An injectable non-cross-linked hyaluronic-acid gel containing therapeutic spheroids of human adipose-derived stem cells
Abstract For chronic wounds, the delivery of stem cells in spheroidal structures can enhance graft survival and stem cell potency. We describe an easy method for the 3D culture of adipose-derived stem/stromal cells (ASCs) to prepare a ready-to-use injectable. We transferred suspensions of monolayer-...
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Nature Portfolio
2017
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oai:doaj.org-article:9511dc0efc514fe0a0baef4c277d14dd2021-12-02T11:52:41ZAn injectable non-cross-linked hyaluronic-acid gel containing therapeutic spheroids of human adipose-derived stem cells10.1038/s41598-017-01528-32045-2322https://doaj.org/article/9511dc0efc514fe0a0baef4c277d14dd2017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01528-3https://doaj.org/toc/2045-2322Abstract For chronic wounds, the delivery of stem cells in spheroidal structures can enhance graft survival and stem cell potency. We describe an easy method for the 3D culture of adipose-derived stem/stromal cells (ASCs) to prepare a ready-to-use injectable. We transferred suspensions of monolayer-cultured ASCs to a syringe containing hyaluronic acid (HA) gel, and then incubated the syringe as a 3D culture vessel. Spheroids of cells formed after 12 h. We found that 6 × 106 ASCs/ml in 3% HA gel achieved the highest spheroid density with appropriate spheroid sizes (20–100 µm). Immunocytology revealed that the stem cell markers, NANOG, OCT3/4, SOX-2, and SSEA-3 were up-regulated in the ASC spheroids compared with those in nonadherent-dish spheroids or in monolayer cultured ASCs. In delayed wound healing mice models, diabetic ulcers treated with ASC spheroids demonstrated faster wound epithelialization with thicker dermis than those treated with vehicle alone or monolayer cultured ASCs. In irradiated skin ulcers in immunodeficient mice, ASC spheroids exhibited faster healing and outstanding angiogenic potential partly by direct differentiation into α-SMA+ pericytes. Our method of 3D in-syringe HA gel culture produced clinically relevant amounts of ready-to-inject human ASC microspheroids that exhibited superior stemness in vitro and therapeutic efficacy in pathological wound repair in vivo.Jingwei FengKazuhide MinedaSzu-Hsien WuTakanobu MashikoKentaro DoiShinichiro KunoKahori KinoshitaKoji KanayamaRintaro AsahiAtaru SunagaKotaro YoshimuraNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017) |
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Medicine R Science Q |
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Medicine R Science Q Jingwei Feng Kazuhide Mineda Szu-Hsien Wu Takanobu Mashiko Kentaro Doi Shinichiro Kuno Kahori Kinoshita Koji Kanayama Rintaro Asahi Ataru Sunaga Kotaro Yoshimura An injectable non-cross-linked hyaluronic-acid gel containing therapeutic spheroids of human adipose-derived stem cells |
| description |
Abstract For chronic wounds, the delivery of stem cells in spheroidal structures can enhance graft survival and stem cell potency. We describe an easy method for the 3D culture of adipose-derived stem/stromal cells (ASCs) to prepare a ready-to-use injectable. We transferred suspensions of monolayer-cultured ASCs to a syringe containing hyaluronic acid (HA) gel, and then incubated the syringe as a 3D culture vessel. Spheroids of cells formed after 12 h. We found that 6 × 106 ASCs/ml in 3% HA gel achieved the highest spheroid density with appropriate spheroid sizes (20–100 µm). Immunocytology revealed that the stem cell markers, NANOG, OCT3/4, SOX-2, and SSEA-3 were up-regulated in the ASC spheroids compared with those in nonadherent-dish spheroids or in monolayer cultured ASCs. In delayed wound healing mice models, diabetic ulcers treated with ASC spheroids demonstrated faster wound epithelialization with thicker dermis than those treated with vehicle alone or monolayer cultured ASCs. In irradiated skin ulcers in immunodeficient mice, ASC spheroids exhibited faster healing and outstanding angiogenic potential partly by direct differentiation into α-SMA+ pericytes. Our method of 3D in-syringe HA gel culture produced clinically relevant amounts of ready-to-inject human ASC microspheroids that exhibited superior stemness in vitro and therapeutic efficacy in pathological wound repair in vivo. |
| format |
article |
| author |
Jingwei Feng Kazuhide Mineda Szu-Hsien Wu Takanobu Mashiko Kentaro Doi Shinichiro Kuno Kahori Kinoshita Koji Kanayama Rintaro Asahi Ataru Sunaga Kotaro Yoshimura |
| author_facet |
Jingwei Feng Kazuhide Mineda Szu-Hsien Wu Takanobu Mashiko Kentaro Doi Shinichiro Kuno Kahori Kinoshita Koji Kanayama Rintaro Asahi Ataru Sunaga Kotaro Yoshimura |
| author_sort |
Jingwei Feng |
| title |
An injectable non-cross-linked hyaluronic-acid gel containing therapeutic spheroids of human adipose-derived stem cells |
| title_short |
An injectable non-cross-linked hyaluronic-acid gel containing therapeutic spheroids of human adipose-derived stem cells |
| title_full |
An injectable non-cross-linked hyaluronic-acid gel containing therapeutic spheroids of human adipose-derived stem cells |
| title_fullStr |
An injectable non-cross-linked hyaluronic-acid gel containing therapeutic spheroids of human adipose-derived stem cells |
| title_full_unstemmed |
An injectable non-cross-linked hyaluronic-acid gel containing therapeutic spheroids of human adipose-derived stem cells |
| title_sort |
injectable non-cross-linked hyaluronic-acid gel containing therapeutic spheroids of human adipose-derived stem cells |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/9511dc0efc514fe0a0baef4c277d14dd |
| work_keys_str_mv |
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| _version_ |
1718394997029470208 |