Improvement of the monitoring and biosafety of encapsulated cells using the SFGNESTGL triple reporter system

Catena, Raúl; Santos, Edorta; Orive, Gorka; Hernández, Rosa Marı́a; Pedraz, José Luís; Calvo, Alfonso

doi:10.1016/j.jconrel.2010.05.018

Cited by 30 publications

(19 citation statements)

References 34 publications

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“…Also, functional interconnection of recurrent behavioral activities with production and systemic delivery of protein therapeutics will likely foster gene-and cell-based treatment strategies that require seamless and self-sufficient drug dosing at regular intervals. With the advent of personalized medicine, it may now be foreseen that autologous designer cells that are implanted into humans inside vascularizing semipermeable microcontainers could be remote-controlled by brain activities to produce and systemically deliver protein therapeutics at the right time and dose (40)(41)(42)(43). Provided that such designer cell implants are scalable to the patients' needs and could be replaced by ambulant interventions at patient-compliant intervals when becoming fibrotic, such braininstructed peripheral designer cell implants could make the taking of pills in specified amounts and in precise doses a thing of the past (43)(44)(45)(46).…”

Section: Discussionmentioning

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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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%

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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“…In addition to confirming the implant location of encapsulated cells, imaging can be used to simultaneously confirm the viability and function of the entrapped cells. Adding reporter genes to enable bioluminescence and/or fluorescence imaging allows accurate non-invasive follow-up of the encapsulated cells, providing quantitative, real-time, live-imaging determination of those cells [28][29][30][31][32]. The biosafety of the implant may also be reinforced by including suicide genes that enable external inactivation of entrapped cells once the therapy is complete, if dosing changes are desired, or in the case of deleterious effects.…”

Section: Smart Delivery Systemsmentioning

confidence: 99%

“…The biosafety of the implant may also be reinforced by including suicide genes that enable external inactivation of entrapped cells once the therapy is complete, if dosing changes are desired, or in the case of deleterious effects. For instance, both suicide and reporter genes (e.g., TGL triple-fusion reporter gene-GFP, firefly luciferase, and Herpes Simplex virus type 1 thymidine kinase) have been incorporated into cell encapsulation systems to provide concurrent monitoring and inactivation of encapsulated cells in vivo [29,33].…”

Section: Smart Delivery Systemsmentioning

confidence: 99%

Cell encapsulation: technical and clinical advances

Orive

Santos

Poncelet

et al. 2015

Trends in Pharmacological Sciences

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157

101

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“…Moreover, cell death can be induced by administration of ganciclovir, in case therapy needs to be interrupted. This system may represent a step forward in the control and biosafety of cell-and genetherapy-based microencapsulation protocols (Catena et al, 2010). The development of novel therapeutic strategies for neurodegenerative and neurological diseases represents one of the biggest unmet medical needs today.…”

Section: Discussionmentioning

confidence: 99%