New Spotlight: Ultrasound-mediated spatial and temporal control of engineered cells in vivo.
Therapeutic cellular devices for intestinal inflammation.
Introduction
Development of new therapeutics for chronic inflammatory conditions remains a key focus of pre-clinical and clinical research. In a new publication, scientists from the University of Ljubljana show that an abdominally-implanted, ultrasound-activated cellular device can be used to deliver IL-10 local to the intestine, suppressing DSS-induced colitis. Similar, implanted cellular devices employing a genetic switch have been shown by others to promote cutaneous wound healing, through delivery of multiple growth factors. This new application of well-characterised, hollow fibre-encapsulated cell systems offers a new format for more tailored therapy of inflammatory conditions.
Main Points
- Anti-cytokine antibodies can be effective treatments for chronic inflammatory conditions such as IBD and RA; however, their strong systemic immunosuppressive effect means patients are at risk of infections and the activation of latent, cancer-causing viruses.
- Administration of anti-inflammatory cytokines (such as IL-10) is an alternative strategy, although these are expensive to manufacture and have short half-lives.
- Local delivery of active therapeutics is a desirable objective in attempting to refine clinical treatments and reduce unwanted systemic effects of drugs.
- Cellular devices offer the advantage of local implantation and the ability to deliver newly synthesised anti-inflammatory cytokines.
- Engineered, transcriptional regulation has previously been demonstrated to control delivery of a payload of growth factors to promote cutaneous wound healing [doi: 10.3389/fbioe.2023.1168330].
- In this Spotlight publication, the authors show the novel application of ultrasound to control the expression of IL-10 by an implanted cellular device.
- Ultrasound results in Ca2+ influx into the cytoplasm, via activation of mechanosensitive ion channels. This results in activation of the Ca2+/calmodulin signalling pathway and the translocation of the transcription factor, NFAT, to the nucleus. Cells used to make the cellular device are transfected with a plasmid encoding the Il10 gene under the control of an NFAT-dependent promoter.
Conclusion
This publication highlights the utility of a controllable cellular device for delivery of an effective anti-inflammatory therapy in vivo, demonstrating the potential for this therapeutic modality in the treatment chronic inflammatory conditions in humans.
EPISTEM SERVICES
Epistem offer a range of in vivo models of inflammatory bowel disease, which can be used to determine the efficacy of novel therapeutics. The models on offer include DSS-induced acute and chronic colitis, adoptive T cell transfer-mediated colitis and the IL-10 knockout model of spontaneous colitis.
Models of cutaneous wound healing are also available, including diabetes-impaired wound healing. These models are supported by a broad range of histological, biochemical and pharmacogenomic services.
