SDF-1 preconditioned HPC scaffolds mobilize cartilage-derived progenitors and stimulate meniscal fibrocartilage repair in human explant tissue culture

ABSTRACT

Purpose: The purpose of this study was to characterize the influence of SDF-1 on cell migration/adhesion and temporal gene expression of human cartilage mesenchymal progenitor cells (C-PCs); and to utilize SDF-1 conditioned mesenchymal progenitors to stimulate reintegration of human meniscus fibrocartilage breaks.

Materials and Methods: Characterization of SDF-1-induced cell migration was achieved using hydroxypropyl cellulose (HPC) scaffolds pretreated with SDF-1. Fluorescence microscopy and cell counting were used to visualize and quantify the extent of cell migration into scaffolds, respectively. Relative mRNA expression analysis was used to characterize the temporal effects of SDF-1 on C-PCs. Tissue reintegration experiments were conducted using cylindrical human meniscal tissue punches, which were then placed back together with an HPC scaffold embedded with C-PCs. Tensile testing was used to evaluate the extent of tissue reintegration stimulated by human mesenchymal progenitors.

Results: C-PCs migrate into scaffolds in response to SDF-1 with the same efficiency as mesenchymal progenitors from human marrow (BM-MSCs). SDF-1 treatment of C-PCs did not significantly alter the expression of early and late stage chondrogenic differentiation genes. Scaffolds containing SDF-1 pre-conditioned C-PCs successfully adhered to fibrocartilage breaks and migrated from the scaffold into the tissue. Tensile testing demonstrated that SDF-1 preconditioned C-PCs stimulate reintegration of fibrocartilage tears.

Conclusion: C-PCs migrate in response to SDF-1. Exposure to SDF-1 does not significantly alter the unique mRNA profile of C-PCs that make them desirable for cartilaginous tissue repair applications. SDF-1 pretreated mesenchymal progenitors successfully disperse into injured tissues to help facilitate tissue reintegration.

KEYWORDS:

• Knee meniscus
• cartilage progenitor
• SDF-1
• fibrocartilage
• HPC scaffold

Acknowledgments

We would like to acknowledge Ms. Jenasis Ortega for her assistance with bench experiments. This research was funded in part by faculty startup funds provided to Dr. Jayasuriya by the Rhode Island Hospital Department of Orthopaedics; by a clinical translational research pilot funding awarded to Dr. Jayasuriya and Dr. Owens through Institutional Development Award Number NIH U54GM115677 from the National Institute of General Medical Sciences (NIGMS); by the Orthopaedic Research and Education Foundation (OREF); and by the Bioengineering Core of the COBRE for Skeletal Health and Repair 5P30-GM122732. We would further like to thank the Department of Orthopaedics for working with the lab to acquire the meniscus samples used in this study.

Disclosure statement

No potential conflict of interest was reported by the authors.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

This work was supported by the National Institutes of Health [5P30-GM122732,U54GM115677]; Orthopaedic Research and Education Foundation [MTF/OREF Biologics].