Mesenchymal stem cells and acellular products attenuate murine induced colitis
- PDF / 4,178,208 Bytes
- 11 Pages / 595.276 x 790.866 pts Page_size
- 85 Downloads / 196 Views
RESEARCH
Open Access
Mesenchymal stem cells and acellular products attenuate murine induced colitis Yan Li1†, Jessica Altemus2† and Amy L. Lightner1*
Abstract Background: Mesenchymal stem cells (MSCs) are a well-established immunomodulatory agent which can also promote tissue repair and regeneration. Recent studies have demonstrated MSCs as a novel therapeutic for inflammatory bowel disease (IBD), a chronic idiopathic inflammatory disorder of the gastrointestinal tract. However, the precise role of MSCs in regulating immune responses is controversial, and its significance in the pathogenesis remains IBD undefined. In addition, MSCs’ acellular product, extracellular vesicles (EVs), may also play an important role in the armamentarium of therapeutics, but how EVs compare to MSCs remains unknown due to the lack of side-by-side comparative investigation. We herein compared MSCs and MSC-derived EVs for the treatment of IBD using a DSS-induced colitis model. Methods: A DSS-induced colitis model was used. At day 4, mice received adipose-derived MSCs, MSC-derived EVs, or placebo. Weight loss, stool consistency, and hematochezia was charted. At day 8, murine colons were harvested, histologic analysis performed, and serum/tissue cytokine analysis conducted. Results: MSCs and EVs demonstrated equivalent immunosuppressive function in DSS-treated mice through decreased colonic lymphocyte infiltration and attenuated disease severity after both MSC and EV treatment. Furthermore, both MSCs and EVs have an equivalent ability to inhibit inflammation in the DSS colitis model by inhibiting JAK, JNK 1/2, and STAT3 signaling. Conclusions: These results suggest that (i) both MSCs and EVs are effective therapeutic candidates for a DSS-induced mouse colitis model, (ii) MSCs and EVs have similar immunosuppressive and anti-inflammatory functions, and (iii) EVs may present a novel future therapeutic for the treatment of IBD. Keywords: Mesenchymal stem cells, Extracellular vesicles, Inflammatory bowel disease, Murine colitis model, Therapy
Introduction Ulcerative colitis (UC) and Crohn’s disease (CD) are the two primary phenotypes of inflammatory bowel disease (IBD), a chronic idiopathic inflammatory disorder of the gastrointestinal tract [1–4]. Patients suffer from a remitting-relapsing disease course and are often initiated on immunomodulator and/or monoclonal antibodies to address their symptoms. However, monoclonal antibodies are limited by lack of * Correspondence: [email protected] † Yan Li and Jessica Altemus contributed equally to this work. 1 Department of Colorectal Surgery, Digestive Disease Surgical Institute, Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH 44195, USA Full list of author information is available at the end of the article
primary response [5–9], loss of secondary response [10, 11], and increased risk of serious opportunistic infections [12]. In addition, despite the advent of monoclonal antibodies with infliximab approval in 1998, up to 30% of UC patients and 80% of CD patients still require surgical resection t
Data Loading...
