title: Implantation of Stromal Vascular Fraction Progenitors at Bone Fracture Sites: From a Rat Model to a First-in-Man Study.
abstract: Stromal Vascular Fraction (SVF) cells freshly isolated from adipose tissue include osteogenic- and vascular-progenitors, yet their relevance in bone fracture healing is currently unknown. Here, we investigated whether human SVF cells directly contribute to the repair of experimental fractures in nude rats, and explored the feasibility/safety of their clinical use for augmentation of upper arm fractures in elderly individuals. Human SVF cells were loaded onto ceramic granules within fibrin gel and implanted in critical nude rat femoral fractures after locking-plate osteosynthesis, with cell-free grafts as control. After 8 weeks, only SVF-treated fractures did not fail mechanically and displayed formation of ossicles at the repair site, with vascular and bone structures formed by human cells. The same materials combined with autologous SVF cells were then used to treat low-energy proximal humeral fractures in 8 patients (64-84 years old) along with standard open reduction and internal fixation. Graft manufacturing and implantation were compatible with intraoperative settings and led to no adverse reactions, thereby verifying feasibility/safety. Biopsies of the repair tissue after up to 12 months, upon plate revision or removal, demonstrated formation of bone ossicles, structurally disconnected and morphologically distinct from osteoconducted bone, suggesting the osteogenic nature of implanted SVF cells. We demonstrate that SVF cells, without expansion or exogenous priming, can spontaneously form bone tissue and vessel structures within a fracture-microenvironment. The gained clinical insights into the biological functionality of the grafts, combined with their facile, intra-operative manufacturing modality, warrant further tests of effectiveness in larger, controlled trials. Stem Cells 2016;34:2956-2966.
authors.affiliation: Clinic of Traumatology, University Hospital Basel, University of Basel, Basel, Switzerland.|Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland.
authors.forename: Franziska
authors.initials: F
authors.lastname: Saxer
authors.affiliation: Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Scherberich
authors.affiliation: Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland.
authors.forename: Atanas
authors.initials: A
authors.lastname: Todorov
authors.affiliation: Clinic of Traumatology, University Hospital Basel, University of Basel, Basel, Switzerland.
authors.forename: Patrick
authors.initials: P
authors.lastname: Studer
authors.affiliation: Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Miot
authors.affiliation: Clinic of Traumatology, University Hospital Basel, University of Basel, Basel, Switzerland.
authors.forename: Simone
authors.initials: S
authors.lastname: Schreiner
authors.affiliation: Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland.
authors.forename: Sinan
authors.initials: S
authors.lastname: Güven
authors.affiliation: Clinic of Plastic, Reconstructive and Aesthetic Surgery, University Hospital Basel, Basel, Switzerland.
authors.forename: Laurent A H
authors.initials: LA
authors.lastname: Tchang
authors.affiliation: Clinic of Plastic, Reconstructive and Aesthetic Surgery, University Hospital Basel, Basel, Switzerland.
authors.forename: Martin
authors.initials: M
authors.lastname: Haug
authors.affiliation: Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Heberer
authors.affiliation: Clinic of Plastic, Reconstructive and Aesthetic Surgery, University Hospital Basel, Basel, Switzerland.
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: Schaefer
authors.affiliation: Clinic of Traumatology, University Hospital Basel, University of Basel, Basel, Switzerland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Rikli
authors.affiliation: Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland.
authors.forename: Ivan
authors.initials: I
authors.lastname: Martin
authors.affiliation: Clinic of Traumatology, University Hospital Basel, University of Basel, Basel, Switzerland.
authors.forename: Marcel
authors.initials: M
authors.lastname: Jakob
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D003710:Demography; D004195:Disease Models, Animal; D005260:Female; D005269:Femur / Q000000981:diagnostic imaging / Q000473:pathology; D005500:Follow-Up Studies; D050723:Fractures, Bone / Q000000981:diagnostic imaging / Q000473:pathology* / Q000628:therapy; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010012:Osteogenesis; D010147:Pain Measurement; D051381:Rats; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology*; D017154:Stromal Cells / Q000637:transplantation
keywords: Adipose tissue; Bone repair; Cellular therapy; Mesenchymal stromal cells; Osteoporotic fracture