53 research outputs found
Analysis of graft survival in a trial of stem cell transplant in ALS
Objective The first US Food and Drug Administrationâapproved clinical trial to treat amyotrophic lateral sclerosis ( ALS ) with neural stem cellâbased therapy is in progress. The goal of the current study was to identify and assess the survival of human spinal cordâderived neural stem cells ( HSSC s) 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 realâtime 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 HSSC s was identified in all cases, comprising 0.67â5.4% of total tissue DNA in patients surviving 196 to 921Â days after transplantation. In the one female patient a ânestâ of cells identified on H&E staining were XY âpositive by FISH , confirming donor origin. A subset of XY âpositive cells labeled for the neuronal marker NeuN and stem cell marker SOX 2. Interpretation This is the first study to identify human neural stem cells transplanted into a human spinal cord. Transplanted HSSC s survived up to 2.5Â 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.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109593/1/acn3134.pd
- âŠ