The Spleen Is an Ideal Site for Inducing Transplanted Islet Graft Expansion in Mice.

Takeshi Itoh,Kenjiro Kumano,Shohta Kodama,Hiroyuki Takahashi,Hitomi Nishinakamura,Paolo Fiorina

doi:10.1371/journal.pone.0170899

Takeshi Itoh, Kenjiro Kumano + Show 4 more

Open Access

https://doi.org/10.1371/journal.pone.0170899

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Abstract

Alternative islet transplantation sites have the potential to reduce the marginal number of islets required to ameliorate hyperglycemia in recipients with diabetes. Previously, we reported that T cell leukemia homeobox 1 (Tlx1)+ stem cells in the spleen effectively regenerated into insulin-producing cells in the pancreas of non-obese diabetic mice with end-stage disease. Thus, we investigated the spleen as a potential alternative islet transplantation site. Streptozotocin-induced diabetic C57BL/6 mice received syngeneic islets into the portal vein (PV), beneath the kidney capsule (KC), or into the spleen (SP). The marginal number of islets by PV, KC, or SP was 200, 100, and 50, respectively. Some plasma inflammatory cytokine levels in the SP group were significantly lower than those of the PV group after receiving a marginal number of islets, indicating reduced inflammation in the SP group. Insulin contents were increased 280 days after islet transplantation compared with those immediately following transplantation (p<0.05). Additionally, Tlx1-related genes, including Rrm2b and Pla2g2d, were up-regulated, which indicates that islet grafts expanded in the spleen. The spleen is an ideal candidate for an alternative islet transplantation site because of the resulting reduced inflammation and expansion of the islet graft.

Highlights

We demonstrated that the spleen is an ideal transplantation site for reducing the number of islets required to ameliorate hyperglycemia in STZ-induced diabetic mice
These results suggest that the spleen is a candidate alternative islet transplantation site
We analyzed the marginal number of islets required to ameliorate hyperglycemia in STZ-induced diabetic recipient mice at three different transplant sites, the portal vein (PV), kidney capsule (KC), and SP

Summary

Introduction

We hypothesized that the spleen is an ideal site for inducing regeneration of transplanted islets, leading to a reduced number of islets required to ameliorate hyperglycemia in diabetic recipient mice. Results Marginal number of islets required to ameliorate hyperglycemia in STZ-induced diabetic recipient mice by syngeneic islet transplantation into three different transplant sites To ameliorate hyperglycemia in STZ-induced diabetic recipient mice by islet transplantation into the PV (n = 7) and beneath the KC (n = 6), 200 and 100 islets were required, respectively (Fig 1A).

Results

Conclusion