A biomaterials approach to influence stem cell fate in injectable cell-based therapies

Background: Numerous stem cell therapies use injection-based administration to deliver high-density cell preparations. However, cell retention rates as low as 1% have been observed within days of transplantation. This study investigated the effects of varying administration and formulation parameters of injection-based administration on cell dose recovery and differentiation fate choice of human mesenchymal stem cells. Methods: The impact of ejection rate via clinically relevant Hamilton micro-syringes and biomaterial-assisted delivery was investigated. Cell viability, the percentage of cell dose delivered as viable cells, proliferation capacity as well as differentiation behaviour in bipotential media were assessed. Characterisation of the biomaterial-based cell carriers was also carried out. Results: A significant improvement of in-vitro dose recovery in cells co-ejected with natural biomaterials was observed, with ejections within 2% (w/v) gelatin resulting in 87.5 +/- 14% of the cell dose being delivered as viable cells, compared to 32.2 +/- 19% of the dose ejected in the commonly used saline vehicle at 10 mu l/min. Improvement in cell recovery was not associated with the rheological properties of biomaterials utilised, as suggested by previous studies. The extent of osteogenic differentiation was shown to be substantially altered by choice of ejection rate and cell carrier, despite limited contact time with cells during ejection. Collagen type I and bone-derived extracellular matrix cell carriers yielded significant increases in mineralised matrix deposited at day 21 relative to PBS. Conclusions: An enhanced understanding of how administration protocols and biomaterials influence cell recovery, differentiation capacity and choice of fate will facilitate the development of improved administration and formulation approaches to achieve higher efficacy in stem cell transplantation.