# A microRNA-mediated approach towards generating functional hematopoietic stem cells from human pluripotent stem cells in vitro

> **NIH NIH R21** · CEDARS-SINAI MEDICAL CENTER · 2023 · $459,250

## Abstract

PROJECT SUMMARY
Producing transplantable hematopoietic stem cells (HSCs) in vitro could benefit thousands of patients currently
unable to receive treatment for hematological disorders. The long-term goal is to be able to generate clinically
viable HSCs in vitro from human pluripotent stem cells (PSCs). This achievement would revolutionize the way
numerous blood diseases could be treated, and could theoretically alleviate patients from having to wait to find
a bone marrow transplant ‘match’, since a well-established clinical roadmap already exists for the use of HSCs
in a therapeutic setting. Our central hypothesis is based on our strategic transcriptional profiling analysis of
genetically identical in vivo HSCs (functional) and in vitro-derived ‘pre-HSCs’ (not functional). By eliminating
genetic background as a source of variability, to identify the key molecular differences that underlie the functional
deficiencies present in in vitro-generated HSCs, we were able to discover novel differences in regulatory
pathways modulated by miRNAs. Guided by strong preliminary data, the overall objective of this application is
to modulate key miRNAs during in vitro differentiation to thus provide a novel approach to obtaining functional
HSCs from human PSCs. This objective will be pursued under two specific aims: (1) To identify miRNA changes
during human PSC-mediated hematopoietic differentiation. In this aim, key miRNA expression levels will be
analyzed during PSC-hematopoietic differentiation assays; and (2) To examine the potential of miRNAs to
influence hematopoietic potential in vitro and in vivo. In this aim, key miRNA expression levels will be modified
during PSC-hematopoietic differentiation assays, and analyzed for their ability to successfully generate fully
functional HSCs in vitro. It is our expectation that our strategic approach will have a positive translational impact
by examining a novel pathway to generate HSCs in vitro that leads to long-term hematopoietic transplantation
capability, while also providing a much-needed comprehensive dataset resource for the hematopoietic field as a
whole towards the successful derivation of clinically viable HSCs in vitro.

## Key facts

- **NIH application ID:** 10810589
- **Project number:** 1R21AG078872-01A1
- **Recipient organization:** CEDARS-SINAI MEDICAL CENTER
- **Principal Investigator:** Athanasia Panopoulos
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $459,250
- **Award type:** 1
- **Project period:** 2023-09-30 → 2025-09-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10810589

## Citation

> US National Institutes of Health, RePORTER application 10810589, A microRNA-mediated approach towards generating functional hematopoietic stem cells from human pluripotent stem cells in vitro (1R21AG078872-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10810589. Licensed CC0.

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