Allogeneic guinea pig mesenchymal stem cells ameliorate neurological changes in experimental colitis

Stem Cell Research & Therapy

Kulmira Nurgali²  Samy Sakkal²  Richard Boyd¹  Sarah Miller²  Ainsley M. Robinson²  Rhian Stavely² 

[1] Department of Anatomy and Developmental Biology, Monash University, 19 Innovation Walk, Clayton 3800, Victoria, Australia;Centre for Chronic Disease, College of Health and Biomedicine, Western Centre for Health, Research and Education, Sunshine Hospital, 176 Furlong road, Melbourne 3021, Victoria, Australia

关键词: TGF-β;    Allogeneic;    Adipose tissue;    Bone marrow;    Guinea pig;    Neuroprotection;    Colitis;    Multipotent stromal cells;    Mesenchymal stem cells;    Enteric neuropathy;   

Others  :  1235183
DOI  :  10.1186/s13287-015-0254-3

 received in 2015-08-03, accepted in 2015-12-02,  发布年份 2015

【 摘 要 】

Background

The use of mesenchymal stem cells (MSCs) to treat inflammatory bowel disease (IBD) is of great interest because of their immunomodulatory properties. Damage to the enteric nervous system (ENS) is implicated in IBD pathophysiology and disease progression. The most commonly used model to study inflammation-induced changes to the ENS is 2,4,6-trinitrobenzene-sulfonate acid (TNBS)-induced colitis in guinea pigs; however, no studies using guinea pig MSCs in colitis have been performed. This study aims to isolate and characterise guinea pig MSCs and then test their therapeutic potential for the treatment of enteric neuropathy associated with intestinal inflammation.

Methods

MSCs from guinea pig bone marrow and adipose tissue were isolated and characterised in vitro. In in vivo experiments, guinea pigs received either TNBS for the induction of colitis or sham treatment by enema. MSCs were administered at a dose of 1 × 10 ⁶cells via enema 3 h after the induction of colitis. Colon tissues were collected 24 and 72 h after TNBS administration to assess the level of inflammation and damage to the ENS. The secretion of transforming growth factor-β1 (TGF-β1) was analysed in MSC conditioned medium by flow cytometry.

Results

Cells isolated from both sources were adherent to plastic, multipotent and expressed some human MSC surface markers. In vitro characterisation revealed distinct differences in growth kinetics, clonogenicity and cell morphology between MSC types. In an in vivo model of TNBS-induced colitis, guinea pig bone marrow MSCs were comparatively more efficacious than adipose tissue MSCs in attenuating weight loss, colonic tissue damage and leukocyte infiltration into the mucosa and myenteric plexus. MSCs from both sources were equally neuroprotective in the amelioration of enteric neuronal loss and changes to the neurochemical coding of neuronal subpopulations. MSCs from both sources secreted TGF-β1 which exerted neuroprotective effects in vitro.

Conclusions

This study is the first evaluating the functional capacity of guinea pig bone marrow and adipose tissue-derived MSCs and providing evidence of their neuroprotective value in an animal model of colitis. In vitro characteristics of MSCs cannot be extrapolated to their therapeutic efficacy. TGF-β1 released by both types of MSCs might have contributed to the attenuation of enteric neuropathy associated with colitis.

【 授权许可】

   
2015 Stavely et al.

【 图 表 】

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