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Series GSE88845 Query DataSets for GSE88845
Status Public on Oct 18, 2016
Title Transplant tissue specfic exosome platform for noninvasive monitoring of immunologic rejection [miRNA]
Platform organism synthetic construct
Sample organism Homo sapiens
Experiment type Non-coding RNA profiling by array
Summary In transplantation, there is a critical need for non-invasive biomarker platforms for monitoring immunologic rejection. We hypothesized that transplanted tissues release donor specific exosomes into recipient circulation/ bodily fluids, and that the quantitation and profiling of their intra-exosomal cargoes would constitute a novel biomarker platform for monitoring rejection. We tested this hypothesis in a human into mouse xenogeneic islet transplant model, and validated the concept in clinical settings of islet and renal transplantation. In the xenogeneic model, islet transplant exosomes in recipient blood were quantified over long-term follow-up using anti-human leukocyte antigen (HLA) antibody that is only expressed on human islets (p=1.6x10-14). Transplant islet exosomes were purified using anti-HLA antibody conjugated beads and their cargoes contained bona fide islet endocrine hormone markers insulin, glucagon, and somatostatin. Rejection led to significant decrease in transplant islet exosome signal (p=4x10-15), along with distinct changes in its microRNA and proteomic profiles prior to appearance of hyperglycemia. In the clinical settings of islet (n=5) and renal (n=5) transplantation, donor exosomes with respective tissue specificity for islet β cells and renal epithelial cells were reliably characterized in recipient plasma over follow-up (up to 5 years; p=0.0001). Collectively, these findings demonstrate the biomarker potential of transplant exosome characterization for providing a non-invasive window into the conditional state of the transplant tissue.
Overall design We assessed an in vivo read-out of TISE cargo as compared to its transplanted human islet tissue counterpart. Transplant islet exosomes from two independent experiments were analyzed. Small RNA microarray profiling of islet exosomes and islet graft tissue was performed. Next, we attempted small RNA profiling of R (rejection)-xeno samples, but because of the low TISE levels from a single sample we had to pool transplant islet exosomes from 5 animals for microarray analysis.
Contributor(s) Vallabhajosyula P, Korutla L, Habertheuer A, Yu M, Rostami S, Yuan C, Reddy S, Liu C, Korutla V, Koeberlein B, Trofe-Clark J, Rickels MR, Naji A
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Submission date Oct 17, 2016
Last update date May 02, 2017
Contact name Prashanth Vallabhajosyula
Phone 215 459 0487
Organization name University of Pennsylvania
Department Surgery
Street address 3400 Spruce Street
City Philadelphia
State/province PA
ZIP/Postal code 19104
Country USA
Platforms (1)
GPL19117 [miRNA-4] Affymetrix Multispecies miRNA-4 Array
Samples (3)
GSM2350026 Exosome profiles TISE_miRNA
GSM2350027 Islet graft tissue_miRNA
GSM2350028 Exosome profiles R-xeno_miRNA
This SubSeries is part of SuperSeries:
GSE88846 Transplant tissue specfic exosome platform for noninvasive monitoring of immunologic rejection
BioProject PRJNA348762

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE88845_RAW.tar 2.1 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table

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