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Biomimicking Robust Hydrogel for the Mesenchymal Stem Cell Carrier

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Abstract

Purpose

This study was aimed to develop a hydrogel-nanofiber as an advanced carrier for adipose derived human mesenchymal stem cells (AD-MSCs) and evaluate its potential for immunomodulatory therapies applicable to surface coating of drug eluting stent (DES) against coronary artery diseases (CAD).

Methods

A mixture of dispersing-nanofibers (dNFs) and poly (ethylene glycol)-diacrylate (PEGDA) were blended with sodium alginate to achieve robust mechanical strength. The effects of stem cell niche on cell viability and proliferation rates were evaluated using LDH assay and alamar blue assay, respectively. The amount of Nile-red microparticles (NR-MPs) remained in the hydrogel scaffolds was examined as an index for the physical strength of hydrogels. To evaluate the immunomodulatory activity of AD-MSCs as well as their influence by ROS, the level of L-Kynurenine was determined as tryptophan replacement compounds in parallel with IDO secreted from AD-MSCs using a colorimetric assay of L-amino acid.

Results

Both SA-cys-PEG and SA-cys-dNF-PEG upon being coated on stents using electrophoretic deposition technique displayed superior mechanical properties against the perfused flow. d-NFs had a significant impact on the stability of SA-cys-dNF-PEG, as evidenced by the substantial amount of NR-MPs remained in them. An enhanced subcellular level of ROS by spheroidal cluster yielded the high concentrations of L-Kynurenine (1.67 ± 0.6 μM without H2O2, 5.2 ± 1.14 μM with 50 μM of H2O2 and 8.8 ± 0.51 μM with 100 μM of H2O2), supporting the IDO-mediated tryptophan replacement process.

Conclusion

The “mud-and-straw” hydrogels are robust in mechanical property and can serve as an ideal niche for AD-MSCs with immunomodulatory effects.

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Abbreviations

d-NFs:

Dispersing-nanofibers

EPD:

Electrophoretic deposition

IDO:

Indoleamine 2,3-dioxygenase

NR-MPs:

Nile-red microparticles

ROS:

Reactive oxygen species

SA-cys:

Hydrogel scaffolds made of Cysteine-conjugated sodium alginate

SA-cys-dNF:

Hydrogel scaffolds made of SA-cys blended with dNFs

SA-cys-dNF-PEG:

Hydrogel scaffolds made of SA-cys cross-linked with dNFs and PEG-DA

SA-cys-PEG:

Hydrogel scaffolds made of SA-cys cross-linked with PEG-DA

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ACKNOWLEDGMENTS AND DISCLOSURES

This research was supported in part by funds provided from Graduate Studies Research Grant program, UMKC and Dean’s Bridge Fund program from School of Pharmacy, UMKC.

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Authors and Affiliations

  1. Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, Kansas City, Missouri, 64108, USA

    Byeongtaek Oh & Chi H. Lee

  2. Division of Pharmacology and Toxicology, School of Pharmacy, University of Missouri-Kansas City, Kansas City, Missouri, 64108, USA

    Russell B. Melchert

  3. Division of Pharmaceutical Sciences, University of Missouri at Kansas City, 2464 Charlotte Street, HSB-4242, Kansas City, Missouri, 64108, USA

    Chi H. Lee

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  1. Byeongtaek Oh
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Correspondence to Chi H. Lee.

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Oh, B., Melchert, R.B. & Lee, C.H. Biomimicking Robust Hydrogel for the Mesenchymal Stem Cell Carrier. Pharm Res 32, 3213–3227 (2015). https://doi.org/10.1007/s11095-015-1698-y

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  • DOI: https://doi.org/10.1007/s11095-015-1698-y

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