AIM: The therapeutic potential of adipose-derived stem cell conditioned medium (ASC-CM) was studied in the rabbit model of critical limb ischemia (CLI). METHODS: Rabbits received treatment with ASC-CM or placebo. Gastrocnemius muscle tissue was collected 35 days after ischemia induction. Ischemic changes were evaluated in hematoxylin-eosin stained tissues for early (necrotic lesions/granulation tissue) and late (fibrous scars) phases of tissue repair. The expression of proangiogenic miR-126 was also evaluated using in situ hybridization. The levels of cytokines, insulin, and C-peptide were measured in blood. RESULTS: Early repair phases were observed more often in placebo-treated samples (45.5%) than in ASC-CM-treated ones (22.2%). However, the difference was not statistically significant. We demonstrated a statistically significant positive correlation between the early healing phases in tissue samples and C-peptide levels in peripheral blood. The expression of proangiogenic miR-126 was also shown in a number of structures in all phases of ischemic tissue healing. CONCLUSION: Based on our results, we believe that treatment with ASC-CM has the potential to accelerate the healing process in ischemic tissues in the rabbit model of CLI. The whole healing process was accompanied by miR-126 tissue expression. C-peptide could be used to monitor the course of the tissue healing process.

• MeSH
• C-peptid krev   MeSH
• cytokiny krev   MeSH
• diabetická noha MeSH
• dospělí MeSH
• experimentální diabetes mellitus krev   MeSH
• fibróza MeSH
• fyziologická neovaskularizace účinky léků   MeSH
• granulační tkáň patologie   MeSH
• hojení ran účinky léků   fyziologie   MeSH
• hybridizace in situ MeSH
• inzulin krev   MeSH
• ischemie krev   MeSH
• jizva patologie   MeSH
• kosterní svaly krevní zásobení   účinky léků   patologie   MeSH
• králíci MeSH
• kultivační média speciální farmakologie   MeSH
• lidé MeSH
• mezenchymální kmenové buňky * MeSH
• mikro RNA metabolismus   MeSH
• modely nemocí na zvířatech MeSH
• nekróza MeSH
• zadní končetina MeSH
• zvířata MeSH
• Check Tag
• dospělí MeSH
• králíci MeSH
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

• Klíčová slova
• kontingenční tabulky,
• MeSH
• kontinuální vzdělávání * statistika a číselné údaje   MeSH
• lidé MeSH
• neparametrická statistika MeSH
• personál nemocniční výchova   MeSH
• postoj zdravotnického personálu MeSH
• pracovní uspokojení MeSH
• průzkumy a dotazníky MeSH
• řízení nemocnice MeSH
• rozdělení chí kvadrát MeSH
• statistika jako téma MeSH
• Check Tag
• lidé MeSH

BACKGROUND Paracrine factors secreted by adipose-derived stem cells can be captured, fractionated, and concentrated to produce therapeutic factor concentrate (TFC). The present study examined whether TFC effects could be enhanced by combining TFC with a biological matrix to provide sustained release of factors in the target region. MATERIAL AND METHODS Unilateral hind limb ischemia was induced in rabbits. Ischemic limbs were injected with either placebo control, TFC, micronized small intestinal submucosa tissue (SIS), or TFC absorbed to SIS. Blood flow in both limbs was assessed with laser Doppler perfusion imaging. Tissues harvested at Day 48 were assessed immunohistochemically for vessel density; in situ hybridization and quantitative real-time PCR were employed to determine miR-126 expression. RESULTS LDP ratios were significantly elevated, compared to placebo control, on day 28 in all treatment groups (p=0.0816, p=0.0543, p=0.0639, for groups 2-4, respectively) and on day 36 in the TFC group (p=0.0866). This effect correlated with capillary density in the SIS and TFC+SIS groups (p=0.0093 and p=0.0054, respectively, compared to placebo). A correlation was observed between miR-126 levels and LDP levels at 48 days in SIS and TFC+SIS groups. CONCLUSIONS A single bolus administration of TFC and SIS had early, transient effects on reperfusion and promotion of ischemia repair. The effects were not additive. We also discovered that TFC modulated miR-126 levels that were expressed in cell types other than endothelial cells. These data suggested that TFC, alone or in combination with SIS, may be a potent therapy for patients with CLI that are at risk of amputation.

• MeSH
• extracelulární matrix metabolismus   MeSH
• ischemie genetika   patologie   terapie   MeSH
• kmenové buňky cytologie   MeSH
• končetiny krevní zásobení   patologie   MeSH
• králíci MeSH
• kůže patologie   MeSH
• laser doppler flowmetrie MeSH
• lidé středního věku MeSH
• lidé MeSH
• mikro RNA genetika   metabolismus   MeSH
• mikropartikule metabolismus   MeSH
• modely nemocí na zvířatech MeSH
• perfuze MeSH
• regulace genové exprese MeSH
• reperfuzní poškození patologie   terapie   MeSH
• střevní sliznice fyziologie   MeSH
• tenké střevo fyziologie   MeSH
• transplantace kmenových buněk * MeSH
• tuková tkáň cytologie   MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH