Improved control over MSCs behavior within 3D matrices by using different cell loads in both in vitro and in vivo environments

Int J Pharm. 2017 Nov 25;533(1):62-72. doi: 10.1016/j.ijpharm.2017.09.014. Epub 2017 Sep 8.


The combination of multipotent mesenchymal stromal cells (MSCs) and different biomaterials has led to enormous advances in cell-based therapies, among which cell microencapsulation technologies are included. In the present work, we have studied the influence of different cell densities on the behavior of erythropoietin (EPO)-secreting MSCs immobilized in alginate microcapsules for their use as drug delivery systems. In vitro studies showed a more sustained and controlled EPO-secretion in groups with higher cell densities, which may be related to a more balanced renewal of the encapsulated cells, while low and intermediate densities gave rise to a continuous increase of both the number of cells and the EPO secretion levels. However, in vivo studies depicted a completely different scenario. Here the higher levels of cell proliferation led to a rapid space saturation and oxygen depletion of the capsule core, which eventually resulted in implant failure for the highest cell loads. On the contrary, lower cell densities showed a longer lasting release with a steadily increasing secretion profile. In conclusion, these results demonstrate how the final outcome of a cell-based drug delivery system may be tuned by just modifying the initial cell load, always taking into account the surrounding microenvironment.

Keywords: Cell microencapsulation; D1 multipotent mesenchymal stromal cells (D1-MSCs); Drug delivery; Erythropoietin; In vivo; Sustained release.

MeSH terms

  • Alginates / chemistry
  • Animals
  • Capsules
  • Cell Proliferation
  • Cell Survival
  • Drug Delivery Systems*
  • Erythropoietin / administration & dosage*
  • Female
  • Glucuronic Acid / chemistry
  • Hexuronic Acids / chemistry
  • Mesenchymal Stem Cells*
  • Mice, Inbred C57BL


  • Alginates
  • Capsules
  • EPO protein, human
  • Hexuronic Acids
  • Erythropoietin
  • Glucuronic Acid