# Platelet-Regulated Immune Responses in Neonates Following Transfusion

> **NIH NIH R21** · UNIVERSITY OF ROCHESTER · 2021 · $192,500

## Abstract

Project Summary
 This proposal brings together the expertise of the Palis and Morrell labs in developmental
hematopoiesis and platelet biology, respectively, in order to gain a mechanistic understanding of the
complications associated with platelet transfusions into neonates. Thrombocytopenia is common in
newborns, particularly in premature infants. Platelet transfusions are prophylactically used to prevent
bleeding, but recent clinical studies have shown that the transfusion of platelets to neonates, while perhaps
reducing bleeding risk, can increase serious and sometimes long-term complications including
retinopathies, necrotizing enterocolitis and sepsis. We therefore seek to better understand the mechanisms
that contribute to these platelet-mediated adverse outcomes. Our long-term aim is to mitigate their adverse
effects of platelet transfusions and ultimately develop ex vivo modified platelets, including platelets derived
from induced pluripotent stem (iPS) cells, to increase the safety of transfusion therapy for neonates.
 We have discovered that, compared to adult platelets, neonatal platelets differentially express several
immune-related molecules. These data lead to our overall hypothesis that the transfusion of adult platelets
into neonates drives an inflammatory phenotype in monocyte leading to adverse complications. This
hypothesis is further supported by our preliminary data utilizing a novel murine neonatal transfusion model,
where monocyte inflammatory responses were enhanced by adult, but not neonatal, platelet transfusions.
We will utilize this in vivo model to define platelet-driven immune responses, focusing on the causative role
of platelet-derived immune mediators in the activation of monocytes both in vitro and in vivo. Finally, to
obtain a deeper understanding of the developmental program of adult versus neonatal platelets, we will
initiate comparative studies of murine and human platelet transcriptomes and proteomes, focusing on the
differential expression of immune-related molecules.
 Completion of this project will establish fundamental insights regarding the developmental biology of
platelets and their ability to interact with the immune system of neonates. This knowledge will lay the
groundwork for future studies in re-programming platelet immune functions to improve safety and efficacy of
platelet transfusions both for neonates and adults.

## Key facts

- **NIH application ID:** 10217253
- **Project number:** 5R21HL153409-02
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** CRAIG N MORRELL
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $192,500
- **Award type:** 5
- **Project period:** 2020-07-15 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10217253

## Citation

> US National Institutes of Health, RePORTER application 10217253, Platelet-Regulated Immune Responses in Neonates Following Transfusion (5R21HL153409-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10217253. Licensed CC0.

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