# In vitro bioreactor system for platelet formation

> **NIH NIH R01** · TUFTS UNIVERSITY MEDFORD · 2020 · $347,420

## Abstract

Summary
In various human pathologies there are countless alterations in platelet production or function. Yet many of
these pathogenesis and the required targeted therapies remain unknown, resulting in palliative treatments. In
vivo, megakaryocytes associate with the bone marrow microvasculature where they extend proplatelets that
protrude through the vascular endothelium into the lumen and release platelets into the blood stream. The
scientific and clinical communities are actively searching for new modes to generate functional platelets ex
vivo to address clinical needs as well as for insight into fundamental studies of mechanisms. We hypothesize
that engineering a 3D bone marrow mimic, as demonstrated in our current grant, will propel mechanistic
understanding of platelet shedding and determine future protocols for therapeutic inquiry. To test our
hypothesis, in Aim 1 we will utilize non-thrombogenic silk protein biomaterial in a modified ex vivo three
dimensional (3D) tissue model of the bone marrow to study platelet release from megakaryocytes derived
from human induced pluripotent stem cells (hiPSCs); to compare with the results in the current grant using
megakaryocytes from umbilical cord blood progenitors. In Aim 2 we will focus on the use of the bioreactor
systems to study the effects of thrombopoietin mimetics on human megakaryocytes derived from patients
affected by inherited thrombocytopenias and healthy controls. In Aim 3 we will conduct studies to assess the
functionality of the platelets released in the bioreactor systems in vitro and in vivo. The outcome of these
studies is expected to be unprecedented insight into mechanisms that control platelet formation. These
insights will build on our ability to generate functional human platelets ex vivo but with significant
improvements in cell sources, disease insight and functional assessments in this renewal proposal. The
development of a unified solution based on the proposed science and technologies will clarify the impact of
thrombopoietin mimetics on human megakaryocyte behaviour in terms of activation of intracellular signaling,
differentiation, interaction with the extracellular environment and platelet production, all with major
implications for human health. Importantly, the successful outcome of this project will provide researchers
with new specialized tools for predicting the efficacy and safety of new drugs to address megakaryocyte-
 related diseases. In addition, the results will provide an important next step towards clinically relevant sources
and supplies of functional human platelets for patient treatments.

## Key facts

- **NIH application ID:** 9994294
- **Project number:** 5R01EB016041-08
- **Recipient organization:** TUFTS UNIVERSITY MEDFORD
- **Principal Investigator:** ALESSANDRA BALDUINI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $347,420
- **Award type:** 5
- **Project period:** 2012-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9994294

## Citation

> US National Institutes of Health, RePORTER application 9994294, In vitro bioreactor system for platelet formation (5R01EB016041-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9994294. Licensed CC0.

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