title: A Detailed Assessment of Varying Ejection Rate on Delivery Efficiency of Mesenchymal Stem Cells Using Narrow-Bore Needles.
abstract: As the number of clinical trials exploring cell therapy rises, a thorough understanding of the limits of cell delivery is essential. We used an extensive toolset comprising various standard and multiplex assays for the assessment of cell delivery postejection. Primary human mesenchymal stem cell (hMSC) suspensions were drawn up into 100-µl Hamilton syringes with 30- and 34-gauge needles attached, before being ejected at rates ranging from 10 to 300 µl/minute. Effects of ejection rate, including changes in viability, apoptosis, senescence, and other key aspects of cellular health, were evaluated. Ejections at slower flow rates resulted in a lower percentage of the cell dose being delivered, and apoptosis measurements of samples ejected at 10 µl/minute were significantly higher than control samples. Immunophenotyping also revealed significant downregulation of CD105 expression in samples ejected at 10 µl/minute (p < .05). Differentiation of ejected hMSCs was investigated using qualitative markers of adipogenesis, osteogenesis, and chondrogenesis, which revealed that slower ejection rates exerted a considerable effect upon the differentiation capacity of ejected cells, thereby possibly influencing the success of cell-based therapies. The findings of this study demonstrate that ejection rate has substantial impact on the percentage of cell dose delivered and cellular health postejection.
authors.affiliation: School of Pharmacy, Wolfson Centre for Stem Cells, Tissue Engineering, and Modelling, University of Nottingham, Nottingham, United Kingdom.
authors.forename: Mahetab H
authors.initials: MH
authors.lastname: Amer
authors.affiliation: School of Pharmacy, Wolfson Centre for Stem Cells, Tissue Engineering, and Modelling, University of Nottingham, Nottingham, United Kingdom.
authors.forename: Felicity R A J
authors.initials: FR
authors.lastname: Rose
authors.affiliation: School of Pharmacy, Wolfson Centre for Stem Cells, Tissue Engineering, and Modelling, University of Nottingham, Nottingham, United Kingdom.
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: White
authors.affiliation: School of Pharmacy, Wolfson Centre for Stem Cells, Tissue Engineering, and Modelling, University of Nottingham, Nottingham, United Kingdom kevin.shakesheff@nottingham.ac.uk.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Shakesheff
mesh_terms: D050156:Adipogenesis; D017209:Apoptosis / Q000235:genetics; D002454:Cell Differentiation; D049109:Cell Proliferation / Q000235:genetics; D002470:Cell Survival / Q000502:physiology; D064987:Cell- and Tissue-Based Therapy; D016922:Cellular Senescence / Q000502:physiology; D020219:Chondrogenesis; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D009339:Needles; D010012:Osteogenesis
keywords: Cell therapy; Differentiation; Mesenchymal stem cell injection; Mesenchymal stem cells; Needles
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