Faculty Collaboration Database

Donor-specific phenotypic variation in hiPSC cardiomyocyte-derived exosomes impacts endothelial cell function. Am J Physiol Heart Circ Physiol 2021 Mar 01;320(3):H954-H968

Date

01/09/2021

Pubmed ID

33416449

Pubmed Central ID

PMC8294700

DOI

10.1152/ajpheart.00463.2020

Scopus ID

2-s2.0-85102212257 (requires institutional sign-in at Scopus site)   9 Citations

Abstract

Exosomes are an important mechanism of cell-cell interaction in the cardiovascular system, both in maintaining homeostasis and in stress response. Interindividual differences that alter content in exosomes may play a role in cardiovascular disease pathology. To study the effect of interindividual cardiomyocyte (CM) variation, we characterized exosomal content in phenotypically diverse human induced pluripotent stem cell-derived CMs (hiPSC-CMs). Cell lines were generated from six participants in the HyperGEN cohort: three with left ventricular hypertrophy (LVH) and three with normal left ventricular mass (LVM). Sequence analysis of the intracellular and exosomal RNA populations showed distinct expression pattern differences between hiPSC-CM lines derived from individuals with LVH and those with normal LVM. Functional analysis of hiPSC-endothelial cells (hiPSC-ECs) treated with exosomes from both hiPSC-CM groups showed significant variation in response, including differences in tube formation, migration, and proliferation. Overall, treatment of hiPSC-ECs with exosomes resulted in significant expression changes associated with angiogenesis and endothelial cell vasculogenesis. However, the hiPSC-ECs treated with exosomes from the LVH-affected donors exhibited significantly increased proliferation but decreased tube formation and migration, suggesting angiogenic dysregulation.NEW & NOTEWORTHY The intracellular RNA and the miRNA content in exosomes are significantly different in hiPSC-CMs derived from LVH-affected individuals compared with those from unaffected individuals. Treatment of endothelial cells with these exosomes functionally affects cellular phenotypes in a donor-specific manner. These findings provide novel insight into underlying mechanisms of hypertrophic cell signaling between different cell types. With a growing interest in stem cells and exosomes for cardiovascular therapeutic use, this also provides information important for regenerative medicine.

Author List

Turner A, Aggarwal P, Matter A, Olson B, Gu CC, Hunt SC, Lewis CE, Arnett DK, Lorier R, Broeckel U

Authors

Ulrich Broeckel MD Chief, Center Associate Director, Professor in the Pediatrics department at Medical College of Wisconsin
Amy Turner Research Scientist I in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Case-Control Studies
Cell Differentiation
Cell Movement
Cell Proliferation
Cell Separation
Cells, Cultured
Exosomes
Female
Gene Expression Regulation
Humans
Hypertrophy, Left Ventricular
Induced Pluripotent Stem Cells
Male
MicroRNAs
Middle Aged
Myocytes, Cardiac
Neovascularization, Physiologic
Phenotype
RNA, Messenger
Signal Transduction
Tissue Donors
Transcriptome