SUMMARYCell death cluster in transplanted cells remains a critical obstacle for regeneration strategies. This study describes a novel platform for cell transplantation (CellSaic) consisting of human mesenchymal stem cells (hMSCs) and petaloid pieces of recombinant peptide (RCP), which can prevent cell death by arranging the cells in a mosaic. When hMSC CellSaics were subcutaneously implanted into NOD/SCID mice, hMSC CellSaics prevented cell death and accelerated angiogenesis in the graft, compared to the findings obtained on solely implanting cell spheroids. Additionally, we examined the application of CellSaic for subcutaneous cotransplantation of 200 rat islets with 2 9 10 5 hMSCs into diabetic mice. As the results of blood glucose levels at 1 M, the islet-only group was 398 AE 30 mg/dl and the islets with hMSCs group were 180 AE 65 mg/dl. On the other hand, the islets with hMSCs CellSaic group showed 129 AE 15 mg/dl and significantly improved glucose tolerance (P < 0.05). Additionally, we showed that the surface texture of the RCP petaloid pieces played an important role in graft survival and angiogenesis. It is anticipated that CellSaic will be used as a new platform for cell transplantation and tissue regeneration.
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.
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