Journal
BIOMATERIALS
Volume 173, Issue -, Pages 34-46Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2018.04.048
Keywords
Muscle stem cells; Transplantation; Skeletal muscle; Hyaluronan; Methylcellulose; Bioactive; Injectable hydrogel
Funding
- Natural Sciences and Engineering Research Council of Canada [RGPIN 435724-13, 950-231201]
- Ontario Provincial Government [ER15-11-073]
- Canada Foundation for Innovation [31390]
- Toronto Western Arthritis Program
- University of Toronto Faculty of Medicine Dean's Fund
- Canadian Institutes of Health Research [ONM-137370]
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Adult skeletal muscle tissue harbors the capacity for self-repair due to the presence of tissue resident muscle stem cells (MuSCs). Advances in the area of prospective MuSC isolation demonstrated the potential of cell transplantation therapy as a regenerative medicine strategy to restore strength and long-term regenerative capacity to aged, injured, or diseased skeletal muscle tissue. However, cell loss during ejection, limits to post-injection proliferation, and poor donor cell dispersion distal to the injection site are amongst hurdles to overcome to maximize MuSC transplant impact. Here, we assess a physical blend of hyaluronan and methylcellulose (HAMC) as a bioactive, shear thinning hydrogel cell delivery system to improve MuSC transplantation efficiency. Using in vivo transplantation studies, we found that the HAMC delivery system results in a >45% increase in the number of donor-derived fibers as compared to saline delivery. We demonstrate that increases in donor-derived fibers when using HAMC are attributed to increased MuSC proliferation via a CD44-independent mechanism, preventing injected cell active clearance, and supporting in vivo expansion by delaying differentiation. Furthermore, we observed a significant improvement in donor fiber dispersion when MuSCs were delivered in HAMC. Our study results suggest that HAMC is a promising muscle stem cell delivery vehicle. (C) 2018 Elsevier Ltd. All rights reserved.
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