Abstract
Exosomes are known for their ability to transport nucleic acid, lipid, and protein molecules, which allows for communication between cells and tissues. The cargo of the exosomes can have a variety of effects on a wide range of targets to mediate biological function. Pancreatic islet transplantation is a minimally invasive cell replacement therapy to prevent or reverse diabetes mellitus and is currently performed in patients with uncontrolled type 1 diabetes or chronic pancreatitis. Exosomes have become a focus in the field of islet transplantation for the study of diagnostic markers of islet cell viability and function. A growing list of miRNAs identified from exosomes collected during the process of isolating islets can be used as diagnostic biomarkers of islet stress and damage, leading to a better understanding of critical steps of the isolation procedure that can be improved to increase islet yield and quality. Exosomes have also been implicated as a possible contributor to islet graft rejection following transplantation, as they carry donor major histocompatibility complex molecules, which are then processed by recipient antigen-presenting cells and sensed by the recipient immune cells. Exosomes may find their way into the therapeutic realm of islet transplantation, as exosomes isolated from mesenchymal stem cells have shown promising results in early studies that have seen increased viability and functionality of isolated and grafted islets in vitro as well as in vivo. With the study of exosomes still in its infancy, continued research on the role of exosomes in islet transplantation will be paramount to understanding beta cell regeneration and improving long-term graft function.
Highlights
Diabetes mellitus is characterized by chronic hyperglycemia due to partial or absolute insulin deficiency or pancreatic beta cell dysfunction and/or insulin inaction [1,2,3]
We provide an overview of the roles of exosomes in allogeneic and autologous antigen presentation to the recipient immune system, exosome cargo, and the utility of exosomes for diagnosis and therapy
“Damage-induced exo-miRNA” increased in response to hypoxia, streptozotocin, and cytokine stress after 24 h Elevated 24 h following transplant Elevated throughout islet isolation “Stress-induced exo-miRNA” increased after 6 h ctyokine and hypoxic stress Elevated 24 h following transplant Elevated throughout islet isolation “Damage-induced exo-miRNA” increased after 24 h cytokine and hypoxic stress Elevated 24 h following transplant Elevated throughout islet isolation “Stress-induced exo-miRNA” increased after 6 h ctyokine and hypoxic stress Elevated 24 h following transplant Elevated throughout islet isolation Elevated throughout islet isolation Increased in normoglycemic xenotransplant mice Increase associated with normoglycemia following xenotransplant Increase associated with normoglycemia following xenotransplant Increase associated with rejection following xenotransplant Increase associated with rejection following xenotransplant
Summary
Jordan Mattke 1, Srividya Vasu 2, Carly M. Exosomes have been implicated as a possible contributor to islet graft rejection following transplantation, as they carry donor major histocompatibility complex molecules, which are processed by recipient antigen-presenting cells and sensed by the recipient immune cells. Exosomes may find their way into the therapeutic realm of islet transplantation, as exosomes isolated from mesenchymal stem cells have shown promising results in early studies that have seen increased viability and functionality of isolated and grafted islets in vitro as well as in vivo.
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