title: Safety Studies for Use of Adipose Tissue-Derived Mesenchymal Stromal/Stem Cells in a Rabbit Model for Osteoarthritis to Support a Phase I Clinical Trial.
abstract: Adipose-derived mesenchymal stem cells (AMSCs) offer potential as a therapeutic option for clinical applications in musculoskeletal regenerative medicine because of their immunomodulatory functions and capacity for trilineage differentiation. In preparation for a phase I clinical trial using AMSCs to treat patients with osteoarthritis, we carried out preclinical studies to assess the safety of human AMSCs within the intra-articular joint space. Culture-expanded human AMSCs grown in human platelet-lysate were delivered via intra-articular injections into normal healthy rabbit knees and knees at risk for the development of osteoarthritis after bilateral medial anterior hemimeniscectomy. Treatment outcomes and safety were evaluated by assessing the general health, function, and behavior of the animals. Joint tissues were analyzed by x-ray, magnetic resonance imaging, and histopathology. Intra-articular AMSC therapy was well tolerated in this study. We did not observe adverse systemic reactions, nor did we find evidence of damage to intra-articular joint tissues. Thus, the data generated in this study show a favorable safety profile for AMSCs within the joint space in support of a phase I clinical trial evaluating the clinical utility of AMSCs to treat osteoarthritis. Stem Cells Translational Medicine 2017;6:910-922.
authors.affiliation: Department of Orthopedic Surgery, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Riester
authors.affiliation: Department of Orthopedic Surgery, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Janet M
authors.initials: JM
authors.lastname: Denbeigh
authors.affiliation: Department of Orthopedic Surgery, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota, USA.|Department of Orthopedic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Department of Orthopedic Surgery, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota, USA.|Department of Biomedical Engineering and Physiology, Mayo Graduate School, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Dakota L
authors.initials: DL
authors.lastname: Jones
authors.affiliation: Department of Orthopedic Surgery, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Tristan
authors.initials: T
authors.lastname: de Mooij
authors.affiliation: Department of Orthopedic Surgery, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Lewallen
authors.affiliation: Department of Orthopedic Surgery, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Hai
authors.initials: H
authors.lastname: Nie
authors.affiliation: Department of Orthopedic Surgery, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Paradise
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Darcie J
authors.initials: DJ
authors.lastname: Radel
authors.affiliation: Department of Orthopedic Surgery, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Amel
authors.initials: A
authors.lastname: Dudakovic
authors.affiliation: Department of Orthopedic Surgery, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Emily T
authors.initials: ET
authors.lastname: Camilleri
authors.affiliation: Department of Health Sciences Research, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Dirk R
authors.initials: DR
authors.lastname: Larson
authors.affiliation: Department of Physical Medicine and Rehabilitation, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota, USA.|Department of Anesthesiology, Division of Pain Medicine, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Wenchun
authors.initials: W
authors.lastname: Qu
authors.affiliation: Department of Orthopedic Surgery, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Aaron J
authors.initials: AJ
authors.lastname: Krych
authors.affiliation: Department of Radiology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Frick
authors.affiliation: Department of Biochemistry, Rush University Medical Center, Chicago, Illinois, USA.|Department of Orthopedic Surgery, Rush University Medical Center, Chicago, Illinois, USA.|Section of Rheumatology, Department of Internal Medicine, Rush University Medical Center, Chicago, Illinois, USA.|Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois, USA.
authors.forename: Hee-Jeong
authors.initials: HJ
authors.lastname: Im
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Allan B
authors.initials: AB
authors.lastname: Dietz
authors.affiliation: Department of Physical Medicine and Rehabilitation, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota, USA.|Department of Radiology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota, USA.|Department of Anatomy, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Jay
authors.initials: J
authors.lastname: Smith
authors.affiliation: Department of Orthopedic Surgery, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota, USA.|Department of Biomedical Engineering and Physiology, Mayo Graduate School, Mayo Clinic, Rochester, Minnesota, USA.|Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Andre J
authors.initials: AJ
authors.lastname: van Wijnen
mesh_terms: D000818:Animals; D017321:Clinical Trials, Phase I as Topic; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007270:Injections, Intra-Articular; D008279:Magnetic Resonance Imaging; D000074403:Meniscectomy; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D020370:Osteoarthritis, Knee / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D011817:Rabbits; D012307:Risk Factors
keywords: Cell therapy; Osteoarthritis; Rabbit; Regenerative medicine; Stem cell; Transplant