Metabolically engineered stem cell-derived exosomes to regulate macrophage heterogeneity in rheumatoid arthritis

Despite the remarkable advances in therapeutics for rheumatoid arthritis (RA), a large number of patients still lack effective countermeasures. Recently, the reprogramming of macrophages to an immunoregulatory phenotype has emerged as a promising therapeutic strategy for RA. Here, we report metaboli...

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Bibliographic Details
Published in:Science advances 2021-06, Vol.7 (23)
Main Authors: You, Dong Gil, Lim, Gyeong Taek, Kwon, Seunglee, Um, Wooram, Oh, Byeong Hoon, Song, Seok Ho, Lee, Jungmi, Jo, Dong-Gyu, Cho, Yong Woo, Park, Jae Hyung
Format: Article
Language:English
Subjects:
Animals
Arthritis, Experimental - therapy
Arthritis, Rheumatoid - drug therapy
Cell Biology
Exosomes
Humans
Life Sciences
Macrophages
Mice
SciAdv r-articles
Stem Cells
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Summary:Despite the remarkable advances in therapeutics for rheumatoid arthritis (RA), a large number of patients still lack effective countermeasures. Recently, the reprogramming of macrophages to an immunoregulatory phenotype has emerged as a promising therapeutic strategy for RA. Here, we report metabolically engineered exosomes that have been surface-modified for the targeted reprogramming of macrophages. Qualified exosomes were readily harvested from metabolically engineered stem cells by tangential flow filtration at a high yield while maintaining their innate immunomodulatory components. When systemically administered into mice with collagen-induced arthritis, these exosomes effectively accumulated in the inflamed joints, inducing a cascade of anti-inflammatory events via macrophage phenotype regulation. The level of therapeutic efficacy obtained with bare exosomes was achievable with the engineered exosomes of 10 times less dose. On the basis of the boosted nature to reprogram the synovial microenvironment, the engineered exosomes display considerable potential to be developed as a next-generation drug for RA.
ISSN:2375-2548
2375-2548
DOI:10.1126/sciadv.abe0083