The investigation of optimal transplantation site of insulin producing cell differentiated from adipose derived stem cell

Abstract

Background & Aim Background As a curative treatment for type 1 diabetes, we have established and reported a rapid and efficient protocol of insulin producing cell (IPC) differentiation from adipose derived stem cell (ADSC) which were isolated with a minimally invasive procurement (Wada Y, Ikemoto T, et al. Sci Rep. 2019). Experimental β cell transplantation is often performed under the kidney capsule in murine model, however this is not suitable for clinical application. Aim We examined the optimal transplantation site for clinical transplantation of IPCs. Methods, Results & Conclusion Methods ADSCs were differentiated into IPC using our developed xeno-antigen free, 3D cultured (scaffold; cellnest, provided by Fuji Film CO.,Ltd) and two-step protocol which we have reported (Ikemoto T, et al. Sci Rep. 2019). BALB/c nu-nu mice were induced to a diabetic state with 200mg/kg streptozotocin as the recipients. 2.0 × 106 generated IPCs were transplanted in the mesenteric space (n=4), under the kidney capsule (n=4), and subcutaneous space (n=2), respectively. Non-fasting blood glucose and body weight were measured and observed in every 3 days. Immunohistochemical evaluations were undergone after the transplanted mice were sacrificed sequentially. Results Under the kidney capsule group, blood glucose level decreased below 200mg/dl on day 10 and then gradually reached the normal range (4/4, 100%). In the mesenteric space group, blood glucose level approached the normal range more quickly and normalized below 150mg/dl around day 14 (4/4,100%). In both groups blood glucose level was normalized with single shot of IPC transplantation. As a preliminary data, the tendency of improving hyperglycemic state was observed in subcutaneous space group, however, that improvement did not reach the significance. Conclusion The optimal site for IPC transplantation was considered to be in the mesenteric space from our investigations. Simultaneously, we plan to research the usefulness of subcutaneous transplantation with administration of angiogenetic factor, for achieving less invasive transplantation of IPCs.