Abstract
Cell therapies using adipose-derived stem cells (ADSCs) have been used to treat inflammatory bowel disease (IBD) in human and dog. We previously reported the CellSaic technique, which uses a recombinant scaffold to enhance the efficacy of cell therapy. To examine whether this technique can be applied to cell therapy for colitis, we evaluated the efficacy of CellSaic in colitis mouse models. Colitis mouse models were developed by administering dextran sulfate sodium (DSS) to C57BL/6 mice for 7 days. Then CellSaic comprising human/canine ADSCs (1.2 × 106 cells) or human/canine ADSCs only (1.2 × 106 cells) were administered to the mice. The body weights were measured, and the colon length measurements and histological evaluations were conducted at 7 days after administration. After in vitro culture of human ADSC (hADSC) CellSaic and hADSC spheroids in medium containing TNFα, the levels of the anti-inflammatory protein TSG-6 in each supernatant were measured. Furthermore, we conducted tumorigenicity and general toxicity tests of canine ADSC (cADSC) CellSaic in NOG mice for 8 weeks. In the colitis mouse models, the ADSC CellSaic group presented recovery of body weight and colon length compared with the ADSC-only group. Histological analysis showed that ADSC CellSaic decreased the number of inflammatory cells and repaired ulceration. In vitro, hADSC CellSaic secreted 3.1-fold more TSG-6 than the hADSCs. In addition, tumorigenicity and general toxicity of cADSC CellSaic were not observed. This study suggests that human and canine ADSC CellSaic has a therapeutic effect of colitis in human and dogs.
Highlights
Human and veterinary therapies are considered to be integrated
We examined the anti-inflammatory effects of human ADSC (hADSC) CellSaic using a dextran sulfate sodium (DSS)-induced model of colitis
Non-DSS group [no treatment with DSS, n 1⁄4 5], DSS group [no cell transplantation into DSS mice, n 1⁄4 5], hADSC suspension i.p. group [1.2 Â 106 hADSCs in suspension intraperitoneally administered to DSS mice, n 1⁄4 5], hADSC CellSaic i.p. group [CellSaics of 1.2 Â 106 hADSCs and 1 mg u-pieces, intraperitoneally administered to DSS mice, n 1⁄4 5]. *p < 0.05. hADSC CellSaic group compared with DSS group and hADSC suspension group
Summary
Human and veterinary therapies are considered to be integrated. Physicians, and other scientific health and environmental professionals has been promoted in an initiative known as “One Health,” which is meant to improve the lives of all species by integrating human and veterinary medicine[1]. The role of veterinary patients in the evolution of stem cell therapies for both human and animal patients will be explored[2,3,4,5]. Stem cell therapies for both human and animals have been studied for regenerative medicine, mainly adipose-derived stem cells (ADSCs) and bone marrow mesenchymal stem cells (BMSCs). There are numerous reports of cell therapies using ADSCs and BMSCs in humans[6,7,8]. Reported results from a blinded, controlled trial in dogs with chronic osteoarthritis of the coxofemoral joint demonstrated efficacy of a single intraarticular injection of autologous ADSC therapy[10]
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