Contrasting Effects of Vasculogenic Induction Upon Biaxial Bioreactor Stimulation of Mesenchymal Stem Cells and Endothelial Progenitor Cells Cocultures in Three-Dimensional Scaffolds under in Vitro and in Vivo Paradigms for Vascularized Bone Tissue Engineering
Clinical translation of bone tissue engineering approaches for fracture repair has been hampered by inadequate vascularization required for maintaining cell survival, skeletal regeneration, and remodeling. The potential of vasculature formation within tissue-engineered grafts depends on various fact...
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Mary Ann Liebert, Inc.
2013
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| Online Access: | http://hdl.handle.net/1721.1/78840 https://orcid.org/0000-0002-7232-304X |
| _version_ | 1826199418033930240 |
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| author | Liu, Yuchun Teoh, Swee-Hin Chong, Mark S. K. Yeow, Chen-Hua Kamm, Roger Dale Choolani, Mahesh Chan, Jerry K. Y. |
| author2 | Massachusetts Institute of Technology. Department of Mechanical Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Mechanical Engineering Liu, Yuchun Teoh, Swee-Hin Chong, Mark S. K. Yeow, Chen-Hua Kamm, Roger Dale Choolani, Mahesh Chan, Jerry K. Y. |
| author_sort | Liu, Yuchun |
| collection | MIT |
| description | Clinical translation of bone tissue engineering approaches for fracture repair has been hampered by inadequate vascularization required for maintaining cell survival, skeletal regeneration, and remodeling. The potential of vasculature formation within tissue-engineered grafts depends on various factors, including an appropriate choice of scaffold and its microarchitectural design for the support of tissue ingrowth and vessel infiltration, vasculogenic potential of cell types and mechanostimulation on cells to enhance cytokine expression. Here, we demonstrated the effect of biomechanical stimulation on vasculogenic and bone-forming capacity of umbilical-cord-blood endothelial progenitor cells (UCB-EPC) and human fetal bone marrow-derived mesenchymal stem cell (hfMSC) seeded within macroporous scaffolds and cocultured dynamically in a biaxial bioreactor. Dynamically cultured EPC/hfMSC constructs generated greater mineralization and calcium deposition consistently over 14 days of culture (1.7-fold on day 14; p<0.05). However, in vitro vessel formation was not observed as compared to an extensive EPC-vessel network formed under static culture on day 7. Subsequent subcutaneous implantations in NOD/SCID mice showed 1.4-fold higher human:mouse cell chimerism (p<0.001), with a more even cellular distribution throughout the dynamically cultured scaffolds. In addition, there was earlier evidence of vessel infiltration into the scaffold and a trend toward increased ectopic bone formation, suggesting improved efficacy and cellular survival through early vascularization upon biomechanical stimulation. The integrative use of bioreactor culture systems with macroporous scaffolds and cocultured osteogenic and vasculogenic cells promotes maturation of EPC/hfMSC-scaffold grafts necessary for vascularized bone tissue engineering applications. |
| first_indexed | 2024-09-23T11:19:36Z |
| format | Article |
| id | mit-1721.1/78840 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T11:19:36Z |
| publishDate | 2013 |
| publisher | Mary Ann Liebert, Inc. |
| record_format | dspace |
| spelling | mit-1721.1/788402022-10-01T02:49:16Z Contrasting Effects of Vasculogenic Induction Upon Biaxial Bioreactor Stimulation of Mesenchymal Stem Cells and Endothelial Progenitor Cells Cocultures in Three-Dimensional Scaffolds under in Vitro and in Vivo Paradigms for Vascularized Bone Tissue Engineering Liu, Yuchun Teoh, Swee-Hin Chong, Mark S. K. Yeow, Chen-Hua Kamm, Roger Dale Choolani, Mahesh Chan, Jerry K. Y. Massachusetts Institute of Technology. Department of Mechanical Engineering Singapore-MIT Alliance in Research and Technology (SMART) Kamm, Roger Dale Clinical translation of bone tissue engineering approaches for fracture repair has been hampered by inadequate vascularization required for maintaining cell survival, skeletal regeneration, and remodeling. The potential of vasculature formation within tissue-engineered grafts depends on various factors, including an appropriate choice of scaffold and its microarchitectural design for the support of tissue ingrowth and vessel infiltration, vasculogenic potential of cell types and mechanostimulation on cells to enhance cytokine expression. Here, we demonstrated the effect of biomechanical stimulation on vasculogenic and bone-forming capacity of umbilical-cord-blood endothelial progenitor cells (UCB-EPC) and human fetal bone marrow-derived mesenchymal stem cell (hfMSC) seeded within macroporous scaffolds and cocultured dynamically in a biaxial bioreactor. Dynamically cultured EPC/hfMSC constructs generated greater mineralization and calcium deposition consistently over 14 days of culture (1.7-fold on day 14; p<0.05). However, in vitro vessel formation was not observed as compared to an extensive EPC-vessel network formed under static culture on day 7. Subsequent subcutaneous implantations in NOD/SCID mice showed 1.4-fold higher human:mouse cell chimerism (p<0.001), with a more even cellular distribution throughout the dynamically cultured scaffolds. In addition, there was earlier evidence of vessel infiltration into the scaffold and a trend toward increased ectopic bone formation, suggesting improved efficacy and cellular survival through early vascularization upon biomechanical stimulation. The integrative use of bioreactor culture systems with macroporous scaffolds and cocultured osteogenic and vasculogenic cells promotes maturation of EPC/hfMSC-scaffold grafts necessary for vascularized bone tissue engineering applications. Singapore. National Medical Research Council (NMRC/1179/2008) Singapore. National Medical Research Council (NMRC/1268/2010) 2013-05-07T18:25:33Z 2013-05-07T18:25:33Z 2012-12 2012-03 Article http://purl.org/eprint/type/JournalArticle 1937-3341 1937-335X http://hdl.handle.net/1721.1/78840 Liu, Yuchun et al. “Contrasting Effects of Vasculogenic Induction Upon Biaxial Bioreactor Stimulation of Mesenchymal Stem Cells and Endothelial Progenitor Cells Cocultures in Three-Dimensional Scaffolds Under In Vitro and In Vivo Paradigms for Vascularized Bone Tissue Engineering.” Tissue Engineering Part A 19.7-8 (2013): 893–904. ©2012 Mary Ann Liebert, Inc. https://orcid.org/0000-0002-7232-304X en_US http://dx.doi.org/10.1089/ten.tea.2012.0187 Tissue Engineering. Part A Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Mary Ann Liebert, Inc. Mary Ann Leibert |
| spellingShingle | Liu, Yuchun Teoh, Swee-Hin Chong, Mark S. K. Yeow, Chen-Hua Kamm, Roger Dale Choolani, Mahesh Chan, Jerry K. Y. Contrasting Effects of Vasculogenic Induction Upon Biaxial Bioreactor Stimulation of Mesenchymal Stem Cells and Endothelial Progenitor Cells Cocultures in Three-Dimensional Scaffolds under in Vitro and in Vivo Paradigms for Vascularized Bone Tissue Engineering |
| title | Contrasting Effects of Vasculogenic Induction Upon Biaxial Bioreactor Stimulation of Mesenchymal Stem Cells and Endothelial Progenitor Cells Cocultures in Three-Dimensional Scaffolds under in Vitro and in Vivo Paradigms for Vascularized Bone Tissue Engineering |
| title_full | Contrasting Effects of Vasculogenic Induction Upon Biaxial Bioreactor Stimulation of Mesenchymal Stem Cells and Endothelial Progenitor Cells Cocultures in Three-Dimensional Scaffolds under in Vitro and in Vivo Paradigms for Vascularized Bone Tissue Engineering |
| title_fullStr | Contrasting Effects of Vasculogenic Induction Upon Biaxial Bioreactor Stimulation of Mesenchymal Stem Cells and Endothelial Progenitor Cells Cocultures in Three-Dimensional Scaffolds under in Vitro and in Vivo Paradigms for Vascularized Bone Tissue Engineering |
| title_full_unstemmed | Contrasting Effects of Vasculogenic Induction Upon Biaxial Bioreactor Stimulation of Mesenchymal Stem Cells and Endothelial Progenitor Cells Cocultures in Three-Dimensional Scaffolds under in Vitro and in Vivo Paradigms for Vascularized Bone Tissue Engineering |
| title_short | Contrasting Effects of Vasculogenic Induction Upon Biaxial Bioreactor Stimulation of Mesenchymal Stem Cells and Endothelial Progenitor Cells Cocultures in Three-Dimensional Scaffolds under in Vitro and in Vivo Paradigms for Vascularized Bone Tissue Engineering |
| title_sort | contrasting effects of vasculogenic induction upon biaxial bioreactor stimulation of mesenchymal stem cells and endothelial progenitor cells cocultures in three dimensional scaffolds under in vitro and in vivo paradigms for vascularized bone tissue engineering |
| url | http://hdl.handle.net/1721.1/78840 https://orcid.org/0000-0002-7232-304X |
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