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The influence of hydrogel modulus on the proliferation and differentiation of encapsulated neural stem cells
Authors:Akhilesh Banerjee  Manish Arha  Soumitra Choudhary  Randolph S. Ashton  Surita R. Bhatia  David V. Schaffer  Ravi S. Kane
Affiliation:1. The Howard P. Isermann Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, NY 12180, USA;2. Department of Chemical Engineering, University of Massachusetts-Amherst, Amherst, MA 01003, USA;3. Department of Chemical Engineering, Department of Bioengineering, and the Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, CA 94720, USA;1. Department of General Thoracic Surgery, Juntendo University School of Medicine, Japan;2. Department of Respiratory Medicine, Juntendo University School of Medicine, Japan;3. Department of Orthopedic Surgery, Juntendo University School of Medicine, Japan;4. Department of Pathology, Institute of Medical Science (Medical Research Center), Tokyo Medical University, Japan;5. Department of Medical Genomics, Graduate School of Medicine, The University of Tokyo, Japan;6. Department of Human Pathology, Juntendo University School of Medicine, Japan;7. Department of Experimental Therapeutics, National Cancer Center Hospital, Japan;8. Departments of Cellular Signaling, Graduate School of Medicine, The University of Tokyo, Japan;9. Pathology Project for Molecular Targets, The Cancer Institute, Japanese Foundation for Cancer Research, Japan;10. National Cancer Center Research Institute, Tokyo, Japan;1. Department of Neurology of Weifang People’s Hospital, Weifang 261041, Shandong, PR China;2. Department of Medical Laboratory of Beijing Children’s Hospital, Capital Medical University, Beijing 100053, PR China;3. Clinical Laboratory of Xuanwu Hospital, Capital Medical University, Beijing 100053, PR China;1. Department of Chemical and Biomolecular Engineering, The University of Akron, Akron, OH, USA;2. Akron General Medical Center, Akron, OH, USA;1. Wake Forest Institute for Regenerative Medicine, Richard H. Dean Biomedical Research Building, 391 Technology Way, Winston-Salem, NC 27101, United States;2. Wake Forest University, Department of Physics, 7507 Reynolda Station, Winston-Salem, NC 27109, United States;1. Russell H. Morgan Dept. of Radiology and Radiological Science, Division of MR Research, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA;2. Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA;3. Dept. of Chemical & Biomolecular Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA;4. Dept. of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA;5. Dept of Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA;6. Department of Radiology, Faculty of Medical Sciences, University of Warmia and Mazury, Olsztyn, Poland;1. Battelle Memorial Institute, 505 King Ave., Columbus, OH, 43201, USA;2. Ohio Bureau of Criminal Investigation, London, OH, 43140, USA
Abstract:There has been an increasing interest in understanding how the mechanical properties of the microenvironment influence stem cell fate. We describe studies of the proliferation and differentiation of neural stem cells (NSCs) encapsulated within three-dimensional scaffolds – alginate hydrogels – whose elastic moduli were varied over two orders of magnitude. The rate of proliferation of neural stem cells decreased with increase in the modulus of the hydrogels. Moreover, we observed the greatest enhancement in expression of the neuronal marker β-tubulin III within the softest hydrogels, which had an elastic modulus comparable to that of brain tissues. To our knowledge, this work represents the first demonstration of the influence of modulus on NSC differentiation in three-dimensional scaffolds. Three-dimensional scaffolds that control stem cell fate would be broadly useful for applications in regenerative medicine and tissue engineering.
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