In the field of cell therapy for cardiovascular diseases, researchers see two main ways that the cells can provide benefits:
*As building blocks â€“ actually replacing dead cells in damaged tissues
*As nurses — supplying growth factors and other supportive signals, but not becoming part of damaged tissues
Tension between these two roles arises partly from the source of the cells.
Many clinical trials have used bone marrow-derived cells, and the benefits here appear to come mostly from the â€œparacrine” nurse function.Â A more ambitious approach is to use progenitor-type cells, which may have to come from iPS cells or cardiac stem cells isolated via biopsy-like procedures. These cells may have a better chance of actually becoming part of the damaged tissueâ€™s muscles or blood vessels, but they are more difficult to obtain and engineer.
A related concern: available evidence suggests introduced cells â€“ no matter if they are primarily serving as nurses or building blocks — donâ€™t survive or even stay in their target tissue for long.
Stem cell biologist Young-sup Yoon and colleagues recently published a paper in Biomaterials in which the authors use chitosan, a gel-like carbohydrate material obtainedÂ by processing crustacean shells, to aid in cell retention and survival. Ravi Bellamkonda’s lab at Georgia Tech contributed to theÂ paper.
More refinement of these approaches are necessary before clinical use, Â but it illustrates how engineered mixtures of progenitor cells and supportive materials are becoming increasingly sophisticated and complicated.
The chitosan gelÂ resemblesÂ the alginate material used to encapsulate cellsÂ by the Taylor lab.Â Yoon’s teamÂ wasÂ testing efficacy in a hindlimb ischemia model, in which a mouseâ€™s leg is deprived of blood. This situation is analogous to peripheral artery disease, and the readout of success is the ability of experimental treatments to regrow capillaries in the damaged leg.
The current paper builds a bridge between the nurse and building block approaches, because the researchers mix two complementary types of cells: an angiogenic one derived from bone marrow cells that expands existing blood vessels, and a vasculogenic one derived from embryonic stem cells that drives formation of new blood vessels.Â Note: embryonic stem cells were of mouse origin, not human.
On top of the chitosan and the two different types of cells, research associate Sangho Lee and colleagues added lipid microtubes that release the growth factor VEGF.Â Having all four elements together (two cell types, chitosan and VEGF) in a “patch” provided the highest benefit in terms of the number of capillaries per square millimeter. Still, the authors acknowledge in the discussion that they didnâ€™t see a synergistic benefit of mixing the two cell types.