Effect of self-assembled peptide-mesenchymal stem cell complex on the progression of osteoarthritis in a rat model

Ji Eun Kim, Sang Mok Lee, Soo Hyun Kim, Phil Tatman, Albert O. Gee, Deok Ho Kim, Kyung Eun Lee, Youngmee Jung, Sang Jun Kim

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Purpose: 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. Materials and 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. Conclusion: 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.

Original languageEnglish
Pages (from-to)141-157
Number of pages17
JournalInternational Journal of Nanomedicine
Volume9
Issue numberSUPPL.1
DOIs
Publication statusPublished - 2014 May 7
Externally publishedYes

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Stem cells
Mesenchymal Stromal Cells
Osteoarthritis
Peptides
Rats
Hydrogels
Control Groups
Staining and Labeling
Bone Density
Injections
Minerals
Bone
Cytokines
Inflammation
Tissue Inhibitor of Metalloproteinase-1
DNA Nucleotidylexotransferase
Caspase 8
Nanostructures
Matrix Metalloproteinase 9
Cell death

Keywords

  • Apoptosis
  • Chondrogenesis
  • Mesenchymal stem cell
  • Osteoarthritis
  • Self-assembled peptide

ASJC Scopus subject areas

  • Bioengineering
  • Biomaterials
  • Organic Chemistry
  • Drug Discovery
  • Biophysics

Cite this

Effect of self-assembled peptide-mesenchymal stem cell complex on the progression of osteoarthritis in a rat model. / Kim, Ji Eun; Lee, Sang Mok; Kim, Soo Hyun; Tatman, Phil; Gee, Albert O.; Kim, Deok Ho; Lee, Kyung Eun; Jung, Youngmee; Kim, Sang Jun.

In: International Journal of Nanomedicine, Vol. 9, No. SUPPL.1, 07.05.2014, p. 141-157.

Research output: Contribution to journalArticle

Kim, JE, Lee, SM, Kim, SH, Tatman, P, Gee, AO, Kim, DH, Lee, KE, Jung, Y & Kim, SJ 2014, 'Effect of self-assembled peptide-mesenchymal stem cell complex on the progression of osteoarthritis in a rat model', International Journal of Nanomedicine, vol. 9, no. SUPPL.1, pp. 141-157. https://doi.org/10.2147/IJN.S54114
Kim, Ji Eun ; Lee, Sang Mok ; Kim, Soo Hyun ; Tatman, Phil ; Gee, Albert O. ; Kim, Deok Ho ; Lee, Kyung Eun ; Jung, Youngmee ; Kim, Sang Jun. / Effect of self-assembled peptide-mesenchymal stem cell complex on the progression of osteoarthritis in a rat model. In: International Journal of Nanomedicine. 2014 ; Vol. 9, No. SUPPL.1. pp. 141-157.
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AU - Kim, Deok Ho

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N2 - Purpose: 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. Materials and 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. Conclusion: 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.

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