Pig islets are an alternative source for islet transplantation to treat type 1 diabetes (T1D), but reproducible curative potential in the pig-to-nonhuman primate (NHP) model has not been demonstrated. Here, we report that pig islet grafts survived and maintained normoglycemia for >6 months in four of five consecutive immunosuppressed NHPs. Pig islets were isolated from designated pathogen-free (DPF) miniature pigs and infused intraportally into streptozotocin-induced diabetic rhesus monkeys under pretreatment with cobra venom factor (CVF), anti-thymocyte globulin (ATG) induction and maintenance with anti-CD154 monoclonal antibody and low-dose sirolimus. Ex vivo expanded autologous regulatory T cells were adoptively transferred in three recipients. Blood glucose levels were promptly normalized in all five monkeys and normoglycemia (90-110 mg/dL) was maintained for >6 months in four cases, the longest currently up to 603 days. Intravenous glucose tolerance tests during the follow-up period showed excellent glucose disposal capacity and porcine C-peptide responses. Adoptive transfer of autologous regulatory T cells was likely to be associated with more stable and durable normoglycemia. Importantly, the recipients showed no serious adverse effects. Taken together, our results confirm the clinical feasibility of pig islet transplantation to treat T1D patients without the need for excessive immunosuppressive therapy.
The above results suggest that TXA₂ and cysteinyl leukotrienes, other than leukotriene D₄, are endogenous factors that facilitate HPV in rats. The indispensable role of TXA₂-induced pretone in the HPV of isolated pulmonary arteries indicates that the signal from thromboxane receptors might be a critical component of oxygen sensation mechanisms.
A simplified cochlear implant (CI) system would be appropriate for widespread use in developing countries. Here, we describe a CI that we have designed to realize such a concept. The system implements 8 channels of processing and stimulation using the continuous interleaved sampling (CIS) strategy. A generic digital signal processing (DSP) chip is used for the processing, and the filtering functions are performed with a fast Fourier transform (FFT) of a microphone or other input. Data derived from the processing are transmitted through an inductive link using pulse width modulation (PWM) encoding and amplitude shift keying (ASK) modulation. The same link is used in the reverse direction for backward telemetry of electrode and system information. A custom receiver-stimulator chip has been developed that demodulates incoming data using pulse counting and produces charge balanced biphasic pulses at 1000 pulses/s/electrode. This chip is encased in a titanium package that is hermetically sealed using a simple but effective method. A low cost metal-silicon hybrid mold has been developed for fabricating an intracochlear electrode array with 16 ball-shaped stimulating contacts.
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