The contribution of adult stem cells to cardiac repair is mostly ascribed to an indirect paracrine effect, rather
than to their actual engraftment and differentiation into new contractile and vascular cells. This effect consists in a direct
reduction of host cell death, promotion of neovascularization, and in a “bystander effect” on local inflammation. A number
of cytokines secreted by adult stem/progenitor cells has been proposed to be responsible for the consistent beneficial
effect reported in the early attempts to deliver different stem cell subsets to the injured myocardium.
Aiming to maximize their beneficial activity on the diseased myocardium, the genetic modification of adult stem cells to
enhance and/or control the secretion of specific cytokines would turn them into active drug delivery vectors.
On the other hand, engineering biocompatible scaffolds as to release paracrine factors could result in multiple advantages:
(1) achieve a local controlled release of the drug of interest, thus minimizing off-target effects, (2) enhance stem cell retention
in the injured area and (3) boost the beneficial paracrine effects exerted by adult stem cells on the host tissue.
In the present review, a critical overview of the state-of-the-art in the modification of stem cells and the functionalization
of biocompatible scaffolds to deliver beneficial soluble factors to the injured myocardium is offered.
Besides the number of concerns to be addressed before a clinical application can be foreseen for such concepts, this path
could translate into the generation of active scaffolds as smart cell and drug delivery systems for cardiac repair.