Diabetes mellitus is a glucose metabolism syndrome characterized by hyperglycemia and glucosuria affecting over 300 million people globally.1,2 Type 1 diabetes mellitus (T1DM) is an autoimmune disorder that accounts for 5% to 10% of all diabetes cases. T1DM results in the destruction of insulin-producing pancreatic islets of Langerhans leading to uncontrolled glucose homeostasis.3 As such, patients afflicted with T1DM require vigilant blood-glucose management and exogenous insulin administration. Islet transplantation (IT) has emerged as a therapeutic clinical treatment for subsets of patients with T1DM, largely owing to the success of the “Edmonton Protocol” by Shapiro and colleagues in 2000.4 In clinical IT, cadaveric donor islets are transplanted into the portal vein of the liver, where they subsequently embolize and become vascularized. Despite the clinical success of IT to date, numerous obstacles are associated with the procedure, including, but not limited to, acute islet loss as a result of the instant blood-mediated inflammatory reaction and procedural risks including portal vein thrombosis and bleeding.5,6 Additionally, transplantation into the hepatic portal vein limits the ability to image and retrieve donor islets. Bioluminescence imaging was reported for its application in the assessment of pancreatic islet transplanting in the liver and kidney.7 However, the quantitative interpretation of bioluminescence imaging was complicated and difficult due to the light intensity dependence on varying transfection efficiency of reporter gene inserted to islets, the size of islets, and the parameters used in imaging. As such, there has been an ongoing need to identify a clinically relevant, extra-hepatic transplant site. Such a site would need to be capable of supporting an adequate transplant mass while offering sufficient vascular networks providing oxygen and nutrients during revascularization, thus promoting islet engraftment and function.8 Moreover, alternative cellular sources, such as stem cell-derived insulin-producing cells, could be introduced as prospective clinical therapies for T1DM. An attractive option for the transplant of these cell sources is the subcutaneous space, which offers accessibility and retrievability, as well as the potential for biopsy and simple monitoring.6 Preclinical IT models investigating the utility of the subcutaneous space as an alternative site for IT have been explored through the use of permanent and temporary devices with varied success.9,10 Recently, the Shapiro laboratory established a subcutaneous deviceless (DL) transplant technique (with no need for a permanent encapsulation device) capable of restoring euglycemia in a murine IT model.10 In this pivotal study, a hollow nylon catheter was implanted subcutaneously to stimulate a controlled foreign-body response capable of inducing local angiogenesis, thus promoting islet engraftment. The catheter is then removed, and the islets are injected into the prevasculaturized subcutaneous site. This is in contrast to other approaches that sometimes use a porous or mesh bag to host the islets while protecting them against immune attack. Reversal of diabetes without a permanent encapsulation device or exogenous growth factors was demonstrated in Ref. 10. The formation of angiogenesis around and within the graft significantly contributed to successful islet engraftment, supplying a densely vascularized cellular graft-supporting matrix for nutrition and physical support.8 Inherently, the subcutaneous site is hypoxic, and islets engrafted into the unmodified subcutaneous site fail to routinely reverse diabetes.8 In addition to the histological assessment postgraft retrieval, a methodology to monitor such angiogenesis prior to and during islet engraftment is lacking.