Intravenous injection of mesenchymal stem cell spheroids for efficient
pulmonary delivery and prolonged in vivo survival
Abstract
Because of their excellent therapeutic potential, mesenchymal stem cells
(MSCs) have been used as cell therapeutics for various diseases.
However, the survival rate and duration of MSCs after transplantation
are extremely low and short, respectively. To solve these problems, in
this study, we prepared multicellular spheroids of MSCs and investigated
their survival and function after intravenous injection in mice. The
murine adipose-derived MSC line m17.ASC was cultured in agarose-based
microwell plates to obtain size-controlled m17.ASC spheroids of an
average diameter and cell number of approximately 170 μm and 1100
cells/spheroid, respectively. The intravenously injected m17.ASC
spheroids mainly accumulated in the lung and showed a higher survival
rate than suspended m17.ASC cells during the experimental period of 7
days. m17.ASC spheroids efficiently reduced the
lipopolysaccharide-induced increase in plasma concentrations of
interleukin-6 and tumor necrosis factor-α. These results indicate that
spheroid formation improved the pulmonary delivery and survival of MSCs,
as well as their therapeutic potential against inflammatory pulmonary
diseases.