DELAYED THE ESRD PROGRESSION BY TRANSPLANTING 3D PRINTED OMENTAL PATCH

Abstract BACKGROUND AND AIMS Renal fibrosis is one of the pathological hallmarks of chronic kidney disease (CKD) that can further progress to end-stage renal diseases (ESRD). Haemodialysis and kidney transplantation are the only feasible treatments of ESRD. In this study, a new treatment with autologous omental tissue was assessed to delay the progression of renal fibrosis. The omental tissue, a fatty structure, has been widely used in surgical procedures due to its immunologic, angiogenic characteristics and anti-fibrotic factors that enhance tissue repairs, cell proliferation and regeneration in a damaged tissue. Finally, we hypothesized that 3D printed omental patch can prevent renal fibrosis and help regenerate the damaged kidney in the animal model. The 3D printing can print cells and extracellular matrix uniformly to promote cell survival and differentiation during transplantation. The printing also can adjust the patch stiffness, providing a suitable environment for kidney recovery. METHOD Animal models of CKD were randomly divided into four groups: (A) sham-operated, (B) sham-operated + omental patch, (C) unilateral ureteral obstruction (UUO)-operated (Control) and (D) UUO-operated + omental patch. Micronized omental tissue as bio-ink was 3D printed in the form of a regular patch deformation. Then, the 3D printed omental patch was transplanted subcapsular layer of the kidney. All of the patches used in those groups were transplanted after 3 days of modelling. Kidneys were assessed histologically [Masson's Trichrome (MT), Sirius Red], by immunohistochemistry (α-SMA), molecular work (Bulk RNA sequencing, western blot) after 2 weeks of transplantation. RESULTS Omental patch treated group has been shown histologically less tubulointerstitial fibrosis and tubule atrophy by MT, Sirius Red staining. Particularly, the TGF beta mRNA expression level of the 3D printed omental treated group was decreased in the kidney, whereas the HGF level was significantly increased. Also, in terms of western blotting, pro-inflammatory and renal fibrosis markers (TGF-b, α-SMA) were all decreased. Moreover, in bulk RNA sequencing, we confirmed that STAT 3 kidney repair pathway and TF-beta signalling. From all those assessments we suggest that the induction of myofibroblasts and collagen deposition are all inhibited in the omental patch treated kidney model. The autologous 3D omental patch can prevent tubular atrophy and decreased tubulointerstitial fibrosis and this further delays the progression of ESRD. CONCLUSION The study demonstrated that the omental patch delays fibrosis and repairs tubule structure in the damaged kidney by providing protective effects to kidney disease. These studies indicate the feasibility of the use of the autologous omental patch in chronic kidney disease therapeutic effects and new treatment of renal replacement therapy (RRT).