# Engineered Neuroprotective Stem-Cell Exosomes for In Utero Spina Bifida Therapy

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2022 · $492,615

## Abstract

ABSTRACT
Myelomeningocele (MMC) is the most severe form of spina bifida (SB) and the most common congenital cause
of lifelong paralysis in the United States, where approximately four children are born daily with this devastating
disease. MMC results from the incomplete closure of the neural tube and absent overlying spine leaving the
spinal cord exposed to intrauterine mechanical and chemical trauma. This trauma results in lifelong paralysis,
bowel and bladder dysfunction, musculoskeletal deformities, and cognitive disabilities due to hindbrain
herniation. In utero surgical repair improves morbidity, but functional recovery is incomplete and the majority of
children are still unable to walk independently. We developed a treatment for MMC that augments the standard
of care, in utero MMC surgical repair, with placental mesenchymal stromal/stem cells (PMSCs). We found that
treatment with PMSCs, during in utero repair, prevents hind limb paralysis in the well-established fetal ovine
model of MMC, due to PMSC paracrine secretion of neuroprotective factors. However, we confirmed that PMSCs
did not engraft long-term and treated lambs developed severe kyphosis causing spinal cord compression and
tethering due to the lack of bone and adjacent paraspinal muscles, which is consistent with human MMC
musculoskeletal deformities. To meet this need for a long-lasting therapy for MMC, we explored the use of
bioengineered multifunctional combination scaffolds. Exosomes are extracellular vesicles that play significant
roles in cell-to cell communication. We confirmed that exosomes secreted by PMSCs (PMSC-exosomes) exert
significant neuroprotective functions, similar in magnitude to the live PMSCs from which they are derived. In this
study, we propose to develop an engineered hydrogel system that will allow for both local and sustained release
of PMSC-exosomes to the spinal cord, which in turn will provide sustained neuroprotection to treat MMC before
birth. In addition, we aim to increase the longevity of the in utero treatment by covering the defect with a
biomaterial-based bony scaffold to provide structural and functional support. We plan to optimize the
neuroprotective and regenerative functions of the bioscaffold using our well-established fetal rodent and rabbit
models of MMC. We will evaluate the final combination multifunctional bioscaffold product in our gold-standard
fetal ovine model of MMC. This therapeutic will be cell-free, off-the-shelf, and easy-to-use. If successful, this
novel approach will be used to treat MMC before birth, and due to its regenerative qualities, the treatment will
improve the quality of life of these patients, as well as significantly lower the healthcare costs associated with
the current treatment.

## Key facts

- **NIH application ID:** 10465174
- **Project number:** 5R01NS115860-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Diana Lee Farmer
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $492,615
- **Award type:** 5
- **Project period:** 2020-09-30 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10465174

## Citation

> US National Institutes of Health, RePORTER application 10465174, Engineered Neuroprotective Stem-Cell Exosomes for In Utero Spina Bifida Therapy (5R01NS115860-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10465174. Licensed CC0.

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