Stem
cell transplantation is currently implemented clinically but
is limited by low retention and engraftment of transplanted cells
and the adverse effects of inflammation and immunoreaction when allogeneic
or xenogeneic cells are used. Here, we demonstrate the safety and
efficacy of encapsulating human cardiac stem cells (hCSCs) in thermosensitive
poly(N-isopropylacrylamine-co-acrylic
acid) or P(NIPAM-AA) nanogel in mouse and pig models of myocardial
infarction (MI). Unlike xenogeneic hCSCs injected in saline, injection
of nanogel-encapsulated hCSCs does not elicit systemic inflammation
or local T cell infiltrations in immunocompetent mice. In mice and
pigs with acute MI, injection of encapsulated hCSCs preserves cardiac
function and reduces scar sizes, whereas injection of hCSCs in saline
has an adverse effect on heart healing. In conclusion, thermosensitive
nanogels can be used as a stem cell carrier: the porous and convoluted
inner structure allows nutrient, oxygen, and secretion diffusion but
can prevent the stem cells from being attacked by immune cells.