4.5 Article

Localized hydrogel delivery of dendritic cells for attenuationof multiplesclerosis in a murine model

期刊

JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
卷 109, 期 7, 页码 1247-1255

出版社

WILEY
DOI: 10.1002/jbm.a.37118

关键词

dendritic cells; in situ gelling hydrogel; localized delivery; multiple sclerosis; transplantation

资金

  1. National Institute of Biomedical Imaging and Bioengineering [1 R21 EB019166-01A1]
  2. National Institute of Diabetes and Digestive and Kidney Diseases [1 T90 DK097787, 1 R90 DK098981]
  3. National Institutes of Health [UL1TR000454]
  4. Georgia Partner's Regenerative Medicine (REM) seed grant
  5. Georgia Immunoengineering Consortium's seed grant

向作者/读者索取更多资源

The study demonstrated that local delivery of DC10s modulates immune cell recruitment and attenuates disease progression in a preclinical model of MS.
In multiple sclerosis (MS), abnormally activated immune cells responsive to myelin proteins result in widespread damage throughout the central nervous system (CNS) and ultimately irreversible disability. Immunomodulation by delivering dendritic cells (DCs) utilizes a potent and rapid MS disease progression driver therapeutically. Here, we investigated delivering DCs for disease severity attenuation using an experimental autoimmune encephalomyelitis preclinical MS model. DCs treated with interleukin-10 (IL-10) (DC10s) were transplanted using in situ gelling poly(ethylene glycol)-based hydrogel for target site localization. DC delivery increased hydrogel longevity and altered the injection site recruited, endogenous immune cell profile within 2 days postinjection. Furthermore, hydrogel-mediated DC transplantation efficacy depended on the injection-site. DCs delivered to the neck local to MS-associated CNS-draining cervical lymph nodes attenuated paralysis, compared to untreated controls, while delivery to the flank did not alter paralysis severity. This study demonstrates that local delivery of DC10s modulates immune cell recruitment and attenuates disease progression in a preclinical model of MS.

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