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

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.

Insight on stem cell preconditioning and instructive biomaterials to enhance cell adhesion, retention, and engraftment for tissue repair

“…Self-assembling peptides. Self-assembling peptides (SAPs) are also attractive candidates as cell carriers and have been reported to enhance the survival and differentiation of transplanted cells [248][249][250][251][252][253]. SAPs consist of alternating hydrophilic and hydrophobic residues and form nanofibers at physiological pH or salt concentrations.…”

Therapeutic effects of neuropeptide substance P coupled with self-assembled peptide nanofibers on the progression of osteoarthritis in a rat model

“…The items of the scoring system were the cartilage structure, cartilage cells, Alcian blue staining, and tidemark integrity. A detailed description is given in a previous article [37].…”

“…In an open field acrylic box in which the floor was covered with foam stamp pads, and the 4 sides were covered with white paper, a rat touched the walls of the box with their fore limbs stained with ink from the foam stamp pads and the number of touches above 5 cm from the bottom of the paper was counted (n=3, 4). The method in detail is described elsewhere [37,38].…”

A Rabbit Model of Acanthamoeba Keratitis That Better Reflects the Natural Human Infection

“…The development of an appropriate animal model is essential for detailed study of molecular biology, pathology and immunology of AK and for control of in vivo testing of new pharmacologic agents (Siddiqui et al, 2012). An ideal model of AK should parallel the course of the disease in humans (Vasseneix et al, 2006;Ren et al, 2010;Kim et al, 2014). For example, an animal model should permit evaluation of the role of ocular trauma and coinfection with bacteria in AK, and facilitate investigations exploring the pathophysiology, cell biology, genetics, immunology, and therapy for this disease (He et al, 1992).…”

“…Most animals infected by intrastromal injection of Acanthamoeba may develop severe endophthalmitis, and even death can occur (Ren et al, 2010). In previous studies, pigs, mice, rats, and rabbits have been used as animal models to produce AK (Vasseneix et al, 2006;Ren et al, 2010;Kim et al, 2014;Kemp et al, 2014). Rabbits are preferred as keratitis models because the rabbit cornea is more similar to the human cornea (Zhou et al, 2014;Karn et al, 2014;Hayes et al, 2007).…”