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Review
, 120 (1), 29-40

Stem Cells in Human Neurodegenerative Disorders--Time for Clinical Translation?

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Review

Stem Cells in Human Neurodegenerative Disorders--Time for Clinical Translation?

Olle Lindvall et al. J Clin Invest.

Abstract

Stem cell-based approaches have received much hype as potential treatments for neurodegenerative disorders. Indeed, transplantation of stem cells or their derivatives in animal models of neurodegenerative diseases can improve function by replacing the lost neurons and glial cells and by mediating remyelination, trophic actions, and modulation of inflammation. Endogenous neural stem cells are also potential therapeutic targets because they produce neurons and glial cells in response to injury and could be affected by the degenerative process. As we discuss here, however, significant hurdles remain before these findings can be responsibly translated to novel therapies. In particular, we need to better understand the mechanisms of action of stem cells after transplantation and learn how to control stem cell proliferation, survival, migration, and differentiation in the pathological environment.

Figures

Figure 1
Figure 1. Stem cell–based therapies for PD.
PD leads to the progressive death of DA neurons in the substantia nigra and decreased DA innervation of the striatum, primarily the putamen. Stem cell–based approaches could be used to provide therapeutic benefits in two ways: first, by implanting stem cells modified to release growth factors, which would protect existing neurons and/or neurons derived from other stem cell treatments; and second, by transplanting stem cell–derived DA neuron precursors/neuroblasts into the putamen, where they would generate new neurons to ameliorate disease-induced motor impairments.
Figure 2
Figure 2. Stem cell–based therapies for ALS.
ALS leads to degeneration of motor neurons in the cerebral cortex, brainstem, and spinal cord. Stem cell–based therapy could be used to induce neuroprotection or dampen detrimental inflammation by implanting stem cells releasing growth factors. Alternatively, stem cell–derived spinal motor neuron precursors/neuroblasts could be transplanted into damaged areas to replace damaged or dead neurons.
Figure 3
Figure 3. Stem cell–based therapies for AD.
AD leads to neuronal loss in the basal forebrain cholinergic system, amygdala, hippocampus, and cortical areas of the brain; formation of neurofibrillary tangles; and β-amyloid protein accumulation in senile plaques. Stem cell–based therapy could be used to prevent progression of the disease by transplanting stem cells modified to release growth factors. Alternatively, compounds and/or antibodies could be infused to restore impaired hippocampal neurogenesis.
Figure 4
Figure 4. Stem cell–based therapies for stroke.
Ischemic stroke leads to the death of multiple neuronal types and astrocytes, oligodendrocytes, and endothelial cells in the cortex and subcortical regions. Stem cell–based therapy could be used to restore damaged neural circuitry by transplanting stem cell–derived neuron precursors/neuroblasts. Also, compounds could be infused that would promote neurogenesis from endogenous SVZ stem/progenitor cells, or stem cells could be injected systemically for neuroprotection and modulation of inflammation.
Figure 5
Figure 5. Stem cell–based therapies for spinal cord injury.
Spinal cord injury leads to interruption of ascending and descending axonal pathways, loss of neurons and glial cells, inflammation, and demyelination. Stem cell–based therapies could be used to treat individuals with spinal cord injury in several ways. First, transplanting stem cell–derived spinal neuroblasts could lead to the replacement of damaged or dead motor and other neurons. Second, transplanting stem cell–derived OPCs could promote remyelination. Last, transplanting stem cells modified to release different factors could counteract detrimental inflammation.

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