4.5 Article

Intravenous injection of mesenchymal stem cell spheroids improves the pulmonary delivery and prolongs in vivo survival

Journal

BIOTECHNOLOGY JOURNAL
Volume 17, Issue 1, Pages -

Publisher

WILEY-V C H VERLAG GMBH
DOI: 10.1002/biot.202100137

Keywords

biodistribution; cell transplantation; mesenchymal stem cells; micromolding technique; multicellular spheroids

Funding

  1. GSK Japan Research

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This study demonstrated that forming multicellular spheroids of MSCs improved their pulmonary delivery and survival after intravenous injection, as well as their therapeutic potential against inflammatory pulmonary diseases.
Background Because of the 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. Methods and Results 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 mu m 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-alpha. Conclusions These results indicate that spheroid formation improved the pulmonary delivery and survival of MSCs, as well as their therapeutic potential against inflammatory pulmonary diseases.

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