title: Enhanced Expansion and Sustained Inductive Function of Skin-Derived Precursor Cells in Computer-Controlled Stirred Suspension Bioreactors.
abstract: Endogenous dermal stem cells (DSCs) reside in the adult hair follicle mesenchyme and can be isolated and grown in vitro as self-renewing colonies called skin-derived precursors (SKPs). Following transplantation into skin, SKPs can generate new dermis and reconstitute the dermal papilla and connective tissue sheath, suggesting they could have important therapeutic value for the treatment of skin disease (alopecia) or injury. Controlled cell culture processes must be developed to efficiently and safely generate sufficient stem cell numbers for clinical use. Compared with static culture, stirred-suspension bioreactors generated fivefold greater expansion of viable SKPs. SKPs from each condition were able to repopulate the dermal stem cell niche within established hair follicles. Both conditions were also capable of inducing de novo hair follicle formation and exhibited bipotency, reconstituting the dermal papilla and connective tissue sheath, although the efficiency was significantly reduced in bioreactor-expanded SKPs compared with static conditions. We conclude that automated bioreactor processing could be used to efficiently generate large numbers of autologous DSCs while maintaining their inherent regenerative function. Stem Cells Translational Medicine 2017;6:434-443.
authors.affiliation: Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Natacha A
authors.initials: NA
authors.lastname: Agabalyan
authors.affiliation: Pharmaceutical Production Research Facility, Schulich School of Engineering, University of Calgary, Calgary, Alberta, Canada.|Department of Chemical and Petroleum Engineering, Schulich School of Engineering, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Breanna S
authors.initials: BS
authors.lastname: Borys
authors.affiliation: Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Holly D
authors.initials: HD
authors.lastname: Sparks
authors.affiliation: Pharmaceutical Production Research Facility, Schulich School of Engineering, University of Calgary, Calgary, Alberta, Canada.|Biomedical Engineering Graduate Program, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Boon
authors.affiliation: Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Eko W
authors.initials: EW
authors.lastname: Raharjo
authors.affiliation: Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Sepideh
authors.initials: S
authors.lastname: Abbasi
authors.affiliation: Pharmaceutical Production Research Facility, Schulich School of Engineering, University of Calgary, Calgary, Alberta, Canada.|Department of Chemical and Petroleum Engineering, Schulich School of Engineering, University of Calgary, Calgary, Alberta, Canada.|Biomedical Engineering Graduate Program, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Kallos
authors.affiliation: Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary, Alberta, Canada.|Alberta Children's Hospital Research Institute, Calgary, Alberta, Canada.|Hotchkiss Brain Institute, Calgary, Alberta, Canada.
authors.forename: Jeff
authors.initials: J
authors.lastname: Biernaskie
mesh_terms: D000818:Animals; D019149:Bioreactors; D018929:Cell Culture Techniques / Q000295:instrumentation*; D049109:Cell Proliferation; D002469:Cell Separation; D002478:Cells, Cultured; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D018859:Hair Follicle / Q000166:cytology*; D007700:Kinetics; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000502:physiology*; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D010641:Phenotype; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D044968:Regenerative Medicine / Q000295:instrumentation* / Q000379:methods; D055153:Stem Cell Niche
chemical_list: D049452:Green Fluorescent Proteins
keywords: Bioprocess engineering; Dermal stem cells; Hair follicle; Mesenchyme; Regeneration; Scale-up