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Publications of the Week

Augmenting Emergency Granulopoiesis with CpG Conditioned Mesenchymal Stromal Cells in Murine Neutropenic Sepsis

By October 28, 2020November 2nd, 2020No Comments

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This week we profile a recent publication in Blood Advances from Dr. Julie Ng (pictured center) and the laboratories of Dr.
James Lederer (left) and Dr. Mark Perrella (right) at Brigham and Women’s Hospital and Harvard Medical School.

Can you provide a brief overview of your lab’s current research focus?

Dr. Lederer’s laboratory is interested in investigating the immunologic mechanisms of trauma and radiation injury, and therapeutic strategies to mitigate the consequent immune dysregulation to reduce morbidity and mortality from opportunistic infections. Dr. Perrella’s laboratory is interested in the mechanism of action and therapeutic use of mesenchymal stromal cells in sepsis. Together they have a combined interest in using mesenchymal stromal cells and their secreted paracrine factors as a radiation countermeasure to prevent opportunistic infections and complications in people who have been exposed to survivable radiation doses.

What is the significance of the findings in this publication?

Emergency granulopoiesis, or the de novo generation of neutrophils in response to a systemic infection through proliferation of myeloid progenitor cells, is an important fundamental host response to severe infections. In this paper, we demonstrate that bone marrow mesenchymal stromal cells (MSCs), known to support the hematopoietic niche, secrete paracrine factors that can augment emergency granulopoiesis — an effect that is enhanced when MSCs are preconditioned with CpG, a toll-like receptor (TLR) 9 agonist.  This paper is the first description of the ability of mesenchymal stromal cells to contribute to the process of emergency granulopoiesis in vivo. Furthermore, we demonstrate that neutrophils exposed to MSCs are functionally distinct – with increased phagocytosis and decreased production of neutrophil extracellular traps (NETs), which reduces organ damage.

What are the next steps for this research?

The next steps for this research are to understand the mechanisms of action of these paracrine factors on bone marrow stem and progenitor cells.

This work was funded by:

This research work was supported by funding from the National Institutes of Health (NIH) grants # T32HL007633-29, U01AI138318, R01GM118456, and R01GM136804 and as part of the NIH NIAID Radiation and Nuclear Countermeasures Program (RNCP).

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