A biodegradable, immunoprotective, dual nanoporous capsule for cell-based therapies

Zhang, Xulang; He, Hongyan; Yen, Chun-Wan; Ho, W.S. Winston; Lee, L. James

doi:10.1016/j.biomaterials.2008.07.032

Cited by 42 publications

(41 citation statements)

References 24 publications

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“…Capitalizing on this correlation between rewardrelated brain activities and dopamine levels in the blood, we have designed a synthetic dopamine sensor-effector device that interfaces with peripheral dopamine, remotely wires into rewardassociated behavior, and converts transient reward stimuli into a dose-dependent systemic expression response. When operating in implanted designer cells self-connecting to the peripheral circulation (34)(35)(36)(37)(38)(39) and insulated from the host immune system inside semipermeable microcapsules (27), the synthetic dopamine sensor-effector device functionally interfaced with reward-associated brain activities and successfully managed antihypertensive treatment in an animal model by coordinating expression of the clinically licensed atrial natriuretic protein. Synthetic interfaces between brain activities and peripheral circulation may enable therapeutic interventions to be programmed by the autonomic Wild-type mice implanted with microencapsulated HEK REWARD (2 × 10 6 cells/ mouse) were exposed to different reward conditions including food (syrup/ water mixtures), sexual arousal [treated male mice with (+) and without (−) female mouse company], and the addiction drug methamphetamine (MA) that was optionally coadministered with the ganglionic blocker pentolinium tartate (PT).…”

Section: Discussionmentioning

confidence: 99%

“…dopamine-triggered transgene expression in vivo, we implanted wild-type mice with HEK REWARD , microencapsulated into clinically licensed alginate-poly-L-lysine-alginate capsules with a molecular cutoff of 72 kDa (27) to insulate the sensor device from the mouse physiology and its immune system and treated the animals with injections of diverse concentrations of dopamine or the synthetic DRD1 agonist SKF-38393. The SEAP levels profiled in the bloodstream of treated animals confirmed triggerdose-dependent transgene expression in their peripheral circulation ( Fig.…”

Section: Dopamine-and Reward-based Transgene Expression In Wild-typementioning

confidence: 99%

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Reward-based hypertension control by a synthetic brain–dopamine interface

Rössger

Hamri

Fussenegger

2013

Proc. Natl. Acad. Sci. U.S.A.

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Synthetic biology has significantly advanced the design of synthetic trigger-controlled devices that can reprogram mammalian cells to interface with complex metabolic activities. In the brain, the neurotransmitter dopamine coordinates communication with target neurons via a set of dopamine receptors that control behavior associated with reward-driven learning. This dopamine transmission has recently been suggested to increase central sympathetic outflow, resulting in plasma dopamine levels that correlate with corresponding brain activities. By functionally rewiring the human dopamine receptor D1 (DRD1) via the second messenger cyclic adenosine monophosphate (cAMP) to synthetic promoters containing cAMP response element-binding protein 1 (CREB1)-specific cAMP-responsive operator modules, we have designed a synthetic dopamine-sensitive transcription controller that reversibly fine-tunes specific target gene expression at physiologically relevant brain-derived plasma dopamine levels. Following implantation of circuit-transgenic human cell lines insulated by semipermeable immunoprotective microcontainers into mice, the designer device interfaced with dopamine-specific brain activities and produced a systemic expression response when the animal's reward system was stimulated by food, sexual arousal, or addictive drugs. Reward-triggered brain activities were able to remotely program peripheral therapeutic implants to produce sufficient amounts of the atrial natriuretic peptide, which reduced the blood pressure of hypertensive mice to the normal physiologic range. Seamless control of therapeutic transgenes by subconscious behavior may provide opportunities for treatment strategies of the future.

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Section: Discussionmentioning

confidence: 99%

Section: Dopamine-and Reward-based Transgene Expression In Wild-typementioning

confidence: 99%

Reward-based hypertension control by a synthetic brain–dopamine interface

Rössger

Hamri

Fussenegger

2013

Proc. Natl. Acad. Sci. U.S.A.

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“…Finally, PEG is commonly used to cap (PEGylation) or coat other degradable polymers in order to convey steric stabilization limiting the interactions between the device and the host. This is especially important in preventing phagocytosis of particle-based delivery vehicles [287]. In dentistry, poly(ethylene glycol)-like coatings (PEG-like) are used on titanium dental implants for their antifouling activity.…”

Section: Synthetic Polyethersmentioning

confidence: 99%

Biodegradable polymers for dental tissue engineering and regeneration

Conte¹,

Riccitiello²,

Luise³

et al. 2017

Biodegradable Polymers: Recent Developments and New Perspectives

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“…The importance of hydrogel roughness was demonstrated for implanted rough poly(L-lysine) (PLL)/Alginate microcapsules and only smoothing the surface by adding poly(acrylic acid) completely abolished the tissue response (Bünger et al, 2003). In most cases, smooth round surfaces had the lowest fibrosis promoting effect (Zhang et al, 2008). The most commonly applied materials for microencapsulation are alginate (Lim et al, 1980), agarose (Iwata et al, 1992), PEG and poly(hydroxyethylmetacrylate-methyl methacrylate) (Dawson et al, 1987).…”

Section: Macro and Microencapsulationmentioning

confidence: 99%