Noninvasive quantitative evaluation of viable islet grafts using ¹¹¹In-exendin-4 SPECT/CT

Islet transplantation (IT) is an effective β-cell replacement therapy for patients with type 1 diabetes; however, the lack of methods to detect islet grafts and evaluate their β-cell mass (BCM) has limited the further optimization of IT protocols. Therefore, the development of noninvasive β-cell imaging is required. In this study, we investigated the utility of the ¹¹¹Indium-labeled exendin-4 probe {[Lys12(111In-BnDTPA-Ahx)] exendin-4} (¹¹¹In exendin-4) to evaluate islet graft BCM after intraportal IT. The probe was cultured with various numbers of isolated islets. Streptozotocin-induced diabetic mice were intraportally transplanted with 150 or 400 syngeneic islets. After a 6-week observation following IT, the ex-vivo liver graft uptake of ¹¹¹In-exendin-4 was compared with the liver insulin content. In addition, the in-vivo liver graft uptake of ¹¹¹In exendin-4 using SPECT/CT was compared with that of liver graft BCM measured by a histological method. As a result, probe accumulation was significantly correlated with islet numbers. The ex-vivo liver graft uptake in the 400-islet-transplanted group was significantly higher than that in the control and the 150-islet-transplanted groups, consistent with glycemic control and liver insulin content. In conclusion, in-vivo SPECT/CT displayed liver islet grafts, and uptakes were corroborated by histological liver BCM. ¹¹¹In-exendin-4 SPECT/CT can be used to visualize and evaluate liver islet grafts noninvasively after intraportal IT

Low Cell-Matrix Adhesion Reveals Two Subtypes of Human Pluripotent Stem Cells.

We show that a human pluripotent stem cell (hPSC) population cultured on a low-adhesion substrate developed two hPSC subtypes with different colony morphologies: flat and domed. Notably, the dome-like cells showed higher active proliferation capacity and increased several pluripotent genes' expression compared with the flat monolayer cells. We further demonstrated that cell-matrix adhesion mediates the interaction between cell morphology and expression of KLF4 and KLF5 through a serum response factor (SRF)-based regulatory double loop. Our results provide a mechanistic view on the coupling among adhesion, stem cell morphology, and pluripotency, shedding light on the critical role of cell-matrix adhesion in the induction and maintenance of hPSC

Low Cell-Matrix Adhesion Reveals Two Subtypes of Human Pluripotent Stem Cells.

We show that a human pluripotent stem cell (hPSC) population cultured on a low-adhesion substrate developed two hPSC subtypes with different colony morphologies: flat and domed. Notably, the dome-like cells showed higher active proliferation capacity and increased several pluripotent genes' expression compared with the flat monolayer cells. We further demonstrated that cell-matrix adhesion mediates the interaction between cell morphology and expression of KLF4 and KLF5 through a serum response factor (SRF)-based regulatory double loop. Our results provide a mechanistic view on the coupling among adhesion, stem cell morphology, and pluripotency, shedding light on the critical role of cell-matrix adhesion in the induction and maintenance of hPSC

Effect of additional surgery after noncurative endoscopic submucosal dissection for early gastric cancer

Labor income indices are created for groupings of individuals, using data from the Panel Study of Income Dynamics. People are grouped by a clustering algorithm based on an estimated transition matrix between jobs, by education level, and by skill category. The groups are defined so that relatively few people move between them. For each of the groupings, we generate a labor income index using a hedonic repeated-measures regression methodology. Similarities between pairs of indices and between indices and individual labor incomes are described. It is argued that indices like those presented here might someday be used in settlement formulae in contracts promoting income risk management