title: Supramolecular hydrogels for long-term bioengineered stem cell therapy.
abstract: Synthetic hydrogels have been extensively investigated as artificial extracellular matrices (ECMs) for tissue engineering in vitro and in vivo. Crucial challenges for such hydrogels are sustaining long-term cytocompatible encapsulation and providing appropriate cues at the right place and time for spatio-temporal control of the cells. Here, in situ supramolecularly assembled and modularly modified hydrogels for long-term engineered mesenchymal stem cell (eMSC) therapy are reported using cucurbit[6]uril-conjugated hyaluronic acid (CB[6]-HA), diaminohexane conjugated HA (DAH-HA), and drug-conjugated CB[6] (drug-CB[6]). The eMSCs producing enhanced green fluorescence protein (EGFP) remain alive and emit the fluorescence within CB[6]/DAH-HA hydrogels in mice for more than 60 d. Furthermore, the long-term expression of mutant interleukin-12 (IL-12M) by eMSCs within the supramolecular hydrogels results in effective inhibition of tumor growth with a significantly enhanced survival rate. Taken together, these findings confirm the feasibility of supramolecular HA hydrogels as 3D artificial ECMs for cell therapies and tissue engineering applications.
authors.affiliation: Department of Materials Science and Engineering, 77 Cheongam-ro, Nam-gu, Pohang, 790-784, Republic of Korea.
authors.forename: Junseok
authors.initials: J
authors.lastname: Yeom
authors.forename: Su Jin
authors.initials: SJ
authors.lastname: Kim
authors.forename: Hyuntae
authors.initials: H
authors.lastname: Jung
authors.forename: Hong
authors.initials: H
authors.lastname: Namkoong
authors.forename: Jeonga
authors.initials: J
authors.lastname: Yang
authors.forename: Byung Woo
authors.initials: BW
authors.lastname: Hwang
authors.forename: Kyunghoon
authors.initials: K
authors.lastname: Oh
authors.forename: Kimoon
authors.initials: K
authors.lastname: Kim
authors.forename: Young Chul
authors.initials: YC
authors.lastname: Sung
authors.forename: Sei Kwang
authors.initials: SK
authors.lastname: Hahn
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D057005:Bioengineering / Q000379:methods*; D002470:Cell Survival / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006820:Hyaluronic Acid / Q000494:pharmacology; D020100:Hydrogels / Q000494:pharmacology*; D020287:In Situ Nick-End Labeling; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000473:pathology; D066244:Proton Magnetic Resonance Spectroscopy; D017207:Rats, Sprague-Dawley; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D033581:Stem Cell Transplantation; D019076:Transgenes
chemical_list: D020100:Hydrogels; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D006820:Hyaluronic Acid
keywords: host-guest interaction; hyaluronic acid; stem cell therapy; supramolecular hydrogels; transgene expression