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Author Notes:

Correspondence to: J. S. Temenoff, johnna.temenoff@bme.gatech.edu

The authors would like to acknowledge Dr. Tobias Miller and Dr. Yifeng Peng for assistance with heparin material synthesis and NMR characterization.

The human MSCs employed in these studies were provided by the Texas A&M Health Science Center College of Medicine Institute for Regenerative Medicine at Scott & White.

Subjects:

Research Funding:

This work was supported by an NSF DMR (1207045) grant awarded to JST and the GT BioMAT T32 grant (NIH T32EB006343) to ET.

Contract grant sponsor: NCRR of the NIH; contract grant number: P40RR017447

Contract grant sponsor: NSF DMR; contract grant number: 1207045

Contract grant sponsor: BioMAT T32; contract grant number: NIH T32EB006343

Keywords:

  • mesenchymal stem cells
  • heparin
  • chondrocytic differentiation
  • cell coatings
  • growth factors

Cell number and chondrogenesis in human mesenchymal stem cell aggregates is affected by the sulfation level of heparin used as a cell coating

Tools:

Journal Title:

Journal of Biomedical Materials Research Part A

Volume:

Volume 104, Number 7

Publisher:

, Pages 1817-1829

Type of Work:

Article | Post-print: After Peer Review

Abstract:

For particular cell-based therapies, it may be required to culture mesenchymal stem cell (MSC) aggregates with growth factors to promote cell proliferation and/or differentiation. Heparin, a negatively charged glycosaminoglycan (GAG) is known to play an important role in sequestration of positively charged growth factors and, when incorporated within cellular aggregates, could be used to promote local availability of growth factors. We have developed a heparin-based cell coating and we believe that the electrostatic interaction between native heparin and the positively charged growth factors will result in (1) higher cell number in response to fibroblast growth factor-2 (FGF-2) and 2) greater chondrogenic differentiation in response to transforming growth factor-β1 (TGF-β1), compared to a desulfated heparin coating. Results revealed that in the presence of FGF-2, by day 14, heparin-coated MSC aggregates increased in DNA content 8.5 ± 1.6 fold compared to day 1, which was greater than noncoated and desulfated heparin-coated aggregates. In contrast, when cultured in the presence of TGF-β1, by day 21, desulfated heparin-coated aggregates upregulated gene expression of collagen II by 86.5 ± 7.5 fold and collagen X by 37.1 ± 4.7 fold, which was higher than that recorded in the noncoated and heparin-coated aggregates. These observations indicate that this coating technology represents a versatile platform to design MSC culture systems with pairings of GAGs and growth factors that can be tailored to overcome specific challenges in scale-up and culture for MSC-based therapeutics.

Copyright information:

© 2016 Wiley Periodicals, Inc.

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