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Author Notes:

Correspondence Jonathan D. Glass, 101 Woodruff Circle, Atlanta, GA 30322. Tel: 404-727-3507; Fax: 404-778-3495; E-mail: jglas03@emory.edu

T. T., J. D. G.: experimental procedures, data analysis, and original draft of manuscript. M. G., D. S., D. S., D. B., R. B., H. G., C. H., E. F.: experimental procedures, data analysis, and final editing of manuscript. N. B., J. R., T. F.: surgical procedures and final editing of manuscript. K. J., T. H.: cell production and characterization and final editing of manuscript. M. P., J. B.: patient care and data collection and final editing of manuscript.

We are grateful to the patients and their families for participating in this trial for the development of ALS.

N. M. B.: personal fees, NeuralStem Inc., outside the current study; patents, licensed to NeuralStem Inc. T. H.: reports works for Neuralstem Inc. patents issued NeuralStem Inc. C. H.: personal fees from Roche Molecular Systems, Inc., unrelated to the current study. K. J.: personal fees from Neuralstem, Inc., during the study; personal fees and other from Neuralstem, Inc., outside the current study, patent issued Neuralstem, Inc. J. D. G.: grants from Neuralstem Inc.

Dr. Boulis reports personal fess from NeuralStem Inc, Outside the submitted work; in addition, Dr. Boulis has a patent floating cannula licensed to NeuralStem Inc, and a patent Spinal Platform licensed to NeuralStem Inc. Dr. Feldman reports grants from ALS Association, grants from NINDS. Dr. Glass reports grants from Neuralstem Inc, grants from NINDS. Dr. Hazel has a patent Transplantation of human neural cells for treatment of neurodegenerative conditions issued, and a patent Methods of treating amyotrophic lateral sclerosis (ALS) issued. Dr. Hill reports personal fees from Roche Molecular Systems.

Dr. Johe reports personal fees from Neuralstem, Inc., during the conduct of the study; personal fees and other from Neuralstem, Inc., outside the submitted work; In addition, Dr. Johe has a patent Neuralstem, Inc. issued.


Research Funding:

This study was funded by Neuralstem, Inc. and by a grants from the National Institute of Neurological Disorders and Stroke (R01 NS077982), the National Institute of Aging (P50 AG025688), and the National Institute of Environmental Health Sciences (T32 ES12870).

Analysis of graft survival in a trial of stem cell transplant in ALS.

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Journal Title:

Annals of Clinical and Translational Neurology


Volume 1, Number 11


, Pages 900-908

Type of Work:

Article | Final Publisher PDF


Objective The first US Food and Drug Administration–approved clinical trial to treat amyotrophic lateral sclerosis (ALS) with neural stem cell–based therapy is in progress. The goal of the current study was to identify and assess the survival of human spinal cord–derived neural stem cells (HSSCs) transplanted into the spinal cord in patients with ALS. Methods Spinal cords transplanted with HSSCs were examined from six autopsy cases. Homogenized tissues were interrogated for the presence of donor versus recipient DNA using real-time PCR methods (qPCR). Fluorescence in situ hybridization (FISH) was performed using DNA probes for XY chromosomes to identify male donor HSSCs in one female case, and immunohistochemistry (IHC) was used to characterize the identified donor cells. Results Genomic DNA from donor HSSCs was identified in all cases, comprising 0.67–5.4% of total tissue DNA in patients surviving 196 to 921 days after transplantation. In the one female patient a “nest” of cells identified on H&E staining were XY-positive by FISH, confirming donor origin. A subset of XY-positive cells labeled for the neuronal marker NeuN and stem cell marker SOX2. Interpretation This is the first study to identify human neural stem cells transplanted into a human spinal cord. Transplanted HSSCs survived up to 2.5 years posttransplant. Some cells differentiated into neurons, while others maintained their stem cell phenotype. This work is a proof of concept of the survival and differentiation of human stems cell transplanted into the spinal cord of ALS patients.

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© 2014 by the authors

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