Surface Tethered Epidermal Growth Factor Protects Proliferating and Differentiating Multipotential Stromal Cells from FasL-Induced Apoptosis
Multipotential stromal cells or mesenchymal stem cells (MSCs) have been proposed as aids in regenerating bone and adipose tissues, as these cells form osteoblasts and adipocytes. A major obstacle to this use of MSC is the initial loss of cells postimplantation. This cell death in part is due to ubiq...
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| Format: | Article |
| Language: | en_US |
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Wiley Blackwell
2015
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| Online Access: | http://hdl.handle.net/1721.1/99377 https://orcid.org/0000-0002-1801-5548 |
| _version_ | 1811096551744864256 |
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| author | Rodrigues, Melanie Blair, Harry Stockdale, Linda Wells, Alan Griffith, Linda G. |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Rodrigues, Melanie Blair, Harry Stockdale, Linda Wells, Alan Griffith, Linda G. |
| author_sort | Rodrigues, Melanie |
| collection | MIT |
| description | Multipotential stromal cells or mesenchymal stem cells (MSCs) have been proposed as aids in regenerating bone and adipose tissues, as these cells form osteoblasts and adipocytes. A major obstacle to this use of MSC is the initial loss of cells postimplantation. This cell death in part is due to ubiquitous nonspecific inflammatory cytokines such as FasL generated in the implant site. Our group previously found that soluble epidermal growth factor (sEGF) promotes MSC expansion. Furthermore, tethering EGF (tEGF) onto a two-dimensional surface altered MSC responses, by restricting epidermal growth factor receptor (EGFR) to the cell surface, causing sustained activation of EGFR, and promoting survival from FasL-induced death. sEGF by causing internalization of EGFR does not support MSC survival. However, for tEGF to be useful in bone regeneration, it needs to allow for MSC differentiation into osteoblasts while also protecting emerging osteoblasts from apoptosis. tEGF did not block induced differentiation of MSCs into osteoblasts, or adipocytes, a common default MSC-differentiation pathway. MSC-derived preosteoblasts showed increased Fas levels and became more susceptible to FasL-induced death, which tEGF prevented. Differentiating adipocytes underwent a reduction in Fas expression and became resistant to FasL-induced death, with tEGF having no further survival effect. tEGF protected undifferentiated MSC from combined insults of FasL, serum deprivation, and physiologic hypoxia. Additionally, tEGF was dominant in the face of sEGF to protect MSC from FasL-induced death. Our results suggest that MSCs and differentiating osteoblasts need protective signals to survive in the inflammatory wound milieu and that tEGF can serve this function. |
| first_indexed | 2024-09-23T16:45:29Z |
| format | Article |
| id | mit-1721.1/99377 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T16:45:29Z |
| publishDate | 2015 |
| publisher | Wiley Blackwell |
| record_format | dspace |
| spelling | mit-1721.1/993772022-09-29T21:16:21Z Surface Tethered Epidermal Growth Factor Protects Proliferating and Differentiating Multipotential Stromal Cells from FasL-Induced Apoptosis Rodrigues, Melanie Blair, Harry Stockdale, Linda Wells, Alan Griffith, Linda G. Massachusetts Institute of Technology. Department of Biological Engineering Stockdale, Linda Griffith, Linda G. Multipotential stromal cells or mesenchymal stem cells (MSCs) have been proposed as aids in regenerating bone and adipose tissues, as these cells form osteoblasts and adipocytes. A major obstacle to this use of MSC is the initial loss of cells postimplantation. This cell death in part is due to ubiquitous nonspecific inflammatory cytokines such as FasL generated in the implant site. Our group previously found that soluble epidermal growth factor (sEGF) promotes MSC expansion. Furthermore, tethering EGF (tEGF) onto a two-dimensional surface altered MSC responses, by restricting epidermal growth factor receptor (EGFR) to the cell surface, causing sustained activation of EGFR, and promoting survival from FasL-induced death. sEGF by causing internalization of EGFR does not support MSC survival. However, for tEGF to be useful in bone regeneration, it needs to allow for MSC differentiation into osteoblasts while also protecting emerging osteoblasts from apoptosis. tEGF did not block induced differentiation of MSCs into osteoblasts, or adipocytes, a common default MSC-differentiation pathway. MSC-derived preosteoblasts showed increased Fas levels and became more susceptible to FasL-induced death, which tEGF prevented. Differentiating adipocytes underwent a reduction in Fas expression and became resistant to FasL-induced death, with tEGF having no further survival effect. tEGF protected undifferentiated MSC from combined insults of FasL, serum deprivation, and physiologic hypoxia. Additionally, tEGF was dominant in the face of sEGF to protect MSC from FasL-induced death. Our results suggest that MSCs and differentiating osteoblasts need protective signals to survive in the inflammatory wound milieu and that tEGF can serve this function. National Institute of General Medical Sciences (U.S.) (GM069668) National Institute of Dental and Craniofacial Research (U.S.) (DE019523) 2015-10-20T19:56:57Z 2015-10-20T19:56:57Z 2012-12 2012-05 Article http://purl.org/eprint/type/JournalArticle 10665099 1549-4918 http://hdl.handle.net/1721.1/99377 Rodrigues, Melanie, Harry Blair, Linda Stockdale, Linda Griffith, and Alan Wells. “Surface Tethered Epidermal Growth Factor Protects Proliferating and Differentiating Multipotential Stromal Cells from FasL-Induced Apoptosis.” STEM CELLS 31, no. 1 (December 19, 2012): 104–116. https://orcid.org/0000-0002-1801-5548 en_US http://dx.doi.org/10.1002/stem.1215 Stem Cells Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Wiley Blackwell PMC |
| spellingShingle | Rodrigues, Melanie Blair, Harry Stockdale, Linda Wells, Alan Griffith, Linda G. Surface Tethered Epidermal Growth Factor Protects Proliferating and Differentiating Multipotential Stromal Cells from FasL-Induced Apoptosis |
| title | Surface Tethered Epidermal Growth Factor Protects Proliferating and Differentiating Multipotential Stromal Cells from FasL-Induced Apoptosis |
| title_full | Surface Tethered Epidermal Growth Factor Protects Proliferating and Differentiating Multipotential Stromal Cells from FasL-Induced Apoptosis |
| title_fullStr | Surface Tethered Epidermal Growth Factor Protects Proliferating and Differentiating Multipotential Stromal Cells from FasL-Induced Apoptosis |
| title_full_unstemmed | Surface Tethered Epidermal Growth Factor Protects Proliferating and Differentiating Multipotential Stromal Cells from FasL-Induced Apoptosis |
| title_short | Surface Tethered Epidermal Growth Factor Protects Proliferating and Differentiating Multipotential Stromal Cells from FasL-Induced Apoptosis |
| title_sort | surface tethered epidermal growth factor protects proliferating and differentiating multipotential stromal cells from fasl induced apoptosis |
| url | http://hdl.handle.net/1721.1/99377 https://orcid.org/0000-0002-1801-5548 |
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