Localized hydrogel delivery of dendritic cells for attenuation of multiple sclerosis in a murine model

Thomas, Adrian; Beskid, Nicholas M.; Blanchfield, Lori; Rosado, Aaron M.; Garcı́a, Andrés J.; Evavold, Brian D; Babensee, Julia E.

doi:10.1002/jbm.a.37118

Cited by 16 publications

(15 citation statements)

References 61 publications

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“…More CD11b + APCs and CD11c + dendritic cells were present in the LN and CNS of EAE mice than the control group. Furthermore, the costimulatory molecule CD86 is a well-established marker of activation for APCs and dendritic cells [ 67 , 68 ] whose expression increases with progression of disease in EAE [ 69 ]. More recently, CD4 + /IL17a + T-cells have been shown to be important primers of EAE, enhancing the severity of disease [ 70 ].…”

Section: Discussionmentioning

confidence: 99%

CEST MRI and MALDI imaging reveal metabolic alterations in the cervical lymph nodes of EAE mice

Thomas

Yang

Smith

et al. 2022

J Neuroinflammation

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Background Multiple sclerosis (MS) is a neurodegenerative disease, wherein aberrant immune cells target myelin-ensheathed nerves. Conventional magnetic resonance imaging (MRI) can be performed to monitor damage to the central nervous system that results from previous inflammation; however, these imaging biomarkers are not necessarily indicative of active, progressive stages of the disease. The immune cells responsible for MS are first activated and sensitized to myelin in lymph nodes (LNs). Here, we present a new strategy for monitoring active disease activity in MS, chemical exchange saturation transfer (CEST) MRI of LNs. Methods and results We studied the potential utility of conventional (T2-weighted) and CEST MRI to monitor changes in these LNs during disease progression in an experimental autoimmune encephalomyelitis (EAE) model. We found CEST signal changes corresponded temporally with disease activity. CEST signals at the 3.2 ppm frequency during the active stage of EAE correlated significantly with the cellular (flow cytometry) and metabolic (mass spectrometry imaging) composition of the LNs, as well as immune cell infiltration into brain and spinal cord tissue. Correlating primary metabolites as identified by matrix-assisted laser desorption/ionization (MALDI) imaging included alanine, lactate, leucine, malate, and phenylalanine. Conclusions Taken together, we demonstrate the utility of CEST MRI signal changes in superficial cervical LNs as a complementary imaging biomarker for monitoring disease activity in MS. CEST MRI biomarkers corresponded to disease activity, correlated with immune activation (surface markers, antigen-stimulated proliferation), and correlated with LN metabolite levels.

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Section: Discussionmentioning

confidence: 99%

CEST MRI and MALDI imaging reveal metabolic alterations in the cervical lymph nodes of EAE mice

Thomas

Yang

Smith

et al. 2022

J Neuroinflammation

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“…As such, studies aimed to modulate the inflammatory role of dendritic cells to instead inhibit immune activity. These cells were then encapsulated in PEG hydrogels and injected into murine MS models, with results displaying prolonged survival of the mice and reduced onset of paralysis [ 81 ].…”

Section: Mechanics Of Microencapsulationmentioning

confidence: 99%

Microencapsulation-based cell therapies

Marikar

El‐Osta

Johnston

et al. 2022

Cell. Mol. Life Sci.

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Mapping a new therapeutic route can be fraught with challenges, but recent developments in the preparation and properties of small particles combined with significant improvements to tried and tested techniques offer refined cell targeting with tremendous translational potential. Regenerating new cells through the use of compounds that regulate epigenetic pathways represents an attractive approach that is gaining increased attention for the treatment of several diseases including Type 1 Diabetes and cardiomyopathy. However, cells that have been regenerated using epigenetic agents will still encounter immunological barriers as well as limitations associated with their longevity and potency during transplantation. Strategies aimed at protecting these epigenetically regenerated cells from the host immune response include microencapsulation. Microencapsulation can provide new solutions for the treatment of many diseases. In particular, it offers an advantageous method of administering therapeutic materials and molecules that cannot be substituted by pharmacological substances. Promising clinical findings have shown the potential beneficial use of microencapsulation for islet transplantation as well as for cardiac, hepatic, and neuronal repair. For the treatment of diseases such as type I diabetes that requires insulin release regulated by the patient's metabolic needs, microencapsulation may be the most effective therapeutic strategy. However, new materials need to be developed, so that transplanted encapsulated cells are able to survive for longer periods in the host. In this article, we discuss microencapsulation strategies and chart recent progress in nanomedicine that offers new potential for this area in the future.

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“…Moreover, Thomas et al developed a poly(ethylene glycol) (PEG)-based hydrogel for local transplantation of IL-10-treated DCs. 78 The DC-containing hydrogel could reprogram the immune microenvironment of the injection site, realizing prevention from the progression of sclerosis.…”

Section: Biomaterial-assisted Cell Therapiesmentioning

confidence: 99%