The Use of Umbilical Cord-derived Mesenchymal Stem Cells Seeded Fibrin Matrix in the Treatment of Stage IV Acute Graft-Versus-Host Disease Skin Lesions in Pediatric Hematopoietic Stem Cell Transplant Patients.

Mesenchymal stem cells (MSCs) have been used systemically or locally in many chronic and nonhealing skin lesions in recent years. In this study, umbilical cord-derived MSCs (UC-MSCs)-seeded fibrin matrix was used as a wound dressing in pediatric patients with stage 4 acute graft-versus-host disease (aGVHD)-induced desquamated skin lesions. This is the first study in which the UC-MSCs-seeded fibrin matrix was used as a wound dressing in aGVHD. A total of 14 times the MSCs-seeded fibrin matrix were applied to 9 patients as a wound dressing. On the seventh day, epithelialization and clinical response were evaluated. According to the size of the skin defect min: 1, max: 6 pieces were applied at a time. After 48 to 72 hours, it was observed that all of the MSCs-seeded fibrin matrixes adhered to the skin and the crustation started in 6 (43%) applications, whereas liquefaction was detected under all of them in 7 (50%) applications. Complete response was obtained in 6 applications (43%), partial response in 1 (7%), and no response in 7 applications (50%). This study showed that the MSCs-seeded fibrin matrix can be used effectively and safely in the matrix in the local treatment of aGVHD-induced skin wounds in pediatric patients.

Anticancer activity of Schiff base-Poloxamer P85 combination against kidney cancer.

PURPOSE: Renal cell carcinoma (RCC) accounts for approximately 80% of the primary renal cancers, and current treatment strategies are not sufficient to provide a certain solution. Since there are not many treatment options, interest in discovery of alternative drugs has increased. METHODS: In the current study, anticancer activity of a novel heterodinuclear Cu(II)-Mn(II) complex (Schiff base-SB) in combination with poly(ethylene oxide) and poly(propylene oxide) block copolymer (pluronic) P85 was tested against RCC. Cell viability, apoptosis and gene expression analysis were conducted in vitro by using Renca cells. RESULTS: The results revealed that the SB-P85 combination decreased cell proliferation by increasing the apoptotic gene expressions and apoptosis. Renca-injected BALB/c mice were used to mimic early stage of RCC model. Treatment with SB-P85 combination suppressed tumor formation and growth compared to baseline. CONCLUSION: Overall, SB-P85 showed promising anticancer activity against RCC in vitro and in vivo.

In vivo tissue-engineered allogenic trachea transplantation in rabbits: a preliminary report.

Conventional tracheal reconstruction techniques are not successful at restoring functional units in situations with extensive damage involving more than half the length of the trachea. For the first time, we investigated in vivo tissue-engineered trachea regeneration from a decellularized cadaveric trachea matrix with seeded adult adipose tissue-derived mesenchymal stem cells (MSCs) and investigated the integration of the matrix into the recipient tracheal side. For the procedure, 1.8-cm grafts were prepared from 3.5-cm tracheas of three donor rabbits. Then, tracheal grafts were rendered nonimmunogenic using a decellularization technique. MSCs isolated from recipient rabbit adipose tissue were cultured and marked before being seeded in the decellularized matrix. A total of 1.8 cm of the recipient tracheas was replaced with either a decellularized tracheal matrix (group 1) or tracheal matrix-seeded MSCs (group 2). Rabbits survived 17 ± 2 days in the first group, and the causes of death were separation in the anastomosis region, airway obstruction, and infection. In the second group, animals were sacrificed on the 30th, 60th, and 90th days of follow-up. Histopathological analysis revealed the integration of MSCs seeded-decellularized cadaveric tracheas to the recipient tracheal sides and increased angiogenesis. The MSCs were traced by fluorescence microscopy in the ciliated epithelium, under the epithelium, and in the cartilage of the integrated new trachea. Tracheas generated by autologous cells and tissue-engineering techniques will be a great source for the treatment of life-threatening tracheal injuries after the completion of related studies.

Injectable tissue-engineered cartilage using commercially available fibrin glue.

OBJECTIVES/HYPOTHESIS: To achieve injectable tissue-engineered cartilage using a commercially available fibrin sealant, and to determine the most suitable fibrin glue concentration, cartilage source, and cultured chondrocyte concentration. STUDY DESIGN: Animal research. METHODS: A total of 28 immunocompetent New Zealand white rabbits were divided into four groups. The cultured chondrocytes from different anatomical sources carried in fibrin glue with and without aprotinin in different concentrations of fibrinogen and thrombin (Tisseell), were injected into forehead and interocular regions of the rabbits. The new tissue formation was harvested at 8 weeks and analyzed through gross and histological analysis. RESULTS: The new tissue formations were found in round, elliptical, and flat forms. The mean value of Tisseell and cell suspension was 0.8 cc in all of the rabbits' injection regions, but the mean volume of the samples in which immature cartilage matrix and mature cartilage was 0.1 cc. In the 20 of the 55 injection regions of rabbits (36, 36%), mature and/or immature cartilage formation were observed. We observed inflammatory reactions, abscess formation, and foreign body reactions around the new cartilage tissue of tissue-engineered cartilage. The comparison of results using different cartilage sources, chondrocyte concentrations, or different fibrin glue concentrations did not show any significant difference. CONCLUSIONS: We observed that changing the concentrations of ingredients of commercially available fibrin glue, the source of the cartilage, or the cultured chondrocyte concentration did not have significant effect on neocartilage formation.