Abstract
BackgroundA promising therapeutic strategy for amyotrophic lateral sclerosis (ALS) is the use of cell-based therapies that can protect motor neurons and thereby retard disease progression. We recently showed that a single large dose (25×106 cells) of mononuclear cells from human umbilical cord blood (MNC hUCB) administered intravenously to pre-symptomatic G93A SOD1 mice is optimal in delaying disease progression and increasing lifespan. However, this single high cell dose is impractical for clinical use. The aim of the present pre-clinical translation study was therefore to evaluate the effects of multiple low dose systemic injections of MNC hUCB cell into G93A SOD1 mice at different disease stages.Methodology/Principal FindingsMice received weekly intravenous injections of MNC hUCB or media. Symptomatic mice received 106 or 2.5×106 cells from 13 weeks of age. A third, pre-symptomatic, group received 106 cells from 9 weeks of age. Control groups were media-injected G93A and mice carrying the normal hSOD1 gene. Motor function tests and various assays determined cell effects. Administered cell distribution, motor neuron counts, and glial cell densities were analyzed in mouse spinal cords. Results showed that mice receiving 106 cells pre-symptomatically or 2.5×106 cells symptomatically significantly delayed functional deterioration, increased lifespan and had higher motor neuron counts than media mice. Astrocytes and microglia were significantly reduced in all cell-treated groups.Conclusions/SignificanceThese results demonstrate that multiple injections of MNC hUCB cells, even beginning at the symptomatic disease stage, could benefit disease outcomes by protecting motor neurons from inflammatory effectors. This multiple cell infusion approach may promote future clinical studies.
Highlights
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by a loss of upper and lower motor neurons
Of the total 108 G93A SOD1 mice used in the study, seven mice (Group1 – one, Group 2 – two, Group 3 – three, Group 4 – one) were excluded due to death precipitated by conditions other than disease progression, anesthetic complications during cell or media administrations
We evaluated the effects of multiple MNC Human umbilical cord blood (hUCB) cell injections into a G93A SOD1 mouse model of amyotrophic lateral sclerosis (ALS) at different disease stages
Summary
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by a loss of upper and lower motor neurons. The clinical presentation and underlying pathology of sALS and fALS are similar. A promising therapeutic strategy for amyotrophic lateral sclerosis (ALS) is the use of cell-based therapies that can protect motor neurons and thereby retard disease progression. We recently showed that a single large dose (256106 cells) of mononuclear cells from human umbilical cord blood (MNC hUCB) administered intravenously to pre-symptomatic G93A SOD1 mice is optimal in delaying disease progression and increasing lifespan. This single high cell dose is impractical for clinical use. The aim of the present pre-clinical translation study was to evaluate the effects of multiple low dose systemic injections of MNC hUCB cell into G93A SOD1 mice at different disease stages
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.