Minced Umbilical Cord Fragments as a Source of Cells for Orthopaedic Tissue Engineering: An In Vitro Study

A promising approach for musculoskeletal repair and regeneration is mesenchymal-stem-cell- (MSC-)based tissue engineering. The aim of the study was to apply a simple protocol based on mincing the umbilical cord (UC), without removing any blood vessels or using any enzymatic digestion, to rapidly obtain an adequate number of multipotent UC-MSCs. We obtained, at passage 1 (P1), a mean value of 4, 2 × 106 cells (SD 0,4) from each UC. At immunophenotypic characterization, cells were positive for CD73, CD90, CD105, CD44, CD29, and HLA-I and negative for CD34 and HLA-class II, with a subpopulation negative for both HLA-I and HLA-II. Newborn origin and multilineage potential toward bone, fat, cartilage, and muscle was demonstrated. Telomere length was similar to that of bone-marrow (BM) MSCs from young donors. The results suggest that simply collecting UC-MSCs at P1 from minced umbilical cord fragments allows to achieve a valuable population of cells suitable for orthopaedic tissue engineering

Insulin-like growth factor-I receptor activity is essential for Kaposi's sarcoma growth and survival

Kaposi's sarcoma (KS) is a highly vascular tumour and is the most common neoplasm associated with human immunodeficiency virus (HIV-1) infection. Growth factors, in particular vascular endothelial growth factor (VEGF), have been shown to play an important role in its development. The role of insulin-like growth factors (IGFs) in the pathophysiology of different tumours led us to evaluate the role of IGF system in KS. The IGF-I receptors (IGF-IR) were identified by immunohistochemistry in biopsies taken from patients with different AIDS/HIV-related KS stages and on KSIMM cells (an established KS-derived cell line). Insulin-like growth factor-I is a growth factor for KSIMM cells with a maximum increase of 3H-thymidine incorporation of 130±27.6% (P<0.05) similar to that induced by VEGF and with which it is additive (281±13%) (P<0.05). Moreover, specific blockade of the receptor (either by α IR3 antibody or by picropodophyllin, a recently described selective IGF-IR tyrosine phosphorylation inhibitor) induced KSIMM apoptosis, suggesting that IGF-IR agonists (IGF-I and -II) mediate antiapoptotic signals for these cells. We were able to identify an autocrine loop essential for KSIMM cell survival in which IGF-II is the IGF-IR agonist secreted by the cells. In conclusion, IGF-I pathway inhibition is a promising therapeutical approach for KS tumours

Wastewater-Based Epidemiology: Global Collaborative to Maximize Contributions in the Fight against COVID-19

Severe acute respiratory syndrome coronavirus 2 (SARSCoV-2), a novel member of the Coronaviridae family, has been identified as the etiologic agent of an ongoing pandemic of severe pneumonia known as COVID-19. To date there have been millions of cases of COVID-19 diagnosed in 184 countries with case fatality rates ranging from 1.8% in Germany to 12.5% in Italy. Limited diagnostic testing capacity and asymptomatic and oligosymptomatic infections result in significant uncertainty in the estimated extent of SARS-CoV-2 infection. Recent reports have documented that infection with SARS-CoV-2 is accompanied by persistent shedding of virus RNA in feces in 27% to 89% of patients at densities from 0.8 to 7.5 log10 gene copies per gram. The presence of SARS-CoV-2 RNA in feces raises the potential to survey sewage for virus RNA to inform epidemiological monitoring of COVID-19, which we refer to as wastewater-based epidemiology (WBE), but is also known as environmental surveillance

Myeloablative doses of yttrium-90-ibritumomab tiuxetan and the risk of secondary myelodysplasia/acute myelogenous leukemia

BACKGROUND: Because the long-term toxicity of myeloablative radioimmunotherapy remains a matter of concern, the authors evaluated the hematopoietic damage and incidence of secondary myelodysplastic syndrome and acute myelogenous leukemia (sMDS/AML) in patients who received myeloablative doses of the radiolabeled antibody yttrium-90 ( 90Y)-ibritumomab tiuxetan. METHODS: The occurrence of sMDS/AML was investigated prospectively in 53 elderly patients with non-Hodgkin lymphoma (NHL) who underwent an autograft after high-dose radioimmunotherapy (HD-RIT) myeloablative conditioning with 90Y-ibritumomab tiuxetan. Bone marrow (BM) hematopoietic progenitors and telomere length (TL) also were investigated. RESULTS: At a median follow-up of 49 months, 4 patients developed sMDS/AML at 6 months, 12 months, 27 months, and 36 months after HD-RIT, and the 5-year cumulative incidence of sMDS/AML was 8.29%. A significant but transient decrease in BM granulocyte-macrophage progenitors was observed; whereas multilineage, erythroid, and fibroblast progenitors were unaffected. A significant and persistent shortening of BM TL also was detected. A matched-pair analysis comparing the study patients with 55 NHL patients who underwent autografts after chemotherapy-based myeloablative conditioning demonstrated a 8.05% 5-year cumulative incidence of sMDS/AML. CONCLUSIONS: HD-RIT for patients with NHL was associated with 1) limited toxicity on hematopoietic progenitors, 2) accelerated TL shortening, and 3) non-negligible incidence of sMDS/AML, which nevertheless was comparable to the incidence observed in a matched group of patients who received chemotherapy-based conditioning. Thus, in the current series of elderly patients with NHL, the development of sMDS/AML was not influenced substantially by HD-RIT

A screening platform for glioma growth and invasion using bioluminescence imaging: Laboratory investigation

10.3171/2008.8.JNS08644Journal of Neurosurgery1112238-246JONS

Capillary-induced contact guidance

Topographical features are known to impose capillary forces on liquid droplets, and this phenomenon is exploited in applications such as printing, coatings, textiles and microfluidics. Surface topographies also influence the behavior of biological cells (i.e., contact guidance), with implications ranging from medicine to agriculture. An accurate physical description of how cells detect and respond to surface topographies is necessary in order to move beyond a purely heuristic approach to optimizing the topographies of biomaterial interfaces. Here, we have used a combination of Langmuir−Blodgett lithography and nanoimprinting to generate a range of synthetic microstructured surfaces with grooves of subcellular dimensions in order to investigate the influence of capillary forces on the biological process of contact guidance. The physical−chemical properties of these surfaces were assessed by measuring the anisotropic spreading of sessile water droplets. Having established the physical properties of each surface, we then investigated the influence of capillary forces on the processes of cellular contact guidance in biological organisms, using mammalian osteoblasts and germinating fungal spores as tester organisms. Our results demonstrate that capillary effects are present in topographical contact guidance and should therefore be considered in any physical model that seeks to predict how cells will respond to a particular surface topography