Background There is not an ideal biomaterial for tissue-engineered skin substitutes (TESSs), and most of the studies or existing therapies use xenogeneic origin natural biomaterials or biosynthetic scaffolds. Objective To analyse clinical, histological integration and homeostasis parameters of a human TESS manufactured with fibrin-hyaluronic acid biomaterial (HA-Skin), grafted in immunodeficient mice for 8 weeks, and compared with the gold standard treatment (Autograft), a human TESS manufactured with fibrin-agarose biomaterial (AG-Skin) and secondary wound healing dressings. Methods Human TESSs and autografts were implanted into BALB/c mice after surgical excision. Secondary wound healing approach was achieved with biosynthetic collagen wound dressing (Biobrane â) and fibrin-hyaluronic acid or fibrin-agarose biomaterial without cells (Total N = 44). Clinical integration and homeostasis parameters were evaluated every two weeks for two months. Histological and immunohistochemical analyses were performed four and eight weeks after grafting. Results HA-Skin, AG-Skin and Autograft groups showed a proper clinical integration and epithelization eight weeks later. Scar evaluation revealed better results for Autograft and HA-Skin. Homeostasis analysis indicated similar values of transepidermal water loss and elasticity between HA-Skin (6.42 AE 0.75 g/h/m 2 , 0.42 AE 0.08 AU), Autograft (6.91 AE 1.28 g/h/m 2 , 0.40 AE 0.08 AU) and healthy mouse skin (6.40 AE 0.43 g/h/m 2 , 0.35 AE 0.03 AU). Histological results showed that human TESSs and autografts presented better skin structuration and higher expression of cytokeratins. Conclusions This study suggests that human TESS based on fibrin-hyaluronic acid biomaterial could be suitable for clinical application in the treatment of several dermatological pathologies (wound healing).
Mesenchymal stem cells or mesenchymal stromal cells (MSCs) are non-hematopoietic stromal cells that reside in many human organs and have been isolated from a variety of adult or fetal tissues such as adipose tissue, bone marrow and umbilical cord Wharton's jelly, among others. Because they are a heterogeneous population, International Society for Cellular Therapy has established 3 minimum criteria to characterize MSCs : i) adherence to plastic, ii) differentiation potential (osteogenic, chondrogenic and adipogenic lineages) and iii) expression of specific surface antigens (CD73+, CD90+, CD105+, CD34-, CD45-, CD11b-, CD14-, CD19-, CD79a-, HLA-DR-). Because of these characteristics, MSCs are useful for different applications and studies, most of them related with regenerative biomedicine. Epithelial differentiation of MSCs, for clinical use, is one of the main objectives in this field, due to, on the one hand, the difficulties to establish epithelial cell cultures and, on the other hand, the immunomodulatory capacity of MSCs that could increase the success of transplantation. According to this and the information compiled from bibliography, production of epithelial cells differentiated from MSCs is a complex procedure and a lot of techniques and culture media are necessary to explore. The objective of this review is to show the different methods of epithelial differentiation and remark the need to further study for being capable of establishing specific cell lines of epithelial cells differentiated from autogenic or allogenic MSCs.
Between 15% and 30% of HIV-infected subjects fail to increase their CD4 + T-cell counts despite continuous viral suppression (immunological nonresponders [INRs]). These subjects have a higher morbidity and mortality rate, but there are no effective treatments to reverse this situation so far. This study used data from an interrupted phase I/II clinical trial to evaluate safety and immune recovery after INRs were given four infusions, at baseline and at weeks 4, 8, and 20, with human allogeneic mesenchymal stromal cells from adipose tissue (Ad-MSCs). Based on the study design, the first 5 out of 15 INRs recruited received unblinded Ad-MSC infusions. They had a median CD4 + nadir count of 16/μL (range, 2-180) and CD4 + count of 253 cells per microliter (171-412) at baseline after 109 (54-237) months on antiretroviral treatment and 69 (52-91) months of continuous undetectable plasma HIV-RNA. After a year of follow-up, an independent committee recommended the suspension of the study because no increase of CD4 + T-cell counts or CD4 + /CD8 + ratios was observed. There were also no significant changes in the phenotype of different immunological lymphocyte subsets, percentages of natural killer cells, regulatory T cells, and dendritic cells, the inflammatory parameters analyzed, and cellular associated HIV-DNA in peripheral blood mononuclear cells. Furthermore, three subjects suffered venous thrombosis events directly related to the Ad-MSC infusions in the arms where the infusions were performed. Although the current study is based on a small sample of participants, the findings suggest that allogeneic Ad-MSC infusions are not effective to improve immune recovery in INR patients or to reduce immune activation or inflammation. ClinicalTrials.gov identifier: NCT0229004.
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