LPS Priming of Stromal Cells to Generate LPS-Specific Exosome Educated Macrophages

Abstract

The disclosure relates to an ex vivo generated population of educated macrophages specific to LPS and methods of making and using such macrophages.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims priority to U.S. Provisional Application No. 62 / 629,479, filed Feb. 12, 2018, which is incorporated herein by reference in its entirety.STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH[0002]This invention was made with government support under CA014520 awarded by the National Institutes of Health. The government has certain rights in the invention.BACKGROUND[0003]Radiation, delivered therapeutically, accidentally, or maliciously, can lead to an acute radiation syndrome (ARS) with life threatening toxicities. High-dose radiation causes damage to highly proliferative cells such as those found in the bone marrow, GI-tract and skin. Current standard of care involves supporting victims with antibiotics and transfusions until they can undergo an allogeneic bone marrow transplant (BMT) from a suitable donor. Unfortunately, the entire BMT process can often take weeks to identify and collect cells from a donor, and are diff...

AI Technical Summary

Benefits of technology

This patent describes a method for generating anti-inflammatory macrophages and monocytes by co-culturing a mesenchymal stromal cell with an extracellular vesicle isolated from a mesenchymal stromal cell exposed to lipopolysaccharide (LPS). The resulting macrophages and monocytes exhibit an anti-inflammatory phenotype with high expression of CD206, PD-L1, PD-L2, CD16, CD73, CD86, and low expression of CD16 and IL-6. This method can be used for the treatment of inflammatory diseases and has shown promising results in animal models.

Problems solved by technology

Radiation, delivered therapeutically, accidentally, or maliciously, can lead to an acute radiation syndrome (ARS) with life threatening toxicities.

High-dose radiation causes damage to highly proliferative cells such as those found in the bone marrow, GI-tract and skin.

Unfortunately, the entire BMT process can often take weeks to identify and collect cells from a donor, and are difficult to perform on a large-scale in the event of a widespread exposure.

Moreover, allogeneic BMTs have their own set of complications, including engraftment failure, opportunistic infections and / or graft-versus-host-disease (GVHD), making them potentially as toxic as the radiation injury itself.

Unfortunately, for these factors to be effective the patient's own hematopoietic stem cells have to be spared from radiation effects.

However, while therapeutic MSCs show promise, they often fail to demonstrate clear efficacy in many clinical trials, and have not yet been approved to treat ARS.

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