title: Effect of self-assembled peptide-mesenchymal stem cell complex on the progression of osteoarthritis in a rat model.
abstract: OBJECTIVE
  To evaluate the efficacy of mesenchymal stem cells (MSCs) encapsulated in self-assembled peptide (SAP) hydrogels in a rat knee model for the prevention of osteoarthritis (OA) progression.
  
  
  METHODS
  Nanostructured KLD-12 SAPs were used as the injectable hydrogels. Thirty-three Sprague Dawley rats were used for the OA model. Ten rats were used for the evaluation of biotin-tagged SAP disappearance. Twenty-three rats were divided into four groups: MSC (n=6), SAP (n=6), SAP-MSC (n=6), and no treatment (n=5). MSCs, SAPs, and SAP-MSCs were injected into the knee joints 3 weeks postsurgery. Histologic examination, immunofluorescent staining, measurement of cytokine levels, and micro-computed tomography analysis were conducted 6 weeks after injections. Behavioral studies were done to establish baseline measurements before treatment, and repeated 3 and 6 weeks after treatment to measure the efficacy of SAP-MSCs.
  
  
  RESULTS
  Concentration of biotinylated SAP at week 1 was not significantly different from those at week 3 and week 6 (P=0.565). Bone mineral density was significantly lower in SAP-MSC groups than controls (P=0.002). Significant differences in terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling staining between the control group and all other groups were observed. Caspase-8, tissue inhibitor of metalloproteinases 1, and matrix metalloproteinase 9 were diffusely stained in controls, whereas localized or minimal staining was observed in other groups. Modified Mankin scores were significantly lower in the SAP and SAP-MSC groups than in controls (P=0.001 and 0.013). Although not statistically significant, synovial inflammation scores were lower in the SAP (1.3±0.3) and SAP-MSC (1.3±0.2) groups than in controls (2.6±0.2). However, neither the cytokine level nor the behavioral score was significantly different between groups.
  
  
  CONCLUSIONS
  Injection of SAP-MSC hydrogels showed evidence of chondroprotection, as measured by the histologic grading and decreased expression of biochemical markers of inflammation and apoptosis. It also lowered subchondral bone mineral density, which can be increased by OA. This suggests that the SAP-MSC complex may have clinical potential to inhibit OA progression.
authors.affiliation: Biomaterials Research Center, Korea Institute of Science and Technology, Seoul, South Korea.
authors.forename: Ji Eun
authors.initials: JE
authors.lastname: Kim
authors.affiliation: Department of Physical and Rehabilitation Medicine, Samsung Medical Center, Seoul, South Korea.
authors.forename: Sang Mok
authors.initials: SM
authors.lastname: Lee
authors.affiliation: Biomaterials Research Center, Korea Institute of Science and Technology, Seoul, South Korea.
authors.forename: Soo Hyun
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Bioengineering, University of Washington, Seattle, WA, USA.
authors.forename: Phil
authors.initials: P
authors.lastname: Tatman
authors.affiliation: Department of Orthopaedics and Sports Medicine, University of Washington, Seattle, WA, USA.
authors.forename: Albert O
authors.initials: AO
authors.lastname: Gee
authors.affiliation: Department of Bioengineering, University of Washington, Seattle, WA, USA ; Institute for Stem Cell and Regenerative Medicine and Center for Cardiovascular Biology, University of Washington, Seattle, WA, USA.
authors.forename: Deok-Ho
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Advanced Analysis Center, Korea Institute of Science and Technology, Seoul, South Korea.
authors.forename: Kyung Eun
authors.initials: KE
authors.lastname: Lee
authors.affiliation: Biomaterials Research Center, Korea Institute of Science and Technology, Seoul, South Korea.
authors.forename: Youngmee
authors.initials: Y
authors.lastname: Jung
authors.affiliation: Department of Physical and Rehabilitation Medicine, Samsung Medical Center, Seoul, South Korea.
authors.forename: Sang Jun
authors.initials: SJ
authors.lastname: Kim
mesh_terms: D000818:Animals; D017209:Apoptosis; D001522:Behavior, Animal; D053181:Caspase 8 / Q000378:metabolism; D019902:Chondrocytes / Q000166:cytology; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D020370:Osteoarthritis, Knee / Q000000981:diagnostic imaging / Q000473:pathology* / Q000601:surgery*; D010455:Peptides / Q000737:chemistry*; D011859:Radiography; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D010455:Peptides; D053181:Caspase 8; D020780:Matrix Metalloproteinase 9
keywords: apoptosis; chondrogenesis; mesenchymal stem cell; osteoarthritis; self-assembled peptide