title: Preparation and characterization of directed, one-day-self-assembled millimeter-size spheroids of adipose-derived mesenchymal stem cells.
abstract: Three-dimensional cell spheroids prepared without using any artificial scaffold materials are desirable for cell-based transplants. However, conventional cell culture systems are inefficient for rapid, large-scale and non-cytotoxic generation of size-controlled spheroids (>1 mm diameter) that are required for tissue regenerative therapy application. In this study, we prepared millimeter-order spheroids of adipose-derived mesenchymal stem cells (ADSCs) by controlling the spheroid size (diameter range: 0.4-2.5 mm). Notably, spheroid generation required only one day of culture on charged culture dishes. Almost all spheroid-derived ADSCs were viable and produced adhesion molecules and growth factors, which play an important role in tissue regeneration. Moreover, spheroid-derived ADSCs could infiltrate and recellularize collagenous tissue membranes in vitro. The ADSC spheroids developed in this study could be directly (without additional processing) used for cell-based tissue regeneration therapy. Furthermore, the rapid scale-up process and noncytotoxic generation of spheroids would also enable other applications such as use as screening models for drug discovery.
authors.affiliation: Division of Medical Engineering and Materials, National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Iwai
authors.affiliation: Development Department, Chemical Products Division, Bridgestone, Co, Yokohama, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Nemoto
authors.affiliation: Division of Medical Engineering and Materials, National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan.
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Nakayama
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D017209:Apoptosis; D048429:Cell Size; D020287:In Situ Nick-End Labeling; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D011917:Rats, Inbred Lew; D018874:Spheroids, Cellular / Q000166:cytology*
keywords: adipose-derived mesenchymal stem cells; multicellular spheroids; regenerative medicine; self-assembly; tissue engineering