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Intravenous injection of mesenchymal stem cell spheroids for efficient pulmonary delivery and prolonged in vivo survival
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  • Yoshihiko Shimazawa,
  • Kosuke Kusamori,
  • Mari Tsujimura,
  • Kazunori Shimizu,
  • Satoshi Konishi,
  • Makiya Nishikawa
Yoshihiko Shimazawa
Tokyo University of Science - Noda Campus
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Kosuke Kusamori
Tokyo University of Science - Noda Campus
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Mari Tsujimura
Tokyo University of Science - Noda Campus
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Kazunori Shimizu
Nagoya University Graduate School of Engineering School of Engineering
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Satoshi Konishi
Ritsumeikan University College of Science and Engineering Graduate School of Science and Engineering
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Makiya Nishikawa
Tokyo University of Science - Noda Campus
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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.

Peer review status:IN REVISION

15 Mar 2021Submitted to Biotechnology Journal
16 Mar 2021Assigned to Editor
16 Mar 2021Submission Checks Completed
22 Mar 2021Reviewer(s) Assigned
01 Jun 2021Editorial Decision: Revise Major