Laboratory of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Chiba, Japan.
Department of Biomolecular Engineering, Graduate School of Engineering, Nagoya University, Nagoya, Aichi, Japan.
Biotechnol J. 2022 Jan;17(1):e2100137. doi: 10.1002/biot.202100137. Epub 2021 Oct 8.
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.
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.
由于具有出色的治疗潜力，间充质干细胞（MSCs）已被用作各种疾病的细胞治疗方法。然而，移植后 MSC 的存活率和持续时间非常低且短。为了解决这些问题，在本研究中，我们制备了 MSC 的细胞球，并研究了它们在小鼠体内静脉注射后的存活和功能。
将鼠脂肪来源的 MSC 系 m17.ASC 在琼脂糖基微井板中培养，以获得平均直径和细胞数分别约为 170μm 和 1100 个细胞/球的大小可控的 m17.ASC 细胞球。静脉注射的 m17.ASC 细胞球主要在肺中积累，并且在 7 天的实验期间比悬浮的 m17.ASC 细胞具有更高的存活率。m17.ASC 细胞球可有效降低脂多糖诱导的血浆白细胞介素-6 和肿瘤坏死因子-α浓度的增加。
这些结果表明，细胞球形成提高了 MSC 的肺递送和存活率，以及它们对炎症性肺部疾病的治疗潜力。
