# Brain Recovery after Cardiac Arrest with Metabolic Glycoengineered Stem Cells

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 2020 · $337,969

## Abstract

Project Summary
Cardiac arrest (CA) has an incidence of 359,800 annually. Among survivors of CA, brain injury is the biggest
impediment to functional recovery. Currently, neither pharmacological intervention nor therapeutic
hypothermia can reverse the neural injury caused by CA. Stem cell therapy holds significant promise in the
neuronal repair after brain injury. However, poor viability and integration at the site of injury and lack of efficient
differentiation into the desired cell types hinder clinical applications. E
merging
metabolic glycoengineering
(MGE) technology by modification of surface glycans impacts cell adhesion and differentiation in vitro, however,
has not been investigated in the context of stem cell therapy. Therefore, the overall aim of this proposal is to
apply MGE to cell-based therapies to improve cell adhesion and viability after transplantation and enhance the
treatment efficacy to repair damaged neurons in ischemia brain after CA. The specific aims are:
 Aim1: With our novel MGE technique, we hypothesize that a novel glycan-based intervention is able to
promote human neural stem cell (hNSCs) neural differentiation and cell adhesion in vitro. We will develop and
optimize novel thiolated ManNAc analogs with longer alkyl chains, Ac5ManNPropT and Ac5ManNButT, that are
predicted to increase thiol accessibility and promote hNSCs cell adhesion and neural differentiation in vitro.
 Aim2: With optimized ManNAc analogs, we hypothesize that treated hNSCs will promote the survival,
distribution, and differentiation of transplanted hNSCs in vivo. We will evaluate the effect of glycoengineered
hNSCs on functional outcome after CA and optimize this cell-based therapy.
 Aim 3: With expected improvement in outcome after CA, we hypothesize that the success of the cell-
based intervention is due to improved survival and differentiation of transplanted glycoengineered hNSCs. We
will explore cellular interactions and molecular mechanisms after glycoengineered hNSC transplantation after
CA through Wnt/β-catenin signaling pathways.
The Significance lies in the combination of the MGE technique and stem cell therapy for repairing brain injury
post-CA, optimization of cell-based therapy towards clinical translation, and the expected discovery of the
mechanism underlying improved survival and differentiation after glycoengineered NSC transplantation. The
innovation lies in our innovative hypothesis to modify stem cell surface properties by MGE technology to
improve cell survival and differentiation, our novel and effective MGE method with low cost for modifying surface
glycans of hNSCs, and our use of the MGE technique in important disease in vivo model to develop novel
therapeutic cell-based intervention. Our study will lead to the development of novel therapeutic strategies to
repair brain injury towards future clinical interventions and maximize the benefits of MGE and stem cell therapy
based on the new findings. The use of sugar analog molecu...

## Key facts

- **NIH application ID:** 9979983
- **Project number:** 5R01NS110387-03
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Xiaofeng Jia
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $337,969
- **Award type:** 5
- **Project period:** 2018-09-30 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9979983

## Citation

> US National Institutes of Health, RePORTER application 9979983, Brain Recovery after Cardiac Arrest with Metabolic Glycoengineered Stem Cells (5R01NS110387-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9979983. Licensed CC0.

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