# Novel immunosuppressive mechanism of human bone marrow mesenchymal stem cells in experimental Crohn's disease

> **NIH NIH K08** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2023 · $81,095

## Abstract

Abstract
Crohn’s disease (CD) is chronic intestinal inflammatory disease that affects more than 700,000 individuals in the
US and is becoming more common worldwide. The use of biologics such as anti-TNF and anti-adhesion molecule
medications has significantly improved the quality of life of CD patients, however biologics tend to lose efficacy
with time and have significant side effects. New cell based therapies that utilize the immunosuppressive capacity
of adult mesenchymal stem cells (MSC) for immune mediated diseases like CD are currently in clinical trials. A
cumulative body of data, including our own work shows that locally injected MSC are a promising therapy for
patients with perianal fistulae refractory to anti-TNF’s. However, systemic MSC therapy for luminal CD has lower
efficacy, which may be due to myriad reasons with many inadequately investigated. All the murine studies
performed demonstrate the benefit of MSC therapy in mouse models that require manipulation to develop
inflammation and are focused on treating large intestinal inflammation. Though, nearly two thirds of human CD
patients have small intestinal involvement. Thus, there is a critical need to study MSC therapy in disease relevant
and preclinical murine models of CD. In this study, we propose to study the SAMP-1/YitFc (SAMP) mouse for
treatment with human MSC (hMSC).The SAMP strain is a unique model that spontaneously develops CD-like
small intestinal (SI) inflammation which has impressive similarities to the human disease. My strong preliminary
data has shown that SAMP mice with established SI inflammation treated with one dose of bone marrow derived
human MSC (hMSC) had significantly lower inflammation and had mucosal healing. Therefore, our hypothesis
is that hMSC treat SI inflammation in SAMP mice by a mechanism involving the modulation of transcriptome of
host tissue to an anti-inflammatory and tissue regeneration pathway. I will test this hypothesis in 2 specific aims.
In specific aim 1, we will use the SAMP mice, our new SAMP medical recurrence model, novel techniques
including 3D stereomicroscopy (for mucosal healing) to test the subhypothesis that hMSC can treat, prevent SI
inflammation and determine the optimal route of hMSC administration. In addition, using a novel hMSC optimized
for immunosuppression, we will determine if we can enhance the treatment efficacy of MSC therapy. In aim 2,
using human and mouse MSCs transduced with triple reporter, state-of-the-art imaging techniques, laser capture
microdissection, single cell RNA sequencing of host cells and MSCs we will investigate the mechanism(s) of
healing in SAMP after treatment with MSC. Our preclinical experimental design that tests 1) treatment of
established disease, 2) maintenance of remission, 3) the optimal route of MSC administration, 4) use of
enhanced immunosuppressive hMSC 5) hMSC effect on mucosal healing, and 6) comparative biology approach
to understand the mechanism (s) of healing has high rele...

## Key facts

- **NIH application ID:** 10854071
- **Project number:** 3K08DK110421-06S2
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Maneesh Dave
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $81,095
- **Award type:** 3
- **Project period:** 2017-04-15 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10854071

## Citation

> US National Institutes of Health, RePORTER application 10854071, Novel immunosuppressive mechanism of human bone marrow mesenchymal stem cells in experimental Crohn's disease (3K08DK110421-06S2). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10854071. Licensed CC0.

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