Effects of Human Adipose Tissue-Derived and Umbilical Cord Tissue-Derived Mesenchymal Stem Cells in a Dextran Sulfate Sodium-Induced Mouse Model.

Shunzo Ikarashi,Katsuyuki Oki,Shuji Terai,Yuzo Kawata,Maky Ideta-Otsuka,Yuichi Kojima,Suguru Takeuchi,Katsuhide Igarashi,Atsunori Tsuchiya,Masaaki Takamura,Takayuki Watanabe

doi:10.1089/biores.2019.0022

Abstract

Mesenchymal stem cells (MSCs) can be acquired from medical waste. MSCs are easily expanded and have multiple functions, including anti-inflammatory effects. We evaluated the effects of human adipose tissue-derived MSCs (AD-MSCs) and umbilical cord tissue-derived MSCs (UC-MSCs) in a dextran sulfate sodium (DSS)-induced mouse model. Human AD-MSCs and UC-MSCs (1 × 106 cells) were injected intravenously into a 7-day DSS-induced colitis model. The therapeutic effects of cell origin, injection timing, and supernatants obtained from MSC cultures were evaluated. We also analyzed messenger RNA (mRNA) expression in MSCs, tissues, and intestinal flora. AD-MSCs and UC-MSCs were found to show strong anti-inflammatory effects when injected on day 3 in a mouse model. On day 11, the mRNA levels of inflammatory factors in colon tissues were significantly decreased after injection of MSCs on day 3. Supernatants from MSCs culture decreased mRNA levels of tumor necrosis factor (Tnf)-α, but had reduced therapeutic effects compared with MSC cell injection. RNA sequencing using colon tissues obtained the day after cell injection revealed changes in the TNF-α/nuclear factor-κB and T cell receptor signaling pathways. Additional analyses showed that several factors, including chromosome 10 open reading frame 54, stanniocalcin-1, and TNF receptor superfamily member 11b were increased in MSCs after adding serum from DSS colitis mice. Furthermore, both AD-MSCs and UC-MSCs maintained the balance of intestinal flora. In conclusion, AD-MSCs and UC-MSCs showed therapeutic effects against inflammation after early cell injection while maintaining the intestinal flora. Although supernatants showed therapeutic effects, cell injection was more effective against inflammation.

Highlights

Inflammatory bowel diseases (IBDs) comprise chronic inflammatory disorders and include ulcerative colitis (UC) and Crohn’s disease (CD)
Early timing of AD-Mesenchymal stem cells (MSCs) and umbilical cord tissue-derived MSCs (UC-MSCs) injection ameliorated dextran sulfate sodium (DSS)-induced colitis To confirm the therapeutic effects of human ADMSCs and UC-MSCs in DSS-induced colitis and determine the appropriate injection timing, human adipose tissue-derived MSCs (AD-MSCs) and UC-MSCs were injected on day 3 or 7 into mice with DSS-induced colitis, and the therapeutic effects were analyzed on days 11 and 21 after DSS induction
No differences in therapeutic effects between AD-MSCs and UC-MSCs were detected for disease activity index (DAI), colon length, and histological score

Summary

Introduction

Inflammatory bowel diseases (IBDs) comprise chronic inflammatory disorders and include ulcerative colitis (UC) and Crohn’s disease (CD). The pathogenesis of IBDs is highly complex and involves abnormal immune reactions caused by environmental factors, intestinal antigens and bacteria, and diet; the underlying mechanisms are still not completely understood.[1,2] The mechanisms of inflammation have been extensively analyzed, and multiple potential therapeutic targets have been identified. Therapy is focused on control of inflammation and mucosal healing rather than complete cure of the disease.

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