Introduction to a new cell transplantation platform via recombinant peptide petaloid pieces and its application to islet transplantation with mesenchymal stem cells

Abstract

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.

Petaloid recombinant peptide enhances in vitro cartilage formation by synovial mesenchymal stem cells

“…Scaffolds such as PLGA and alginate are known to promote cartilage formation, but these scaffolds have the disadvantages of releasing substances that are harmful to the living body and that induce degeneration of the degeneration . These issues regarding scaffold materials are difficult to overcome, but the use of petaloid RCP may provide a solution …”

“…They also examined the effect of petaloid RCP in a streptozotocin‐induced diabetic model of mice. In these mice, co‐transplantation of pancreatic islets with bone marrow MSCs improved the function of the islets, so a mixture of islets and an MSC suspension was injected subcutaneously with or without petaloid RCP. The inclusion of petaloid RCP improved the diabetic condition in the mice, as indicated by a decreased blood glucose level and improved glucose tolerance …”

“…This RCP is produced by yeast, so it poses no risk of infection from diseases such as bovine spongiform encephalopathy. The shape of the RCP pieces influences its effects, and the petaloid shape was chosen in this study for its ability to create spaces between cells when mixed with MSCs …”

“…This RCP is based on the alpha-1 sequence of human collagen type I and contains 12 Arg-Gly-Asp (RGD) motifs in a single molecule, which increases its cell-adhesion ability. 8,9 The collagen type 1 antigenic site has been removed from the RCP to reduce immunogenicity after transplantation. This RCP is produced by yeast, so it poses no risk of infection from diseases such as bovine spongiform encephalopathy.…”

“…The shape of the RCP pieces influences its effects, and the petaloid shape was chosen in this study for its ability to create spaces between cells when mixed with MSCs. 9 In this study, we examined the effect of addition of petaloid RCP on in vitro chondrogenesis by synovial MSCs. The effect was evaluated by determining the cartilage pellet weight and the amount of glycosaminoglycan and DNA per pellet.…”