title: Synthetic niche to modulate regenerative potential of MSCs and enhance skeletal muscle regeneration.
abstract: Severe injury to the skeletal muscle often results in the formation of scar tissue, leading to a decline in functional performance. Traditionally, tissue engineering strategies for muscle repair have focused on substrates that promote myogenic differentiation of transplanted cells. In the current study, the reported data indicates that mesenchymal stromal cells (MSCs) transplanted via porous alginate cryogels promote muscle regeneration by secreting bioactive factors that profoundly influence the function of muscle progenitor cells. These cellular functions, which include heightened resistance of muscle progenitor cells to apoptosis, migration to site of injury, and prevention of premature differentiation are highly desirable in the healing cascade after acute muscle trauma. Furthermore, stimulation of MSCs with recombinant growth factors IGF-1 and VEGF165 was found to significantly enhance their paracrine effects on muscle progenitor cells. Multifunctional alginate cryogels were then utilized as synthetic niches that facilitate local stimulation of seeded MSCs by providing a sustained release of growth factors. In a clinically relevant injury model, the modulation of MSC paracrine signaling via engineered niches significantly improved muscle function by remodeling scar tissue and promoting the formation of new myofibers, outperforming standalone cell or growth factor delivery.
authors.affiliation: Julius Wolff Institute, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; Berlin-Brandenburg Center for Regenerative Therapies & Berlin-Brandenburg School for Regenerative Therapies, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; Center for Musculoskeletal Surgery, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Pumberger
authors.affiliation: Julius Wolff Institute, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; Berlin-Brandenburg Center for Regenerative Therapies & Berlin-Brandenburg School for Regenerative Therapies, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: Taimoor H
authors.initials: TH
authors.lastname: Qazi
authors.affiliation: Julius Wolff Institute, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: M Christine
authors.initials: MC
authors.lastname: Ehrentraut
authors.affiliation: Julius Wolff Institute, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; Berlin-Brandenburg Center for Regenerative Therapies & Berlin-Brandenburg School for Regenerative Therapies, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; Center for Musculoskeletal Surgery, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Textor
authors.affiliation: Julius Wolff Institute, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: Janina
authors.initials: J
authors.lastname: Kueper
authors.affiliation: Institute of Cell Biology and Neurobiology, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Gisela
authors.initials: G
authors.lastname: Stoltenburg-Didinger
authors.affiliation: Julius Wolff Institute, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; Berlin-Brandenburg Center for Regenerative Therapies & Berlin-Brandenburg School for Regenerative Therapies, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; Center for Musculoskeletal Surgery, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Winkler
authors.affiliation: Julius Wolff Institute, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; Berlin-Brandenburg Center for Regenerative Therapies & Berlin-Brandenburg School for Regenerative Therapies, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; Center for Musculoskeletal Surgery, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: von Roth
authors.affiliation: Julius Wolff Institute, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; Berlin-Brandenburg Center for Regenerative Therapies & Berlin-Brandenburg School for Regenerative Therapies, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; Center for Musculoskeletal Surgery, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Reinke
authors.affiliation: Berlin-Brandenburg Center for Regenerative Therapies & Berlin-Brandenburg School for Regenerative Therapies, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; Wyss Institute for Biologically Inspired Engineering, Harvard University, 3 Blackfan Cir., Boston, MA 02115, USA; John A. Paulson School of Engineering and Applied Sciences, Harvard University, 29 Oxford St., Cambridge, MA 02138, USA.
authors.forename: Cristina
authors.initials: C
authors.lastname: Borselli
authors.affiliation: Julius Wolff Institute, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; Berlin-Brandenburg Center for Regenerative Therapies & Berlin-Brandenburg School for Regenerative Therapies, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; Center for Musculoskeletal Surgery, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Perka
authors.affiliation: Berlin-Brandenburg Center for Regenerative Therapies & Berlin-Brandenburg School for Regenerative Therapies, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; Wyss Institute for Biologically Inspired Engineering, Harvard University, 3 Blackfan Cir., Boston, MA 02115, USA; John A. Paulson School of Engineering and Applied Sciences, Harvard University, 29 Oxford St., Cambridge, MA 02138, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Mooney
authors.affiliation: Julius Wolff Institute, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; Berlin-Brandenburg Center for Regenerative Therapies & Berlin-Brandenburg School for Regenerative Therapies, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; Center for Musculoskeletal Surgery, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; Wyss Institute for Biologically Inspired Engineering, Harvard University, 3 Blackfan Cir., Boston, MA 02115, USA; John A. Paulson School of Engineering and Applied Sciences, Harvard University, 29 Oxford St., Cambridge, MA 02138, USA.
authors.forename: Georg N
authors.initials: GN
authors.lastname: Duda
authors.affiliation: Julius Wolff Institute, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; Berlin-Brandenburg Center for Regenerative Therapies & Berlin-Brandenburg School for Regenerative Therapies, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; Center for Musculoskeletal Surgery, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany. Electronic address: Sven.Geissler@charite.de.
authors.forename: Sven
authors.initials: S
authors.lastname: Geißler
mesh_terms: D000818:Animals; D017209:Apoptosis; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D002460:Cell Line; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D055595:Mechanical Phenomena; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000502:physiology*; D017207:Rats, Sprague-Dawley; D012038:Regeneration; D023822:Tissue Engineering; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology*
chemical_list: C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D007334:Insulin-Like Growth Factor I
keywords: Biomaterial based stem cell niche; Engineered cell microenvironments; Muscle regeneration; Trophic factor secretion