Scaffold-Free Fabrication of Osteoinductive Cellular Constructs Using Mouse Gingiva-Derived Induced Pluripotent Stem Cells
Three-dimensional (3D) cell constructs are expected to provide osteoinductive materials to develop cell-based therapies for bone regeneration. The proliferation and spontaneous aggregation capability of induced pluripotent stem cells (iPSCs) thus prompted us to fabricate a scaffold-free iPSC constru...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Hindawi Limited
2016-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2016/6240794 |
| _version_ | 1798045150516084736 |
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| author | Hiroko Okawa Hiroki Kayashima Jun-Ichi Sasaki Jiro Miura Yuya Kamano Yukihiro Kosaka Satoshi Imazato Hirofumi Yatani Takuya Matsumoto Hiroshi Egusa |
| author_facet | Hiroko Okawa Hiroki Kayashima Jun-Ichi Sasaki Jiro Miura Yuya Kamano Yukihiro Kosaka Satoshi Imazato Hirofumi Yatani Takuya Matsumoto Hiroshi Egusa |
| author_sort | Hiroko Okawa |
| collection | DOAJ |
| description | Three-dimensional (3D) cell constructs are expected to provide osteoinductive materials to develop cell-based therapies for bone regeneration. The proliferation and spontaneous aggregation capability of induced pluripotent stem cells (iPSCs) thus prompted us to fabricate a scaffold-free iPSC construct as a transplantation vehicle. Embryoid bodies of mouse gingival fibroblast-derived iPSCs (GF-iPSCs) were seeded in a cell chamber with a round-bottom well made of a thermoresponsive hydrogel. Collected ball-like cell constructs were cultured in osteogenic induction medium for 30 days with gentle shaking, resulting in significant upregulation of osteogenic marker genes. The constructs consisted of an inner region of unstructured cell mass and an outer osseous tissue region that was surrounded by osteoblast progenitor-like cells. The outer osseous tissue was robustly calcified with elemental calcium and phosphorous as well as hydroxyapatite. Subcutaneous transplantation of the GF-iPSC constructs into immunodeficient mice contributed to extensive ectopic bone formation surrounded by teratoma tissue. These results suggest that mouse GF-iPSCs could facilitate the fabrication of osteoinductive scaffold-free 3D cell constructs, in which the calcified regions and surrounding osteoblasts may function as scaffolds and drivers of osteoinduction, respectively. With incorporation of technologies to inhibit teratoma formation, this system could provide a promising strategy for bone regenerative therapies. |
| first_indexed | 2024-04-11T23:16:02Z |
| format | Article |
| id | doaj.art-e8d4bda8eae8451e8c38a1f1a4f164dc |
| institution | Directory Open Access Journal |
| issn | 1687-966X 1687-9678 |
| language | English |
| last_indexed | 2024-04-11T23:16:02Z |
| publishDate | 2016-01-01 |
| publisher | Hindawi Limited |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj.art-e8d4bda8eae8451e8c38a1f1a4f164dc2022-12-22T03:57:37ZengHindawi LimitedStem Cells International1687-966X1687-96782016-01-01201610.1155/2016/62407946240794Scaffold-Free Fabrication of Osteoinductive Cellular Constructs Using Mouse Gingiva-Derived Induced Pluripotent Stem CellsHiroko Okawa0Hiroki Kayashima1Jun-Ichi Sasaki2Jiro Miura3Yuya Kamano4Yukihiro Kosaka5Satoshi Imazato6Hirofumi Yatani7Takuya Matsumoto8Hiroshi Egusa9Division of Molecular and Regenerative Prosthodontics, Tohoku University Graduate School of Dentistry, Sendai, Miyagi 980-8575, JapanDepartment of Fixed Prosthodontics, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka, Suita, Osaka 565-0871, JapanDepartment of Biomaterials Science, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka, Suita, Osaka 565-0871, JapanDivision for Interdisciplinary Dentistry, Osaka University Dental Hospital, 1-8 Yamadaoka, Suita, Osaka 565-0871, JapanDivision of Molecular and Regenerative Prosthodontics, Tohoku University Graduate School of Dentistry, Sendai, Miyagi 980-8575, JapanDivision of Molecular and Regenerative Prosthodontics, Tohoku University Graduate School of Dentistry, Sendai, Miyagi 980-8575, JapanDepartment of Biomaterials Science, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka, Suita, Osaka 565-0871, JapanDepartment of Fixed Prosthodontics, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka, Suita, Osaka 565-0871, JapanDepartment of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikada-cho, Kita-ku, Okayama 700-8525, JapanDivision of Molecular and Regenerative Prosthodontics, Tohoku University Graduate School of Dentistry, Sendai, Miyagi 980-8575, JapanThree-dimensional (3D) cell constructs are expected to provide osteoinductive materials to develop cell-based therapies for bone regeneration. The proliferation and spontaneous aggregation capability of induced pluripotent stem cells (iPSCs) thus prompted us to fabricate a scaffold-free iPSC construct as a transplantation vehicle. Embryoid bodies of mouse gingival fibroblast-derived iPSCs (GF-iPSCs) were seeded in a cell chamber with a round-bottom well made of a thermoresponsive hydrogel. Collected ball-like cell constructs were cultured in osteogenic induction medium for 30 days with gentle shaking, resulting in significant upregulation of osteogenic marker genes. The constructs consisted of an inner region of unstructured cell mass and an outer osseous tissue region that was surrounded by osteoblast progenitor-like cells. The outer osseous tissue was robustly calcified with elemental calcium and phosphorous as well as hydroxyapatite. Subcutaneous transplantation of the GF-iPSC constructs into immunodeficient mice contributed to extensive ectopic bone formation surrounded by teratoma tissue. These results suggest that mouse GF-iPSCs could facilitate the fabrication of osteoinductive scaffold-free 3D cell constructs, in which the calcified regions and surrounding osteoblasts may function as scaffolds and drivers of osteoinduction, respectively. With incorporation of technologies to inhibit teratoma formation, this system could provide a promising strategy for bone regenerative therapies.http://dx.doi.org/10.1155/2016/6240794 |
| spellingShingle | Hiroko Okawa Hiroki Kayashima Jun-Ichi Sasaki Jiro Miura Yuya Kamano Yukihiro Kosaka Satoshi Imazato Hirofumi Yatani Takuya Matsumoto Hiroshi Egusa Scaffold-Free Fabrication of Osteoinductive Cellular Constructs Using Mouse Gingiva-Derived Induced Pluripotent Stem Cells Stem Cells International |
| title | Scaffold-Free Fabrication of Osteoinductive Cellular Constructs Using Mouse Gingiva-Derived Induced Pluripotent Stem Cells |
| title_full | Scaffold-Free Fabrication of Osteoinductive Cellular Constructs Using Mouse Gingiva-Derived Induced Pluripotent Stem Cells |
| title_fullStr | Scaffold-Free Fabrication of Osteoinductive Cellular Constructs Using Mouse Gingiva-Derived Induced Pluripotent Stem Cells |
| title_full_unstemmed | Scaffold-Free Fabrication of Osteoinductive Cellular Constructs Using Mouse Gingiva-Derived Induced Pluripotent Stem Cells |
| title_short | Scaffold-Free Fabrication of Osteoinductive Cellular Constructs Using Mouse Gingiva-Derived Induced Pluripotent Stem Cells |
| title_sort | scaffold free fabrication of osteoinductive cellular constructs using mouse gingiva derived induced pluripotent stem cells |
| url | http://dx.doi.org/10.1155/2016/6240794 |
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