Improved Transplanted Stem Cell Survival in a Polymer Gel Supplemented With Tenascin C Accelerates Healing and Reduces Scarring of Murine Skin Wounds
| Autor: | Alan Wells, Melanie Rodrigues, Austin Nuschke, Cecelia C. Yates, Jason Dechant, Diana Whaley, Donald P. Taylor |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Angiogenesis Cell Survival Polymers Biomedical Engineering lcsh:Medicine Tenascin Mesenchymal Stem Cell Transplantation Skin Diseases Article Polyethylene Glycols Extracellular matrix Cell therapy 03 medical and health sciences Mice medicine Animals Cells Cultured Skin Transplantation Wound Healing biology integumentary system business.industry lcsh:R Tenascin C Mesenchymal stem cell Mesenchymal Stem Cells Cell Biology Flow Cytometry Surgery Extracellular Matrix Mice Inbred C57BL 030104 developmental biology biology.protein Cancer research Female Collagen Stem cell Wound healing business |
| Zdroj: | Cell Transplantation, Vol 26 (2017) |
| ISSN: | 1555-3892 |
| Popis: | Mesenchymal stem cells (MSCs) remain of great interest in regenerative medicine because of their ability to home to sites of injury, differentiate into a variety of relevant lineages, and modulate inflammation and angiogenesis through paracrine activity. Many studies have found that despite the promise of MSC therapy, cell survival upon implant is highly limited and greatly reduces the therapeutic utility of MSCs. The matrikine tenascin C, a protein expressed often at the edges of a healing wound, contains unique EGF-like repeats that are able to bind EGFR at low affinities and induce downstream prosurvival signaling without inducing receptor internalization. In this study, we utilized tenascin C in a collagen/GAG-based polymer (TPolymer) that has been shown to be beneficial for skin wound healing, incorporating human MSCs into the polymer prior to application to mouse punch biopsy wound beds. We found that the TPolymer was able to promote MSC survival for 21 days in vivo, leading to associated improvements in wound healing such as dermal maturation and collagen content. This was most marked in a model of hypertrophic scarring, in which the scar formation was limited. This approach also reduced the inflammatory response in the wound bed, limiting CD3e+ cell invasion by approximately 50% in the early wound-healing process, while increasing the numbers of endothelial cells during the first week of wound healing as well. Ultimately, this matrikine-based approach to improving MSC survival may be of great use across a variety of cell therapies utilizing matrices as delivery vehicles for cells. |
| Databáze: | OpenAIRE |
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