Generation of anti-inflammatory macrophages for implants and regenerative medicine using self-standing release systems with a phenotype-fixing cytokine cocktail formulation

Abstract

(2017) Generation of anti-inflammatory macrophages for implants and regenerative medicine using self-standing release systems with a phenotype-fixing cytokine cocktail formulation. Acta Biomaterialia . ISSN 1878-7568 Access from the University of Nottingham repository: http://eprints.nottingham.ac.uk/40797/1/2017%2001%2016_Ryabov_Acta %20Biomaterialia.pdf Copyright and reuse:The Nottingham ePrints service makes this work by researchers of the University of Nottingham available open access under the following conditions. This article is made available under the University of Nottingham End User licence and may be reused according to the conditions of the licence. For more details see: http://eprints.nottingham.ac.uk/end_user_agreement.pdf A note on versions:The version presented here may differ from the published version or from the version of record. If you wish to cite this item you are advised to consult the publisher's version. Please see the repository url above for details on accessing the published version and note that access may require a subscription.For more information, please contact eprints@nottingham.ac.uk facilitated wound closure by human fibroblasts in co-culture conditions. Using a model for induction of inflammation by LPS we have shown that the M2Ct phenotype is stable for 12 days. However, in the absence of M2Ct in the medium macrophages underwent rapid pro-inflammatory re-programming upon IFNg stimulation. Therefore, loading and release of the cytokine cocktail from a self-standing, transferable Gelatin/Tyraminated Hyaluronic acid based release system was developed to stabilize macrophage phenotype for in vivo application in implantation and tissue engineering. The M2Ct cytokine cocktail retained its anti-inflammatory activity in controlled release conditions. Our data indicate that the direct application of a potent M2 inducing cytokine cocktail in a transferable release system can significantly improve the long term functionality of biomedical devices by decreasing proinflammatory cytokine secretion and increasing the rate of wound healing.

Enforced microglial depletion and repopulation as a promising strategy for the treatment of neurological disorders

“…Considering that we have demonstrated the beneficial action of adoptively transferred immunomodulatory macrophages to prevent pathogenesis in settings of both Type 1 Diabetes (Parsa et al, ) and EAE (Zhang, Lund, Mia, Parsa, & Harris, ) and that other researchers have consequently successfully therapeutically employed our protocol in settings of spinal cord injury (Ma et al, ) and in wound healing (Riabov et al, ) then conceptually an initial transfer of immunomodulatory macrophages (either stimulated or gene‐modified) to halt the neuroinflammatory process could then be followed by transfer of microglia‐like cells. These approaches may provide a potential novel therapeutic angle for a wide array of neurological disorders and we currently actively explore this potential.…”

Macrophage and Fibroblast Interactions in Biomaterial‐Mediated Fibrosis

“…These results were correlated with significantly reduced number of macrophages and fibroblasts by 12 weeks, suggesting a role for TGF‐β1 in recruiting these cells or otherwise mediating their interactions with biomaterials . In another study, Riabov et al incorporated an M2‐stimulating cocktail of soluble factors (IL‐4, IL‐10, and TGF‐β1) into thin films of gelatin–hyaluronic acid–tyramine via spin coating . In an in vitro coculture of primary human macrophages and GFP‐labeled human lung fibroblasts (MRC5 cell line), the M2‐stimulating cocktail promoted fibroblast migration and increased MMP7 secretion in a scratch assay .…”

“…In another study, Riabov et al incorporated an M2‐stimulating cocktail of soluble factors (IL‐4, IL‐10, and TGF‐β1) into thin films of gelatin–hyaluronic acid–tyramine via spin coating . In an in vitro coculture of primary human macrophages and GFP‐labeled human lung fibroblasts (MRC5 cell line), the M2‐stimulating cocktail promoted fibroblast migration and increased MMP7 secretion in a scratch assay . In a monoculture of macrophages, sustained release of the M2‐stimulating cocktail promoted decreased secretion of proinflammatory cytokines TNF‐α, IL‐6, and IL‐1β, and increased secretion of the M2 marker (and profibrotic cytokine) CCL18 after 6 d in vitro …”

Parkinson's disease, aging and adult neurogenesis: Wnt/β‐catenin signalling as the key to unlock the mystery of endogenous brain repair

“…Micro/nanoparticulate delivery vehicles may be engineered to release multiple biomolecules with spatio‐temporal control are being developed, aimed at mobilizing NSCs efficiently from their niches to promote their engraftment at lesioned areas, or creating a long term anti‐inflammatory microenvironment (Li et al, ; Riabov et al, ; Tiwari et al, ; Zhang, Zhang, Deng, et al, ; Zhang, Shi, et al, ; Zhang, Zhang, Yang, et al, ; Zhang, Huang, et al, ). Curcumin‐loaded nanoparticles powerfully induce adult neurogenesis and reverse cognitive deficits in an Alzheimer's disease model via the activation of WβC‐signalling pathway (Tiwari et al, , ).…”