# Reprogrammed cell therapy for white matter restoration in aged brain ischemia

> **NIH VA I01** · VETERANS HEALTH ADMINISTRATION · 2020 · —

## Abstract

Abstract
Ischemia causes a massive loss of both oligodendrocytes and its progenitor cells (OPCs), the
only cells responsible for myelination in the CNS, leading to axonal damage and demyelination,
failure of nerve signal conduction, sensorimotor dysfunction, and cognitive impairments. Thus,
OPC replacement therapy is a critical prerequisite for WM restoration and brain repair,
especially for aged subjects who have more severe WMI and poor oligodendrocyte
proliferative capacity compared to young subjects. We have successfully reprogrammed
reactive astrocytes surrounding the infarct core into OPCs by forced overexpression of three
transcription factors in the ischemic brain. Reprogrammed OPCs can proliferate/differentiate
into mature oligodendrocytes, remyelinate axons, and improve neurological function after brain
ischemia. We further discovered that iOPCs increase neuronal survival and axonal outgrowth.
The central hypothesis to be tested is that in vivo reprogrammed oligodendrocytes
improve neurological function by enhancing white matter remodeling, including axonal
remyelination and axonal outgrowth. The following three Aims are proposed: 1)
Characterize the maturity of iOPCs and their role in improving neurological function after
brain ischemia in aged mice in both genders. 2) Investigate whether iOPCs restore WM
by enhancing axonal remyelination and stimulating axonal outgrowth after brain
ischemia. 3) Aim 3: Test whether local brain infusions of recombinant SOA can reprogram
reactive astrocytes into oligodendrocytes, restore WM, and improve neurological function after
brain ischemia. Our long-term goal is to develop novel and unique strategies for long term
recovery of white matter and neurological function.

## Key facts

- **NIH application ID:** 9815315
- **Project number:** 5I01BX003923-02
- **Recipient organization:** VETERANS HEALTH ADMINISTRATION
- **Principal Investigator:** GUODONG CAO
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2018-10-01 → 2022-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9815315

## Citation

> US National Institutes of Health, RePORTER application 9815315, Reprogrammed cell therapy for white matter restoration in aged brain ischemia (5I01BX003923-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9815315. Licensed CC0.

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