Increased yield of gelatin coated therapeutic cells through cholesterol insertion

Kara A. Davis, Hsuan Peng, Lakshman Chelvarajan, Ahmed Abdel-Latif, Brad J. Berron

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Gelatin coatings are effective in increasing the retention of MSCs injected into the heart and minimizing the damage from acute myocardial infarction (AMI), but early studies suffered from low fractions of the MSCs coated with gelatin. Biotinylation of the MSC surface is a critical first step in the gelatin coating process, and in this study, we evaluated the use of biotinylated cholesterol “lipid insertion” anchors as a substitute for the covalent NHS-biotin anchors to the cell surface. Streptavidin-eosin molecules, where eosin is our photoinitiator, can then be bound to the cell surface through biotin-streptavidin affinity. The use of cholesterol anchors increased streptavidin density on the surface of MSCs further driving polymerization and allowing for an increased fraction of MSCs coated with gelatin (83%) when compared to NHS-biotin (52%). Additionally, the cholesterol anchors increased the uniformity of the coating on the MSC surface and supported greater numbers of coated MSCs even when the streptavidin density was slightly lower than that of an NHS-biotin anchoring strategy. Critically, this improvement in gelatin coating efficiency did not impact cytokine secretion and other critical MSC functions. Proper selection of the cholesterol anchor and the biotinylation conditions supports cellular function and densities of streptavidin on the MSC surface of up to ~105 streptavidin molecules/μm2. In all, these cholesterol anchors offer an effective path towards the formation of conformal coatings on the majority of MSCs to improve the retention of MSCs in the heart following AMI.

Original languageEnglish
Pages (from-to)326-335
Number of pages10
JournalJournal of Biomedical Materials Research - Part A
Volume109
Issue number3
DOIs
StatePublished - Mar 2021

Bibliographical note

Publisher Copyright:
© 2020 Wiley Periodicals, Inc.

Funding

This work was partially supported by R01 HL127682 and the National Science Foundation under Award CBET‐1351531. The project described was also supported by the NIH National Center for Advancing Translational Sciences through grant number TL1TR001997. Dr. Abdel‐Latif is supported by the NIH Grant R01 HL138488. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NSF or NIH.

FundersFunder number
National Science Foundation (NSF)CBET‐1351531
National Institutes of Health (NIH)R01 HL138488
National Center for Advancing Translational Sciences (NCATS)TL1TR001997

    Keywords

    • cell coating
    • cell surface engineering
    • cholesterol
    • lipid insertion
    • streptavidin density

    ASJC Scopus subject areas

    • Ceramics and Composites
    • Biomaterials
    • Biomedical Engineering
    • Metals and Alloys

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