2. Academic Validation
  3. Metabolically engineered stem cell-derived exosomes to regulate macrophage heterogeneity in rheumatoid arthritis

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

  • Sci Adv. 2021 Jun 2;7(23):eabe0083. doi: 10.1126/sciadv.abe0083.
Dong Gil You 1,  Gyeong Taek Lim 1,  Seunglee Kwon 1,  Wooram Um 1,  Byeong Hoon Oh 1,  Seok Ho Song 1,  Jungmi Lee 1,  Dong-Gyu Jo 2 3 4,  Yong Woo Cho 4 5,  Jae Hyung Park 6 2 4
Affiliations

Affiliations

  • 1 School of Chemical Engineering, College of Engineering, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon 16419, Republic of Korea.
  • 2 Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon 16419, Republic of Korea.
  • 3 School of Pharmacy, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon 16419, Republic of Korea.
  • 4 ExoStemTech Inc., 55 Hanyangdaehak-ro, Sangnok-gu, Ansan 15588, Republic of Korea.
  • 5 Department of Chemical Engineering, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan 15588, Republic of Korea.
  • 6 School of Chemical Engineering, College of Engineering, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon 16419, Republic of Korea. jhpark1@skku.edu.
PMID: 34078596 DOI: 10.1126/sciadv.abe0083
Abstract

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.

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