted precursors; graft-versus-host disease; hNSC; hUCB; human neural stem/progenitor cells; human umbilical cord blood; iPSCs; induced pluripotent cells; insulin growth factor-1; magnetic resonance imaging; mesenchymal stromal cells; microvesicles; motoneurones; neural growth factor; neural progenitor cells; neurofilament; neuromuscular junction; neurotrophic factors; oligodendrocytemyelin glycoprotein; perineuronal nets; spinal cord; spinal cord injury; superoxide dismutase 1 gene; vascular endothelial growth factor
World J Stem Cells. 2014 Apr 26;6(2):120-33. doi: 10.4252/wjsc.v6.i2.120.
Mesenchymal stem cells in the treatment of spinal cord injuries: A review.
1Venkata Ramesh Dasari, Krishna Kumar Veeravalli, Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, IL 61656, United States.
With technological advances in basic research, the intricate mechanism of secondary delayed spinal cord injury (SCI) continues to unravel at a rapid pace. However, despite our deeper understanding of the molecular changes occurring after initial insult to the spinal cord, the cure for paralysis remains elusive. Current treatment of SCI is limited to early administration of high dose steroids to mitigate the harmful effect of cord edema that occurs after SCI and to reduce the cascade of secondary delayed SCI. Recent evident-based clinical studies have cast doubt on the clinical benefit of steroids in SCI and intense focus on stem cell-based therapy has yielded some encouraging results. An array of mesenchymalstem cells (MSCs) from various sources with novel and promising strategies are being developed to improve function after SCI. In this review, we briefly discuss the pathophysiology of spinal cord injuries and characteristics and the potential sources of MSCs that can be used in the treatment of SCI. We will discuss the progress of MSCs application in research, focusing on the neuroprotective properties of MSCs. Finally, we will discuss the results from preclinical and clinical trials involving stem cell-based therapy in SCI.
Adipose tissue derived mesenchymal stem cells; Bone marrow stromal cells; Mesenchymal stem cells; Spinal cord injury; Umbilical cord derived mesenchymal stem cells
Neuroscience. 2013 Apr 16;236:55-65. doi: 10.1016/j.neuroscience.2012.12.066. Epub 2013 Jan 29.
Glial differentiation of human adipose-derived stem cells: implications for cell-based transplantation therapy.
Increasing evidence has shown that adipose-derived stem cells (ASCs) could transdifferentiate into Schwann cell (SC)-like cells to enhance nerve regeneration, suggesting potential new cell-based transplantation therapy for peripheral nerve injuries and neurodegenerative disorders. For the implementation of these results to the clinical setting, it is of great importance to establish the differentiation of human ASCs (hASCs) into a SC phenotype. In this study, we studied hASCs obtained from subcutaneous fat tissue of healthy donors. By a mixture of glial growth factors we differentiated them into Schwann cell-like cells (dhASCs). We then assessed their ability to act as Schwann cells in vitro and in vivo and also compared them with primary human Schwann cells (hSCs). Enzyme-linked immunosorbent assay showed that dhASCs secreted brain-derived neurotrophic factor (BDNF)/nerve growth factor (NGF) at a comparable level, and glial cell-derived neurotrophic factor (GDNF) at a level even higher than hSCs, whereas undifferentiated hASCs (uhASCs) secreted low levels of these neurotrophic factors. In co-culture with NG108-15 neuronal cells we found that both dhASCs and hSCs significantly increased the percentage of cells with neurites, the neurite length, and the number of neurites per neuron, whereas uhASCs increased only the percentage of cells with neurites. Finally, we transplanted green fluorescent protein (GFP)-labeled hASCs into the crushed tibial nerve of athymic nude rats. The transplanted hASCs showed a close association with PGP9.5-positive axons and myelin basic protein (MBP)-positive myelin at 8weeks after transplantation. Quantitative analysis revealed that dhASCs transplantation resulted in significantly improved survival and myelin formation rates (a 7-fold and a 10-fold increase, respectively) as compared with uhASCs transplantation. These findings suggest that hASCs took part in supporting and myelinating regenerating axons, and thus have achieved full glial differentiation in vivo. In conclusion, hASCs can differentiate into SC-like cells that possess a potent capacity to secrete neurotrophic factors as well as to form myelin in vivo. These findings make hASCs an interesting prospect for cell-based transplantation therapyfor various peripheral nerve disorders.