# Cord Blood Graft Engineering to Improve Engraftment and Reduce GVHD

> **NIH NIH P01** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2021 · $532,046

## Abstract

PROJECT SUMMARY
Cord blood transplantation (CBT) has clear advantages over transplantation with bone marrow or
peripheral blood stem cells, but its wider use has been limited by the low dose of stem and
progenitor cells in CB units, leading to delays in engraftment and a substantial rate of engraftment
failure. During the past PO1 funding period, we developed a marrow-derived mesenchymal stromal
cell (MSC)-CB coculture system that allowed us to significantly accelerate the time to neutrophil and
platelet engraftment. This advance was paralleled by results showing that ex vivo cell-surface
fucosylation of CB, using the fucosyltransferase (FT)-6 enzyme with GDP-fucose can boost
engraftment by promoting CB homing to marrow. Thus, in Project 1, we now propose a revised
series of studies directed to our long-term goal: bringing the results of CBT in line with outcomes
being reported for G-CSF-mobilized peripheral blood progenitor cells (Aims 1 and 2). This effort will
test CBT based on the combination of MSC-expansion of CB cells followed by exofucosylation with
FT-7 a second fucosyltransferase that is more physiologic than FT-6 and could be even more
effective at enhancing engraftment in the marrow.
Additionally, graft-versus-host disease (GVHD) continues to restrict the utility of CBT, an issue we
did not address specifically during the past PO1 award. Rates of grade III-IV GVHD after CBT
range from 5% to 30%. In our patients, those with acute liver and gastrointestinal (GI) GVHD have
significantly benefited from MSC treatment. In a xenogenic GVHD model, we have observed that
fucosylated MSCs can enhance homing to sites of inflammation, resulting in a striking survival
benefit compared with the outcome of unmanipulated MSC treatment. We have also recently
observed that CB tissue-derived MSCs are logistically easier to obtain and expand much more
rapidly than marrow-derived MSCs. Thus we now propose to test whether CB tissue-derived,
fucosylated MSCs can be used to abrogate acute, steroid-refractory liver and/or GI GVHD (Aim 3).
The interactive potential of this project is considerable, for example, the clinical trial in Aim 1 will
likely stimulate collaborations with Project 2 (reconstitution of virus-specific CTLs), Project 3 (NK
cell recovery) and Project 4 (recovery of tumor-specific immunity). Finally, we would stress that
many of the findings from Project 1 will not be restricted to CBT, but could extend well beyond
times to engraftment to settings as diverse as GVHD and regenerative medicine.

## Key facts

- **NIH application ID:** 10247041
- **Project number:** 5P01CA148600-10
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** Elizabeth J Shpall
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $532,046
- **Award type:** 5
- **Project period:** 2011-09-22 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10247041

## Citation

> US National Institutes of Health, RePORTER application 10247041, Cord Blood Graft Engineering to Improve Engraftment and Reduce GVHD (5P01CA148600-10). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10247041. Licensed CC0.

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