Intraspinal Injection of Human Umbilical Cord Blood-Derived Cells Is Neuroprotective in a Transgenic Mouse Model of Amyotrophic Lateral Sclerosis

Abstract

Background: Amyotrophic lateral sclerosis (ALS) is characterized by progressive degeneration of motor neurons in the spinal cord, brain stem and motor cortex and has only marginal therapeutic options. Adult stem cells have recently come into the focus of neurological research. While replacement of motor neurons by stem cells currently appears not feasible, there is evidence that non-neuronal cells can be neuroprotective. Objective: Therefore, we evaluated the effects of direct intraspinal administration of human umbilical cord blood cells in a G93A transgenic mouse model of ALS before (day 40) and after symptom onset (day 90). Methods: Treatment effects were assessed by survival analysis, behavioral tests, histological and biochemical analyses. Results: Treatment at early stages increased survival, led to significant improvements in motor performance and significantly reduced motor neuron loss and astrogliosis in the spinal cord. Interestingly females tended to respond better to treatment than males. Conclusion: This study confirms the neuroprotective potential of human umbilical cord blood cells and encourages further investigations.

Inflammatory hypertrophic cauda equina following intrathecal neural stem cell injection

“…Animal studies involving intraspinal and intrathecal administration of stem cells have generally shown safety and some promising results in the treatment of central nervous system disease . Human trials are still in very early stages and are mostly aimed at demonstrating the safety of intrathecal or intraspinal stem cell delivery.…”

Erratum: Inflammatory hypertrophic cauda equina following intrathecal neural stem cell injection

“…[14][15][16] Human trials are still in very early stages and are mostly aimed at demonstrating the safety of intrathecal or intraspinal stem cell delivery. To this point, human studies have reported common side effects of transient fevers, headaches, increased spasticity, mild sensory changes in the legs and sacral region, and neuropathic pain.…”

Stem cells for ALS: An overview of possible therapeutic approaches

“…The neurotherapeutic effect was also achieved by genetically modified hUBCs (overexpressing trophic factors), which, when retro‐orbitaly delivered, not only support symptomatic outcomes in ALS mice but also differentiate into astrocytes (Islamov et al, 2015; Rizvanov et al, 2011). Other studies have shown that, in the early stage of the disease, injection of hUBCs improved motor function and neuromuscular transmission, decreased the loss of MNs and extended survival of transgenic mice (Knippenberg et al, 2012b; Souayah et al, 2012). In order for the transplantation of hUBCs in a preclinical study of ALS to be effective, these cells need to be injected multiple times (Willenbrock et al, 2012) and tracked by safe in vivo methods to reach the degenerated region of the CNS (Garbuzova‐Davis et al, 2012b).…”