Adipose-Derived Stem Cells Improve Collagenase-Induced Tendinopathy in a Rat Model.

BACKGROUND: Tendinopathy is a common and highly prevalent musculoskeletal disorder characterized by repetitive activity-related pain and focal tendon tenderness. Histopathologically, tendinopathic tissue mainly shows degenerative changes. Therefore, tendinopathy is not affected by anti-inflammatory therapies. A novel approach, including a stem cell-based therapy, may be beneficial for its treatment. PURPOSE/HYPOTHESIS: The purpose of this study was to evaluate the effects of adipose-derived stem cells (ASCs) on tendon healing in a rat tendinopathy model. The hypothesis was that ASC transplantation would improve degeneration in collagenase-induced tendinopathy. STUDY DESIGN: Controlled laboratory study. METHODS: Sixteen F344/NSlc rats underwent collagenase injection into the Achilles tendon to induce tendinopathy. At 1 week after collagenase injection, 8 rats received ASCs (ASC group) and 8 received phosphate-buffered saline alone (PBS group). Animals were sacrificed at 4 or 12 weeks after ASC administration, and the degree of degeneration in each tendon was histologically evaluated according to the Bonar scale. The microstructure of healing tendons was observed by scanning electron microscopy. Reverse-transcription polymerase chain reaction (RT-PCR) was performed to measure the ratio of type III collagen messenger RNA (mRNA) to type I collagen mRNA in tendons. RESULTS: The median Bonar scale score in the ASC and PBS groups was 2.5 and 5.33 at 4 weeks after treatment and 1.0 and 4.0 at 12 weeks after treatment, respectively. Histologically, the ASC group showed a significantly lower degree of tendon degeneration than the PBS group at both time points. In the RT-PCR analysis, the ratio of type III collagen to type I collagen was significantly lower in the ASC group than in the PBS group at 12 weeks after treatment. Moreover, this ratio decreased over time in the ASC group, whereas it increased over time in the PBS group. CONCLUSION: The study findings demonstrate that the application of ASCs results in significant improvement in the pathological findings associated with tendinopathy and the normalization of collagen ratios within the affected tendon. CLINICAL RELEVANCE: Subcutaneous adipose tissue can be harvested easily, and ASC administration might have the potential to rapidly treat tendinopathy.

Coadministration of adipose-derived stem cells and control-released basic fibroblast growth factor facilitates angiogenesis in a murine ischemic hind limb model.

OBJECTIVE: Adipose-derived stem cells (ASCs) have angiogenic potential owing to their differentiation into endothelial cells and their release of angiogenic growth factors to elicit paracrine effects. In addition, control-released basic fibroblast growth factor (bFGF) sustained with a gelatin hydrogel also supports effective angiogenesis. We sought to determine if coadministration of ASCs and control-released bFGF into murine ischemic limbs facilitates angiogenesis. METHODS: Levels of growth factors in the conditioned media of ASCs cultured with or without control-released bFGF were measured by enzyme-linked immunosorbent assays. A murine ischemic hind limb model was generated and intramuscularly injected with the following: gelatin hydrogel (group 1), a high number of ASCs (group 2), control-released bFGF (group 3), a small number of ASCs and control-released bFGF (group 4), and a high number of ASCs and control-released bFGF (group 5). Macroscopic and microscopic vascular changes were evaluated until day 7 by laser Doppler perfusion imaging and histologic analyses, respectively. RESULTS: Secretion of hepatocyte growth factor, vascular endothelial growth factor, and transforming growth factor-ß1 was enhanced by control-released bFGF. Vascular improvement was achieved in groups 4 and 5 according to laser Doppler perfusion imaging. Hematoxylin and eosin staining and CD31 immunohistochemical staining demonstrated an increase in the vascular density, vessel diameter, and thickness of vessel walls in groups 4 and 5. Cells positively stained for CD146, α-smooth muscle actin, and transforming growth factor-ß1 were observed around vessel walls in groups 4 and 5. CONCLUSIONS: These findings suggest that coadministration of ASCs and control-released bFGF facilitates angiogenesis in terms of vessel maturation in a murine ischemic hind limb model.

Two-year visual results for older Asian women treated with photodynamic therapy or bevacizumab for myopic choroidal neovascularization.

PURPOSE: To compare the long-term visual and anatomic outcome of treatment with photodynamic therapy (PDT) or intravitreal bevacizumab (IVB; Avastin; Genentech Inc, South San Francisco, California, USA) for choroidal neovascularization attributable to pathologic myopia (mCNV). DESIGN: An open-label, interventional case series. SETTING: Multi-institutional. PATIENTS: Thirty-one eyes of Japanese women who received either PDT or IVB for mCNV. Inclusion criteria were age 50 years or older, greatest linear dimension (GLD) 1200 to 3000 microm, and baseline best-corrected visual acuity (BCVA) 20/200 to 20/40. INTERVENTION PROCEDURES: Patients received either PDT or IVB (1 mg/40 microL) throughout the study, with re-treatment when necessary. MAIN OUTCOME MEASURES: BCVA and visual gain/loss at 3, 6, 12, 18, and 24 months after the initial treatment. RESULTS: Age, BCVA, location of CNV, refractive error, and symptom duration at baseline did not differ significantly between groups. BCVA was significantly improved at 3 to 12 months (P < .05); however, the significance was lost at 18 and 24 months in the IVB group. The PDT group showed no significant improvement within the first year, and vision slowly worsened after 12 months, becoming significantly worse at 18 and 24 months compared to baseline (P< .01). BCVA was significantly higher in the IVB group at 6 months (P< .05), and 12 months or further (P < .01). Visual gain was significantly greater in the IVB group at 6, 12, 18, and 24 months (P < .05 for 6, 18, and 24 months and P < .01 for 12 months). CONCLUSIONS: These findings indicate that the effects of PDT and IVB have a different time course, and that IVB provides a significantly better BCVA than PDT for mCNV over the long-term.