Hyo Jun Park

Anakinra Protects Against Serum Deprivation‐Induced Inflammation and Functional Derangement in Islets Isolated From Nonhuman Primates

We investigated whether serum deprivation induces islet amyloid polypeptide (IAPP) oligomer accumulation and/or a proinflammatory response and, if so, whether the addition of interleukin (IL)‐1 receptor antagonist to the culture medium can relieve the proinflammatory response during serum‐deprived culture of nonhuman primate (NHP) islets. After culture in medium with and without Ana under serum‐deprived culture conditions, IAPP oligomer/amyloid accumulation, in vitro viability, islet function, cytokine secretion, and posttransplantation outcome in streptozotocin‐induced diabetic nude mice were determined in islets isolated from heterozygote human IAPP transgenic (hIAPP+/−) mice and/or NHP islets. Serum deprivation induced accumulation of IAPP oligomer, but not amyloid, in NHP islets. Anakinra (Ana) protected islets from the serum deprivation–induced impairment of in vitro viability and glucose‐stimulated insulin secretion and attenuated serum deprivation–induced caspase‐1 activation, transcription, and secretion of IL‐1β, IL‐6, and tumor necrosis factor‐α in hIAPP+/− mice and NHP islets. Supplementation of medium with Ana during serum‐deprived culture also improved posttransplantation in vivo outcomes of NHP islets. In conclusion, serum deprivation induced accumulation of IAPP oligomers and proinflammatory responses in cultured isolated islets. Supplementation of the culture medium with Ana attenuated the functional impairment and proinflammatory responses induced by serum deprivation in ex vivo culture of NHP islets.

Clinicopathologic analysis of undifferentiated carcinoma of the gallbladder

Undifferentiated carcinoma (UC) of the gallbladder (GB) is a rare malignant neoplasm and there have only been sparse case reports without precise description. We analyzed eight cases of UC of GB and compared with gallbladder carcinoma (GBC) in the aspects of clinicopathologic characteristics and prognosis.

Highly Angiogenic, Non-Thrombogenic Bone Marrow Mononuclear Cells–Derived Spheroids in Intraportal Islet Transplantation

Highly angiogenic bone marrow mononuclear cell–derived spheroids (BM-spheroids), formed by selective proliferation of the CD31+CD14+CD34+ monocyte subset via three-dimensional (3D) culture, have had robust angiogenetic capacity in rodent syngeneic renal subcapsular islet transplantation. We wondered whether the efficacy of BM-spheroids could be demonstrated in clinically relevant intraportal islet transplantation models without increasing the risk of portal thrombosis. The thrombogenic potential of intraportally infused BM-spheroids was compared with that of mesenchymal stem cells (MSCs) and MSC-derived spheroids (MSC-spheroids). The angiogenic efficacy and persistence in portal sinusoids of BM-spheroids were examined in rodent syngeneic and primate allogeneic intraportal islet transplantation models. In contrast to MSCs and MSC-spheroids, intraportal infusion of BM-spheroids did not evoke portal thrombosis. BM-spheroids had robust angiogenetic capacity in both the rodent and primate intraportal islet transplantation models and improved posttransplant glycemic outcomes. MRI and intravital microscopy findings revealed the persistence of intraportally infused BM-spheroids in portal sinusoids. Intraportal cotransplantation of allogeneic islets with autologous BM-spheroids in nonhuman primates further confirmed the clinical feasibility of this approach. In conclusion, cotransplantation of BM-spheroids enhances intraportal islet transplantation outcome without portal thrombosis in mice and nonhuman primates. Generating BM-spheroids by 3D culture prevented the rapid migration and disappearance of intraportally infused therapeutic cells.