Therapeutic Evaluation of Mesenchymal Stem Cells in Chronic Gut Inflammation

Abstract

The overall objective of this proposal is to evaluate the therapeutic efficacy of human, bone marrow-derived mesenchymal stem cells (MSCs) in a well-characterized mouse model of inflammatory bowel disease (IBD). Shortly after my relocation from LSU Health Sciences Center (LSUHSC) to my current position at Texas Tech Health Sciences Center (TTUHSC), we encountered an unexpected problem with our mouse model of IBD. We found that the incidence of intestinal inflammation in these mice was only 30-40% compared to our 15 year historical incidence of ~85% we observed at LSUHSC. Following a year of investigations, we identified the problem and were successful in reestablishing the model with an incidence of >95%. Although these investigations significantly delayed the start of the studies outlined in Task 1, we were able to begin experiments to ascertain the immuno-suppressive activity of human MSCs in our new and improved mouse model of IBD. These studies are currently ongoing. In addition, we made substantial progress in developing a more immunologically-relevant in vitro system to assess suppressive activity and mechanisms of MSCs that more closely models the cellular and immunological interactions that are thought to occur in our mouse model of IBD in vivo. Furthermore, we present exciting new data demonstrating that activation of MSCs with pro-inflammatory cytokines that are known to be overproduced in mouse and human IBD, induces the dramatic up-regulation of several different immuno-suppressive mediators. Finally, we present new data that utilizes a novel, highly sensitive and quantitative method for simultaneously measuring the homing of human MSCs to several different mouse tissues during the development of chronic gut inflammation.

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Document Details

Document Type
Technical Report
Publication Date
Sep 01, 2014
Accession Number
ADA618230

Entities

People

  • Matthew Grisham

Organizations

  • Texas Tech University Health Sciences Center

Tags

DTIC Thesaurus Topics

  • Body Weight
  • Cells
  • Chronic Diseases
  • Colitis
  • Culture Techniques
  • Cytokines
  • Diseases And Disorders
  • Health Services
  • Inflammation
  • Lymphatic System
  • Lymphocytes
  • Microbiomes
  • Proteins
  • Stem Cells
  • Therapy

Fields of Study

  • Biology

Readers

  • Computational Modeling and Simulation
  • Immunology
  • Oncology (Cancer Research).

Technology Areas

  • Biotechnology
  • Biotechnology - Cancer Biotech