Adult olfactory bulb neural precursor cell grafts provide temporary protection from motor neuron degeneration, improve motor function, and extend survival in amyotrophic lateral sclerosis mice.
Amyotrophic lateral sclerosis is a fatal disease caused by degeneration of motor neurons (MNs). We transplanted multipotent neural precursor cell (NPC)-neurospheres from mouse olfactory bulb (OB) into the spinal cord of transgenic mice that develop MN degeneration because of human mutant superoxide dismutase-1 (mSOD1). Adult NPCs were isolated from the OB core of transgenic mice expressing green fluorescent protein, human wild-type SOD1, or human mSOD1. mSOD1 mice received lumbar spinal cord transplants of OB-NPC neurospheres at preclinical stages of disease (70 days old). Control mSOD1 mice received dead cells or recombinant green fluorescent protein. OB-NPCs attenuated the loss of motor function and wasting. They delayed disease onset to approximately 117 days, compared with control onset at approximately 90 days. The lifespan of NPC recipient mice was extended (approximately 170 days) compared with the lifespan of controls (approximately 140 days). Transplanted OB-NPCs differentiated into large spinal neurons positive for choline acetyltransferase, interneurons, and glial cells. Loss of endogenous MNs was attenuated in mSOD1 mice with transplants. New neurons formed myelinated axons and synapses. NPC-derived neurons issued axons that grew into peripheral nerve. OB-NPCs also differentiated into oligodendrocytes and astrocytes that contacted neuronal processes. We conclude that transplantation of adult OB-NPCs is therapeutic for mouse amyotrophic lateral sclerosis.
Martin
Lee J
LJ
Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2196, USA. martinl@jhmi.edu
Liu
Zhiping
Z
D000690:Amyotrophic Lateral Sclerosis / Q000628:therapy*; D000818:Animals; D002454:Cell Differentiation; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D016253:Microscopy, Immunoelectron; D009046:Motor Neurons / Q000473:pathology*; D009154:Mutation; D009410:Nerve Degeneration / Q000517:prevention & control*; D009474:Neurons / Q000166:cytology / Q000637:transplantation*; D009830:Olfactory Bulb / Q000166:cytology / Q000637:transplantation; D016133:Polymerase Chain Reaction; D020127:Recovery of Function; D013116:Spinal Cord / Q000601:surgery; D033581:Stem Cell Transplantation; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1
C000606290:SOD1 protein, human; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1