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한빛사논문
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Adv. Funct. Mater., Sep 12 2023, 33 (37) 2302232 | https://doi.org/10.1002/adfm.202302232
In-drop thermal cycling of microcrystal assembly for senescence control (MASC) with minimal variation in efficacy
Ryan C Miller 1, Jonghwi Lee 2, Young Jun Kim 3, Hee-Sun Han 4,5, Hyunjoon Kong 1,5
1Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
2Department of Chemical Engineering and Materials Science, Chung-Ang University, Seoul 06974, Korea.
3Environmental Safety Group, Korea Institute of Science and Technology-Europe, Saarbrucken 66123, Germany.
4Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
5Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
CORRESPONDING AUTHORS : Hee-Sun Han, Hyunjoon Kong
Abstract
The secretome from mesenchymal stem cells (MSCs) has recently gained attention for new therapeutics. However, clinical application requires
in vitro cell manufacturing to attain enough cells. Unfortunately, this process often drives MSCs into a senescent state that drastically changes cellular secretion activities. Antioxidants are used to reverse and prevent the propagation of senescence; however, their activity is short-lived. Polymer-stabilized crystallization of antioxidants has been shown to improve bioactivity, but the broad crystal size distribution (CSD) significantly increases the efficacy variation. Efforts were made to crystalize drugs in microdroplets to narrow the CSD, but the fraction of drops containing at least one crystal can be as low as 20%. To this end, this study demonstrates that in-drop thermal cycling of hyaluronic acid-modified antioxidant crystals, named microcrystal assembly for senescence control (MASC), can drive the fraction of microdrops containing crystals to >86% while achieving significantly narrower CSDs (13±3μm) than in bulk (35±11μm). Therefore, this approach considerably improves the practicality of CSD-control in drops. In addition to exhibiting uniform release, MASC made with antioxidizing N-acetylcysteine extended the release time by 40%. MASC further improves the restoration of reactive oxygen species homeostasis in MSCs, thus minimizing cellular senescence and preserving desired secretion activities. We propose that MASC is broadly useful to controlling senescence of a wide array of therapeutic cells during biomanufacturing.
논문정보
- Research article
- 2023년 09월 (BRIC 등록일 2023-11-23)
- 국내+국외 연구진
- 바이오·의료융합 > 바이오소재
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