title: A novel suture-based method for efficient transplantation of stem cells.
abstract: Advances in regenerative medicine have improved the potential of using cellular therapy for treating several diseases. However, the effectiveness of new cellular therapies is largely limited by low cell engraftment and inadequate localization. To improve on these limitations, we developed a novel delivery mechanism using cell-seeded biological sutures. We demonstrate the ability of cell-seeded biological sutures to efficiently implant human mesenchymal stem cells (hMSCs) to specific regions within the beating heart; a tissue known to have low cell retention and engraftment shortly after delivery. Cell-seeded biological sutures were developed by bundling discrete microthreads extruded from extracellular matrix proteins, attaching a surgical needle to the bundle and seeding the bundle with hMSCs. During cell preparation, hMSCs were loaded with quantum dot nanoparticles for cell tracking within the myocardium. Each biological suture contained an average of 5903 ± 1966 hMSCs/cm suture length. Delivery efficiency was evaluated by comparing cell-seeded biological suture implantation with intramyocardial (IM) cell injections (10,000 hMSCs in 35 μL) into the left ventricle of normal, noninfarcted rat hearts after 1 h. Delivery efficiency of hMSCs by biological sutures (63.6 ± 10.6%) was significantly higher than IM injection (11.8 ± 6.2%; p < 0.05). Cell-tracking analysis indicated suture-delivered hMSCs were found throughout the thickness of the ventricular myocardium: along the entire length of the biological suture track, localizing closely with native myocardium. These results suggest cell-seeded biological sutures can deliver cells to the heart more efficiently than conventional methods, demonstrating an effective delivery method for implanting cells in soft tissue.
authors.affiliation: Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, Massachusetts 01609, USA.
authors.forename: Jacques P
authors.initials: JP
authors.lastname: Guyette
authors.forename: Michael
authors.initials: M
authors.lastname: Fakharzadeh
authors.forename: Evans J
authors.initials: EJ
authors.lastname: Burford
authors.forename: Ze-Wei
authors.initials: ZW
authors.lastname: Tao
authors.forename: George D
authors.initials: GD
authors.lastname: Pins
authors.forename: Marsha W
authors.initials: MW
authors.lastname: Rolle
authors.forename: Glenn R
authors.initials: GR
authors.lastname: Gaudette
mesh_terms: D000818:Animals; D006352:Heart Ventricles / Q000378:metabolism*; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation / Q000295:instrumentation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013537:Sutures; D014183:Transplantation, Heterologous