Establishment and Characterization of NCC-DDLPS4-C1: A Novel Patient-Derived Cell Line of Dedifferentiated Liposarcoma

Dedifferentiated liposarcoma (DDLPS) is a highly malignant sarcoma characterized by the co-amplification of MDM2 and CDK4. Although systemic chemotherapy is recommended for unresectable or metastatic cases, DDLPS is insensitive to conventional chemotherapy, leading to an unfavorable prognosis. Therefore, novel treatment methods are urgently required. Patient-derived cell lines are essential in preclinical studies. Recently, large-scale screening studies using a number of cell lines have been actively conducted for the development of new therapeutic drugs. However, the DDLPS cell line cannot be obtained from public cell banks owing to its rarity, hindering screening studies. As such, novel DDLPS cell lines need to be established. Accordingly, this study aimed to establish a novel DDLPS cell line from surgical specimens. The cell line was named NCC-DDLPS4-C1. NCC-DDLPS4-C1 cells retained copy number alterations corresponding to the original tumors. Further, the cells demonstrated constant growth, spheroid formation, and equivalent invasiveness to MG63 osteosarcoma cells. We also conducted drug screening and integrated the results with those of the previously reported DDLPS cell lines. Consequently, we identified the histone deacetylase inhibitor romidepsin as a novel candidate drug. In conclusion, the NCC-DDLPS4-C1 cell line is a useful tool for the basic study of DDLPS.

Methodological aspects of the development of product files for biomedical cell products

Preparation of a product file (PF) for a biomedical cell product (BCP) is an important stage in the preparation of documents for marketing authorisation. The PF is the main document of a regulatory submission and is used as the basis for BCP quality control. The requirements for the content of a PF, including appropriate specifications, are laid out in the relevant laws and regulations that support Federal Law No. 180-FZ “On Biomedical Cell Products” of 23.06.2016. However, given the novelty of the Russian legislative framework for innovative products for human use represented by BCPs, the specificity of their composition (i.e., components based on viable human cells) which differs significantly from conventional medicines, and lack of marketing authorisation experience— there is a need to examine specific aspects of a BCP PF. The aim of the study was to formulate methodological approaches to the development and preparation of a BCP PF in accordance with the national legislation and taking into account the experience of foreign regulatory authorities in evaluation of regulatory submissions for BCP analogues. The paper summarises the national regulatory requirements for the description of quality characteristics of cell lines used as components in BCPs, as well as test methods and test procedures used for cell line quality control. These data are required both for quality control of BCP samples, and for preparation of the Expert Commission Conclusion. The paper looks into the content of cellular and process-related impurities in a cell line and a finished BCP, and presents considerations on the description of the viral safety strategy for the finished product and for the cells from the master and working cell banks. The approaches to the presentation of quality characteristics and quality control methods for a finished BCP and for the cell line used in its production could be used by BCP developers for preparation of a PF.

Assisted Reproductive Technology in Neotropical Deer: A Model Approach to Preserving Genetic Diversity

One of the most significant challenges in deer is the ability to maintain genetic diversity, avoiding inbreeding and sustaining population health and reproduction. Although our general knowledge of reproductive physiology is improving, it appears that the application of assisted reproductive technology (ART) will more efficiently advance wildlife conservation efforts and preserve genetic diversity. The purpose of this review is to present the most important results obtained with the use of ART in Neotropical deer. Thus, the state-of-the-art for estrus synchronization, semen technology, artificial insemination, and in vivo embryo production will be presented. In vitro embryo production (IVP) is also a biotechnology that is taking initial steps in deer. In this aspect, the approach with the proteomics of ovarian follicular fluid is being used as a tool for a better understanding of oocyte maturation. Finally, cell banks and the use of interspecific somatic cell nuclear transfer (iSCNT) as well as the use of stem cells for gametes differentiation are promising techniques.

Toward the Operability of Flotation Systems under Uncertainty

The purpose of this work was to analyze the requirements for the operational feasibility of flotation systems as well as the effects of the selection of flotation equipment and metal price uncertainty. A procedure based on mathematical optimization and uncertainty analysis was implemented to achieve this aim. The optimization included flotation and grinding stages operating under uncertainty, whereas the uncertainty analysis considered the Monte Carlo method. The results obtained indicate a small number of optimal flotation structures from the economic point of view. Considering the relationship between the economic performance and metallurgical parameters, we established that these structures exhibited favorable conditions for operating under uncertainty. Such conditions were proportional to the percentages representing each structure in the optimal set; i.e., a higher percentage of a structure implied a greater capacity to face operational and metal price changes. The set of optimal structures included configurations implementing cell banks, flotation columns, or both, indicating the influence of the flotation equipment type on the optimal structures. We also established the influence of metal price on the number of optimal structures. Therefore, the results obtained allowed us to separate the design of the flotation systems into two stages: first, a set of optimal structures exhibiting favorable conditions for facing uncertainty is determined; second, the optimal operation is established via resilience/flexibility approaches after the previous determination of the equipment design parameters.

Principles for establishment of the stem cell bank and its applications on management of sports injuries

Background The stem cells of the stem cell banks have prominent problems for insufficient sources, easy contamination, unstable biological characteristics after serial subcultivations, and high cost. Methods After collecting the construction processes of the existing stem cell banks and suggestions from authoritative experts in the past 10 years, 230 reference principles were obtained, and finally, the principles of “5C” for the establishment of modern standardized stem cell banks were summarized, and their related applications on the management of sports injuries were reviewed as well. Results The basic principles of “5C” for the establishment of modern standardized stem cell banks include (1) principle of informed consent, (2) confidentiality principle, (3) conformity principle, (4) contamination-free principle, and (5) commonweal principle. The applications of stem cells on repairs, reconstructions, and regenerations of sports injuries were also reviewed, especially in tissue-engineered cartilage, tissue-engineered meniscus, and tissue-engineered ligament. Conclusions The proposal of the basic principles of “5C” is conducive to relevant stem cell researchers and clinical medical experts to build modern stem cell banks in a more standardized and efficient manner while avoiding some major mistakes or problems that may occur in the future. On this basis, stem cells from stem cell banks would be increasingly used in the management of sports injuries. More importantly, these days, getting stem cell samples are difficult in a short time, and such banks with proper legal consent may help the scientific community.