Therapeutic potential of human adipose-derived stem/stromal cell microspheroids prepared by three-dimensional culture in non-cross-linked hyaluronic acid gel

Kazuhide Mineda, Jingwei Feng, Hisako Ishimine, Hitomi Takada, Kentaro Doi, Shinichiro Kuno, Kahori Kinoshita, Koji Kanayama, Harunosuke Kato, Takanobu Mashiko, Ichiro Hashimoto, Hideki Nakanishi, Akira Kurisaki, Kotaro Yoshimura

研究成果: Article査読

41 被引用数 (Scopus)

抄録

Three-dimensional culture of mesenchymal stem/stromal cells for spheroid formation is known to enhance their therapeutic potential for regenerative medicine. Spheroids were prepared by culturing humanadipose-derived stem/stromal cells (hASCs) in a non-cross-linked hyaluronic acid (HA) gel and comparedwith dissociated hASCs and hASC spheroids prepared using a nonadherent dish. Preliminary experiments indicated that a 4% HA gel was the most appropriate for forming hASC spheroids with a relatively consistent size (20–50 mm) within 48 hours. Prepared spheroids were positive for pluripotency markers (NANOG, OCT3/4, and SOX-2), and 40% of the cells were SSEA-3-positive, amarker of the multilineage differentiating stress enduring or Muse cell. In contrast with dissociated ASCs, increased secretion of cytokines such as hepatocyte growth factor was detected in ASC spheroids cultured under hypoxia. On microarray ASC spheroids showed upregulation of some pluripotency markers and downregulation of genes related to the mitotic cell cycle. After ischemia-reperfusion injury to the fat pad in SCID mice, local injection of hASC spheroids promoted tissue repair and reduced the final atrophy (1.6%) compared with that of dissociated hASCs (14.3%) or phosphate-buffered saline (20.3%). Part of the administered hASCs differentiated into vascular endothelial cells. ASC spheroids prepared in a HA gel contain undifferentiated cells with therapeutic potential to promote angiogenesis and tissue regeneration after damage.

本文言語English
ページ(範囲)1511-1522
ページ数12
ジャーナルStem Cells Translational Medicine
4
12
DOI
出版ステータスPublished - 12-2015

All Science Journal Classification (ASJC) codes

  • 発生生物学
  • 細胞生物学

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