‘Implantation site and lesion topology determine efficacy of a human neural stem cell line in a rat model of chronic stroke’
From Stem Cells
Commentary by Carla B. Mellough
Stroke remains one of the leading causes of mortality and adult disability in developed nations1-3. For the survivors of stroke, the resulting disability is often persistent in nature and severely affects an individual’s quality of life, with the additional possibility of recurrent stroke events a grim reality. Over the past four decades, while the incidence of stroke has declined in high-income countries there has been a greater than 100% increase in low to middle-income countries, highlighting the magnitude of this cardiovascular problem.3 Yet strategies to maximize recovery and help improve patient outcome following stroke have made little progress, with only 3% of patients currently gaining any benefit from existing treatment strategies, such as the use of thrombolytic agents.4 There is therefore an obvious need for the development of restorative therapies which would help to address the loss of neurons and glia in the brain following stroke. For a cell-based therapeutic approach, determining the optimal cell type for use that will apply to a broad cross section of stroke patients while giving consistent results and minimal complications is key. Various cell types have been tested in experimental stroke ranging from embryonic, mesenchymal and neural stem cells to human umbilical cord blood, in addition to some less obvious candidates such as adipose and menstrual blood cells, with preclinical studies indicating varying positive outcomes but, importantly, that many different cell types can elicit encouraging results.4,5 Many of the cell types that have been tested appear to exert their effects not by cell replacement, but by their neurotrophic and anti-inflammatory effects on affected tissues, and therefore act by minimizing damage and providing protection to brain tissues. Neuronal precursors derived from human embryonic stem cells (hESCs) tested in a rat model of stroke were shown to elicit some functional recovery,6 but the application of such strategies to the clinic remain somewhat hampered by the potential tumorigenicity of any residual stem cells which may be transplanted alongside more differentiated cell types. Until measures to reduce this potentiality are optimized, human neural stem cells (hNSCs) represent a good alternative. In the current study, Smith et al.7 report on the use of a human cortical neuroepithelium-derived hNSC line (CTX0E03) which, in previous studies has shown efficacy in improving sensorimotor function in a dose-dependent manner and, unlike other hNSCs, shows limited migration capacity thereby providing a locally-acting cell based therapy which makes it potentially safer than other hNSC types. This work represents a collaborative study from Kings College London, the UK based company ReNeuron and the University of Pittsburgh in Pennsylvania.