Bone marrow mesenchymal stromal cells support regeneration of intestinal damage in a colitis mouse model, independent of their CXCR4 expression

Author:

Pervin Burcu12ORCID,Gizer Merve13ORCID,Şeker Mehmet Emin12ORCID,Erol Özgür Doğuş12ORCID,Gür Sema Nur12ORCID,Polat Ece Gizem12ORCID,Değirmenci Bahar4ORCID,Korkusuz Petek35ORCID,Aerts‐Kaya Fatima126ORCID

Affiliation:

1. Department of Stem Cell Sciences Hacettepe University Graduate School of Health Sciences Ankara Turkey

2. Hacettepe University Center for Stem Cell Research and Development (PediSTEM) Ankara Turkey

3. Micro‐Electro‐Mechanic Systems (MEMS) Center Middle East Technical University Ankara Turkey

4. Department of Molecular Biology and Genetics Bilkent University Ankara Turkey

5. Department of Histology and Embryology Hacettepe University Faculty of Medicine Ankara Turkey

6. Hacettepe University Experimental Animals Application and Research Center (HÜDHAM) Ankara Turkey

Abstract

AbstractInflammatory bowel disease (IBD) is characterized by a chronically dysregulated immune response in the gastrointestinal tract. Bone marrow multipotent mesenchymal stromal cells have an important immunomodulatory function and support regeneration of inflamed tissue by secretion of soluble factors as well as through direct local differentiation. CXCR4 is the receptor for CXCL12 (SDF‐1, stromal‐derived factor‐1) and has been shown to be the main chemokine receptor, required for homing of MSCs. Increased expression of CXCL12 by inflamed intestinal tissue causes constitutive inflammation by attracting lymphocytes but can also be used to direct MSCs to sites of injury/inflammation. Trypsin is typically used to dissociate MSCs into single‐cell suspensions but has also been shown to digest surface CXCR4. Here, we assessed the regenerative effects of CXCR4high and CXCR4low MSCs in an immune‐deficient mouse model of DSS‐induced colitis. We found that transplantation of MSCs resulted in clinical improvement and histological recovery of intestinal epithelium. In contrary to our expectations, the levels of CXCR4 on transplanted MSCs did not affect their regenerative supporting potential, indicating that paracrine effects of MSCs may be largely responsible for their regenerative/protective effects.

Publisher

Wiley

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