Summary
In type 1 diabetes, a renewable source of human pancreatic β cells, in particular from human induced pluripotent stem cell (hiPSC) origin, would greatly benefit cell therapy. Earlier work showed that pancreatic progenitors differentiated from human embryonic stem cells
in vitro
can further mature to become glucose responsive following macroencapsulation and transplantation in mice. Here we took a similar approach optimizing the generation of pancreatic progenitors from hiPSCs. This work demonstrates that hiPSCs differentiated to pancreatic endoderm
in vitro
can be efficiently and robustly generated under large-scale conditions. The hiPSC-derived pancreatic endoderm cells (HiPECs) can further differentiate into glucose-responsive islet-like cells following macroencapsulation and
in vivo
implantation. The HiPECs can protect mice from streptozotocin-induced hyperglycemia and maintain normal glucose homeostasis and equilibrated plasma glucose concentrations at levels similar to the human set point. These results further validate the potential use of hiPSC-derived islet cells for application in clinical settings.
The passive biomechanical behavior of blood vessels is generally modeled by a parallel arrangement of elastin and collagen, with collagen recruitment depending on vessel strain. We experimentally determined the collagen recruitment distribution using confocal microscopy. Digital images from sections of rabbit carotid artery under increasing circumferential stretch ratio were acquired. The straightness of the fibers was measured to compute the fraction of recruited fibers for each stretch ratio. The experimental distribution obtained was then used in the model proposed by Zulliger et al. This model is based on a strain energy function (SEF), which provides a constituentbased description of the wall mechanics. Using this model, a fit of the pressure-radius curve was then performed by using the experimental collagen recruitment distribution with the collagen elastic constant as a free fit parameter. The fit was good, but the value of the collagen elastic constant obtained was below values reported in the literature. A second fit of the pressure-radius curve was also performed, whereby the collagen distribution was left free to adapt while the collagen elastic constant was set to a physiological value. The differences between the experimental collagen engagement distribution and the distribution obtained when the collagen elastic constant was fixed were analyzed. Good qualitative agreement was found between the experimental distribution of collagen recruitment and the model. Some experimental limitations and modeling approximations remain. Nevertheless, experimental proof of progressive collagen recruitment was established, which validates the basic hypothesis of the model.
a b s t r a c tThe retention, diffusion and structural properties of 2-4 nm nanoporous alumina membranes were investigated in view of their integration as size-selective interface in a glucose sensor. These membranes exhibit remarkable glucose diffusion properties with only a 5-fold reduction compared to free diffusion in water. The retention of the glucose-binding protein (Concanavalin A), which is characterized by a hydrodynamic radius of only 3.3 nm, was almost complete during at least 35 days. This high selectivity was also confirmed by SEM picture analysis showing a highly uniform pore size distribution. Finally, the glucose sensor including a nanoporous membrane as size-selective interface was able to measure glucose levels in physiological solution during 25 days, which confirms that annealed alumina membranes are well suited for size-selective interface of biosensors.
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