TY - JOUR
T1 - Therapeutic potential of human adipose-derived stem/stromal cell microspheroids prepared by three-dimensional culture in non-cross-linked hyaluronic acid gel
AU - Mineda, Kazuhide
AU - Feng, Jingwei
AU - Ishimine, Hisako
AU - Takada, Hitomi
AU - Doi, Kentaro
AU - Kuno, Shinichiro
AU - Kinoshita, Kahori
AU - Kanayama, Koji
AU - Kato, Harunosuke
AU - Mashiko, Takanobu
AU - Hashimoto, Ichiro
AU - Nakanishi, Hideki
AU - Kurisaki, Akira
AU - Yoshimura, Kotaro
N1 - Publisher Copyright:
© AlphaMed Press 2015.
PY - 2015/12
Y1 - 2015/12
N2 - 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.
AB - 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.
KW - Adipose-derived stem/stromal cells
KW - Angiogenesis
KW - Floating culture
KW - Ischemia-reperfusion injury
KW - Muse cells
KW - Non-cross-linked hyaluronic acid
KW - Spheroids
KW - Three-dimensional culture
KW - Vascular endothelial cells
KW - Wound healing
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UR - http://www.scopus.com/inward/citedby.url?scp=84949668117&partnerID=8YFLogxK
U2 - 10.5966/sctm.2015-0037
DO - 10.5966/sctm.2015-0037
M3 - Article
C2 - 26494781
AN - SCOPUS:84949668117
SN - 2157-6564
VL - 4
SP - 1511
EP - 1522
JO - Stem Cells Translational Medicine
JF - Stem Cells Translational Medicine
IS - 12
ER -