Study demonstrates how the transplantation of autologous functional pancreatic islets grown in rats into diabetic mouse models restores glycemic control.
Researchers led by Hiromitsu Nakauchi (University of Tokyo, Japan) have provided proof-of-principle evidence of interspecies organogenesis and its therapeutic potential in a diabetic mouse model.
Nakahuchi has previously reported the generation of rat pancreata from rat pluripotent stem cells (PSCs) in mice through interspecies blastocyst complementation. The functional rat pancreata generated were however mouse-sized, resulting in an inability to obtain sufficient numbers of islets for transplantation to assess their therapeutic potential in a diabetic rat model.
This earlier work prompted the current study in which mouse pancreata were instead generated within rats. Using transcription activator-like effector nuclease technology, the group developed Pdx1-deficient rats which disabled pancreatogenesis within these models. Mouse-derived PSCs were then injected in to the rat Pdx1-knockout blastocysts, thus creating interspecies chimeras with rat-sized pancreata composed of mouse-PSC-derived cells.
To assess the therapeutic potential of these PSC-derived islets, 100 islets were then transplanted into mice with streptozotocin-induced diabetes. This led to the restoration of glycemic control in the diabetic mouse model for over 370 days in the absence of immunosuppression (excluding 5 days post-transplant).
These findings therefore highlight the future potential of generating organs derived from donor PSCs in a xenogenic environment and how their transplantation could be utilized for disease therapeutics such as diabetes.
Yamaguchi T, Sato H, Kato-Itoh M et al. Interspecies organogenesis generates autologous functional islets. Nature. 542, 191-196 (2017); Morris A. Xeno-created pancreata — the future of diabetes treatment? Nat. Rev. Endocrinol. doi:10.1038/nrendo.2017.14 (2017) (Epub ahead of print).