title: Therapeutic potential of adipose-derived stromal cells in age-related osteoporosis.
abstract: Adipose-derived stromal cells (ASCs) are increasingly being used for orthopedic-based tissue engineering approaches due to their ability to readily undergo osteogenic differentiation. In the present study, we used in vitro and in vivo approaches to evaluate the use of ASCs as a treatment strategy for age-related osteoporosis. Molecular, histological and micro-computed tomography (micro-CT) based approaches confirmed that ASCs isolated from 18-week-old osteoporotic senescence-accelerated mice (SAMP6) were capable of undergoing osteogenesis when cultured in either silk fibroin (SF) scaffolds or scaffold-free microtissues (ASC-MT). A single intratibial injection of CM-Dil-labeled isogeneic ASCs or ASC-MT into SAMP6 recipients significantly improved trabecular bone quality after 6 weeks in comparison to untreated contralateral bones, as determined by micro-CT. Injected ASCs could be observed in paraffin wax bone sections at 24 h and 6 weeks post treatment and induced a significant increase in several molecular markers of bone turnover. Furthermore, a significant improvement in the osteogenic potential of osteoporotic patient-derived human bone marrow stromal cells (BMSCs) was observed when differentiated in conditioned culture media harvested from osteoporotic patient-derived human ASCs. These findings therefore support the use of ASCs as an autologous cell-based approach for the treatment of osteoporosis.
authors.affiliation: Bone and Stem Cell Research Group, CABMM, University of Zurich, 8057 Zurich, Switzerland; Institute of Physiology and Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, 8057 Zurich, Switzerland.
authors.forename: Ali
authors.initials: A
authors.lastname: Mirsaidi
authors.affiliation: Department of Trauma Surgery and Sports Medicine, Innsbruck Medical University, A-6020 Innsbruck, Austria.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Genelin
authors.affiliation: Institute for Biomechanics, ETH Zurich, 8093 Zurich, Switzerland.
authors.forename: Jolanda R
authors.initials: JR
authors.lastname: Vetsch
authors.affiliation: Institute for Biomechanics, ETH Zurich, 8093 Zurich, Switzerland.
authors.forename: Scott
authors.initials: S
authors.lastname: Stanger
authors.affiliation: Musculoskeletal Research Unit, CABMM, University of Zurich, 8057 Zurich, Switzerland.
authors.forename: Felix
authors.initials: F
authors.lastname: Theiss
authors.affiliation: Department of Trauma Surgery and Sports Medicine, Innsbruck Medical University, A-6020 Innsbruck, Austria.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Lindtner
authors.affiliation: Musculoskeletal Research Unit, CABMM, University of Zurich, 8057 Zurich, Switzerland.
authors.forename: Brigitte
authors.initials: B
authors.lastname: von Rechenberg
authors.affiliation: Department of Trauma Surgery and Sports Medicine, Innsbruck Medical University, A-6020 Innsbruck, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Blauth
authors.affiliation: Institute for Biomechanics, ETH Zurich, 8093 Zurich, Switzerland.
authors.forename: Ralph
authors.initials: R
authors.lastname: Müller
authors.affiliation: Institute for Biomechanics, ETH Zurich, 8093 Zurich, Switzerland.
authors.forename: Gisela A
authors.initials: GA
authors.lastname: Kuhn
authors.affiliation: Institute for Biomechanics, ETH Zurich, 8093 Zurich, Switzerland; Department of Biomedical Engineering, Eindhoven University of Technology, P.O. Box 513, 5600 MB Eindhoven, The Netherlands; Institute for Complex Molecular Systems, Eindhoven University of Technology, P.O. Box 513, Eindhoven 5600 MB, The Netherlands.
authors.forename: Sandra
authors.initials: S
authors.lastname: Hofmann Boss
authors.affiliation: Department of Trauma Surgery and Sports Medicine, Innsbruck Medical University, A-6020 Innsbruck, Austria.
authors.forename: Hannes L
authors.initials: HL
authors.lastname: Ebner
authors.affiliation: Bone and Stem Cell Research Group, CABMM, University of Zurich, 8057 Zurich, Switzerland; Institute of Physiology and Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, 8057 Zurich, Switzerland. Electronic address: peter.richards@cabmm.uzh.ch.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Richards
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000367:Age Factors; D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology; D051379:Mice; D010012:Osteogenesis; D010024:Osteoporosis / Q000453:epidemiology / Q000473:pathology / Q000628:therapy*; D017154:Stromal Cells / Q000166:cytology / Q000637:transplantation*; D013977:Tibia / Q000166:cytology / Q000473:pathology
keywords: Bone regeneration; Osteogenesis; Osteoporosis; Stem cell; Transplantation