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A nanofibrous electrospun patch to maintain human mesenchymal cell stemness

Abstract

Mesenchymal stem cells (MSCs) have been extensively investigated in regenerative medicine because of their crucial role in tissue healing. For these properties, they are widely tested in clinical trials, usually injected in cell suspension or in combination with tridimensional scaffolds. However, scaffolds can largely affect the fates of MSCs, inducing a progressive loss of functionality overtime. The ideal scaffold must delay MSCs differentiation until paracrine signals from the host induce their change. Herein, we proposed a nanostructured electrospun gelatin patch as an appropriate environment where human MSCs (hMSCs) can adhere, proliferate, and maintain their stemness. This patch exhibited characteristics of a non-linear elastic material and withstood degradation up to 4 weeks. As compared to culture and expansion in 2D, hMSCs on the patch showed a similar degree of proliferation and better maintained their progenitor properties, as assessed by their superior differentiation capacity towards typical mesenchymal lineages (i.e. osteogenic and chondrogenic). Furthermore, immunohistochemical analysis and longitudinal non-invasive imaging of inflammatory response revealed no sign of foreign body reaction for 3 weeks. In summary, our results demonstrated that our biocompatible patch favored the maintenance of undifferentiated hMSCs for up to 21 days and is an ideal candidate for tridimensional delivery of hMSCs.

Graphical Abstract

The present work reports a nanostructured patch gelatin-based able to maintain in vitro hMSCs stemness features. Moreover, hMSCs were able to differentiate toward osteo- and chondrogenic lineages once induces by differentiative media, confirming the ability of this patch to support stem cells for a potential in vivo application. These attractive properties together with the low inflammatory response in vivo make this patch a promising platform in regenerative medicine.

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Acknowledgements

The authors acknowledge Ms. Nupur Basu for harvesting the cells used in this study and Dr. Junping You and Dr. Armando Torres for helping with the in vivo studies. We also acknowledge Mr. Christopher Candelari and Chih Hao Liu for helping with the mechanical testing. We thank Dr. J. Gu of the HMRI Microscopy-SEM/AFM core, and Dr. David Haviland, Director of the flow cytometry core. We also thank Ms. Megan Livingston for editing this document. The authors gratefully acknowledge funding support from the following sources: Brown Foundation (Project ID, 18130011), the Hearst Foundation (Project ID, 18130017), the Cullen Trust for Health Care Foundation (Project ID, 18130014), and the DoD USAMRMC (Project ID, W81XWH-15-1-0718).

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Correspondence to F. Taraballi or E. Tasciotti.

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Pandolfi, L., Furman, N.T., Wang, X. et al. A nanofibrous electrospun patch to maintain human mesenchymal cell stemness. J Mater Sci: Mater Med 28, 44 (2017). https://doi.org/10.1007/s10856-017-5856-0

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Keywords

  • ThermoFisher Scientific
  • HFIP
  • Multilineage Differentiation
  • Osteogenic Marker
  • Chondrogenic Lineage