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

> **NIH NIH K08** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2021 · $162,189

## 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...

## Key facts

- **NIH application ID:** 10124379
- **Project number:** 5K08DK110421-06
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Maneesh Dave
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $162,189
- **Award type:** 5
- **Project period:** 2017-04-15 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10124379

## Citation

> US National Institutes of Health, RePORTER application 10124379, Novel immunosuppressive mechanism of human bone marrow mesenchymal stem cells in experimental Crohn’s disease (5K08DK110421-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10124379. Licensed CC0.

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