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Implantable Biomimetic Niche for Satellite Cell Transplantation
Author(s) -
Jang Young Charles,
Han Woojin,
Shin Eunjung,
Garcia Andres
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.1082.1
Subject(s) - microbiology and biotechnology , transplantation , stem cell , laminin , regeneration (biology) , tissue engineering , chemistry , biology , immunology , extracellular matrix , biomedical engineering , medicine
To maintain skeletal muscle homeostasis and to repair damaged muscle, a functional pool of muscle stem cell, also known as satellite cells (SC), undergoes asymmetric division in which committed progenies proliferate, differentiate, and fuse with existing myofibers or form de novo myofibers, while other populations of SC progeny self‐renew to replenish the quiescent stem cell pool for future rounds of regeneration. Due to these unique properties and recent advances in isolation technique, SC has been an attractive target for interventions, and cell‐based therapy has been extensively studied to treat a variety of muscle wasting conditions. While direct transplantation of SC contributes to muscle regeneration to some degree, the clinical efficacy of direct cell transplantation is severely limited by sub‐optimal engraftment, survival, and lack of functional benefits. To overcome these challenges, we engineered a synthetic matrix that recapitulates the key components of the SC microenvironment using hydrogels based on maleimide‐end functionalized poly(ethylene) glycol macromers. A 3D culture of FACS purified SCs (Sca‐1 − , CD45 − , Mac‐1 − , Ter‐119 − , CXCR4 + , and β1‐integrin + ) in these platforms revealed that type of cell‐adhesive ligand, mechanical property, and mesh size of the matrix have a profound impact on the survival, proliferation, and differentiation of the SCs in vitro . Specifically, presentation of RGD peptide ligand resulted in significantly higher survival, colony size, density, and differentiation compared to scrambled RDG peptide (control) and synthetic laminin peptides (YIGSR and C16). The storage modulus and mesh size of the synthetic hydrogel was further optimized by varying the weight percentage of the poly(ethylene) glycol macromer density, where 3–4% (w/v) density resulted in the largest SC colony and myogenic potential after 4 days of culture. Finally, we further demonstrate that in vivo delivery of SC encapsulated within biofunctional hydrogel showed a significant improvement in transplantation efficiency compared to cells only controls. Collectively, these results illustrate a promising opportunity for the stem cell therapy for muscular dystrophy and aging. Support or Funding Information Petit Institute for Bioengineering and Bioscience, Center for Regenerative Engineering and Medicine, and American Federation of Aging Research