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.
Keywords: adipose-derived mesenchymal stem cells; colitis; dextran sulfate sodium; inflammation; intestinal flora; tumor necrosis factor; umbilical cord-derived mesenchymal stem cells.
© Shunzo Ikarashi et al. 2019; Published by Mary Ann Liebert, Inc.