To our knowledge, this is the first report of a clinical trial of cell therapy using autologous stem cells obtained from a lipoaspirate. Our results indicate that our protocol is feasible and safe for the treatment of fistulas in Crohn's disease. The number of patients included and the uncontrolled nature of Phase I clinical trials do not allow demonstration of the effectiveness of the treatment. However, the results of the present study encourage to perform further studies in Phase II.
Background: Identification of effective treatments in severe cases of COVID-19 requiring mechanical ventilation represents an unmet medical need. Our aim was to determine whether the administration of adiposetissue derived mesenchymal stromal cells (AT-MSC) is safe and potentially useful in these patients. Methods: Thirteen COVID-19 adult patients under invasive mechanical ventilation who had received previous antiviral and/or anti-inflammatory treatments (including steroids, lopinavir/ritonavir, hydroxychloroquine and/or tocilizumab, among others) were treated with allogeneic AT-MSC. Ten patients received two doses, with the second dose administered a median of 3 days (interquartile range-IQR-1 day) after the first one. Two patients received a single dose and another patient received 3 doses. Median number of cells per dose was 0.98 £ 10 6 (IQR 0.50 £ 10 6 ) AT-MSC/kg of recipient's body weight. Potential adverse effects related to cell infusion and clinical outcome were assessed. Additional parameters analyzed included changes in imaging, analytical and inflammatory parameters.
The clinical management of cancer has evolved in recent years towards more personalized strategies that require a comprehensive knowledge of the complex molecular features involved in tumor growth and evolution, and the development of drug resistance mechanisms leading to disease progression. Droplet digital PCR (ddPCR) has become one of the most accurate and reliable tools for the examination of genetic alterations in a wide variety of cancers because of its high sensitivity and specificity. ddPCR is currently being applied for absolute allele quantification, rare mutation detection, analysis of copy number variations, DNA methylation, and gene rearrangements in different kinds of clinical samples. This methodology has proven useful for the evaluation of archival tumor tissues, where poor DNA quality and limited sample availability are major obstacles for standard methods, providing less subjective and more automated quantitative results. However, most applications of ddPCR in cancer are focused on liquid biopsies (including cell-free DNA as well as circulating tumor cells) because these represent non-invasive alternatives to tissue biopsies that can more accurately reflect intratumoral heterogeneity and track the dynamic changes in tumor burden that occur in response to treatment at different times during follow-up. A broad spectrum of molecular markers have been interrogated in blood using ddPCR for diagnostic, predictive, and monitoring purposes in various malignancies. Emerging alternative approaches using other body fluids such as cerebrospinal fluid and urine are also currently being developed. This article aims to give a complete overview of ddPCR applications for molecular screening in oncology.
Cultivated murine bone marrow mesenchymal stem cells (MSCs) frequently accumulate chromosome abnormalities, become oncogenically transformed, and generate sarcomas when transplanted in mice. Although human MSCs appear to be more resistant, oncogenic transformation has also been observed in MSCs cultivated past the senescence phase. Cell therapy for tissue regeneration using human autologous MSCs requires transplantation of cells previously expanded in vitro. Thus, an important concern is to determine if oncogenic transformation is a necessary outcome of the expansion procedures. We have analyzed the proliferation capacity, organ colonization, and oncogenicity of enhanced green fluorescent protein and luciferase-labeled human adipose tissue-derived mesenchymal stem cells (hAMSCs), implanted in immunocompromised mice during a prolonged time period (8 months) using a non-invasive bioluminescence imaging procedure. Our data indicates that the liver was the preferred target organ for colonization by intramuscular or intravenous implantation of hAMSCs. The implanted cells tended to maintain a steady state, population did not proliferate rapidly after implantation, and no detectable chromosomal abnormalities nor tumors formed during the 8 months of residence in the host's tissues. It would appear that hAMSCs, contrary to their murine correlatives, could be safe candidates for autologous cell therapy procedures since in our experiments they show undetectable predisposition to oncogenic transformation after cultivation in vitro and implantation in mice.
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