# Enhancing Bone Marrow Transplantation With Highly Engraftable Hematopoietic Stem Cells

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2021 · $434,403

## Abstract

PROJECT SUMMARY/ABSTRACT
 The curative potential for hematopoietic stem cell (HSC) transplant has expanded with therapeutic
evidence in diseases as far ranging as diabetes, autoimmune diseases such as multiple sclerosis and
scleroderma, or non-malignant hematologic disorders such as sickle cell anemia and thalassemia. If HSC
transplantation, and hematopoietic gene therapy, are going to be primary methods of treating, or curing disease,
numerous deficiencies in the current approaches must be addressed. In the context of gene therapy, limitations
in HSC number and/or reductions in engraftment efficiency and true multi-lineage reconstitution reduce the
efficacy potential of many current clinical programs. There is a critical need to define the “rules” of HSC
engraftment during transplantation, which will then provide targets for therapeutic intervention on HSCs, or at
the very least define distinct release criteria for altered HSC products. This proposal will utilize a newly
discovered subset of highly engraftable hematopoietic stem cells (heHSCs) and a novel method to mobilize them
from the bone marrow niche. The first aim is to Identify the mechanism(s) governing high engraftment of HSCs
in competitive environments. This aim will use functional assays to determine what features make an heHSC
more competitive and molecular analysis to identify a target(s) that can then be exploited to enhance clinical
transplant. The second aim is to evaluate non-toxic conditioning regimens that utilize stem cell trafficking and
endothelial opening. These studies will explore non-toxic methods to achieve hematopoietic engraftment that do
not rely on radiation or chemotherapeutics. The advances accomplished in this proposal will enhance our
understanding of HSC heterogeneity, define potential therapeutic strategies to enhance stem cell engraftment,
and will provide a proof of concept for trafficking-based conditioning regimens for non-malignant stem cell
transplantation.

## Key facts

- **NIH application ID:** 10072071
- **Project number:** 5R01HL144752-03
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Jonathan George Hoggatt
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $434,403
- **Award type:** 5
- **Project period:** 2019-01-15 → 2021-03-01

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10072071

## Citation

> US National Institutes of Health, RePORTER application 10072071, Enhancing Bone Marrow Transplantation With Highly Engraftable Hematopoietic Stem Cells (5R01HL144752-03). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10072071. Licensed CC0.

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