Biophysical and chemical effects of fibrin on mesenchymal stromal cell gene expression |
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| Authors: | Ngan F Huang Julia Chu Randall J Lee Song Li |
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| Institution: | 1. University of California Berkeley and University of California San Francisco Joint Graduate Program in Bioengineering, MC 1762, Berkeley, CA 94720-1762, USA;2. Department of Bioengineering, University of California Berkeley, MC 1762, Berkeley, CA 94720-1762, USA;3. Cardiac Electrophysiology, MU East Tower, Box 1354, University of California San Francisco, 500 Parnassus Avenue, San Francisco, CA 94143-1354, USA;1. Molecular Cellular and Integrative Physiology Graduate Group, University of California, Davis, CA, United States;2. Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, CA, United States;3. Department of Biomedical Engineering, University of California, Davis, CA, United States;4. Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California, Davis, Davis, CA, United States;1. Quinze-Vingts National Ophthalmology Hospital, UPMC-Sorbonne Universities, Paris, France;2. INSERM UMR S 968, Institut de la Vision, Paris, France;3. Sorbonne Universités, UPMC Univ Paris 06, UMR S 968, Institut de la Vision, Paris, France;4. CNRS, UMR 7210, Paris, France;1. Department of Neurosurgery, Taipei Medical University Hospital, Taipei, Taiwan, ROC;2. School of Medicine, Taipei Medical University, Taipei, Taiwan, ROC;3. Stem Cell Research Center, Taipei Medical University, Taipei, Taiwan, ROC;4. Graduate Institute of Biomedical Materials and Engineering, Taipei Medical University, Taipei, Taiwan, ROC;5. Food Industry Research and Development Institute Culture Collection and Research Center, Taiwan, ROC;6. Department of Orthopedic Surgery, The Affiliated Hospital, Guangdong Medical College, Zhanjiang 524001, China;7. College of Oral Medicine, Taipei Medical University, Taipei, Taiwan, ROC;8. Department of Urology, Taipei Medical University Hospital, Taipei, Taiwan, ROC;9. Institute of Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA;10. Cancer Center, Taipei Medical University and Hospital, Taipei, Taiwan, ROC;2. Comprehensive Ophthalmology and Cataract Consultation Service, Massachusetts Eye & Ear Infirmary, Boston, Massachusetts;3. Retina Service, Massachusetts Eye & Ear Infirmary, Boston, Massachusetts;4. Glaucoma Service, Massachusetts Eye & Ear Infirmary, Boston, Massachusetts |
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| Abstract: | Mesenchymal stromal cells (MSCs) are multipotent cells that have high expansion yields and fibrin is a native extracellular matrix (ECM) material widely used for cell delivery and surgery. MSCs and fibrin have tremendous potential for tissue engineering applications, but the effect of fibrin on MSCs is not well characterized. The purpose of this study was to analyze the role of fibrin in modulating MSC phenotype by gene expression analysis. The results demonstrate that fibrin up-regulated MSC gene expression of vasculogenic (FLK1, ACTA2, VECAD, SM22 and CNN1), myogenic (MYF5 and MYH13), neurogenic (TH and GFAP) and chondrogenic (COL2A1) markers after 5 days incubation. These gene expression results were supported by induction of expression on the protein level for early lineage-specific markers such as ACTA2, FLK1 and MYF5. The ability of fibrin to modulate MSC gene expression was not affected by matrix pore size (80–110 μm diameter) or Young’s modulus (5–25 kPa) and the differential expression of some phenotypic markers could be partially mimicked by other ECM proteins, such as fibronectin and collagen I. In some cases the inductive effect of fibrin on gene expression could be further augmented by the treatment with growth factors such as nerve growth factor. However, the effect of fibrin appeared to be limited, as MSCs did not differentiate into fully mature cells based on immunofluorescence staining after 12 days. This body of work provides a rational approach for studying the interactions of MSC with fibrin, which has important therapeutic implications for the delivery of stem cells. |
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