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1.
Nature ; 626(7998): 367-376, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38092041

ABSTRACT

Implantation of the human embryo begins a critical developmental stage that comprises profound events including axis formation, gastrulation and the emergence of haematopoietic system1,2. Our mechanistic knowledge of this window of human life remains limited due to restricted access to in vivo samples for both technical and ethical reasons3-5. Stem cell models of human embryo have emerged to help unlock the mysteries of this stage6-16. Here we present a genetically inducible stem cell-derived embryoid model of early post-implantation human embryogenesis that captures the reciprocal codevelopment of embryonic tissue and the extra-embryonic endoderm and mesoderm niche with early haematopoiesis. This model is produced from induced pluripotent stem cells and shows unanticipated self-organizing cellular programmes similar to those that occur in embryogenesis, including the formation of amniotic cavity and bilaminar disc morphologies as well as the generation of an anterior hypoblast pole and posterior domain. The extra-embryonic layer in these embryoids lacks trophoblast and shows advanced multilineage yolk sac tissue-like morphogenesis that harbours a process similar to distinct waves of haematopoiesis, including the emergence of erythroid-, megakaryocyte-, myeloid- and lymphoid-like cells. This model presents an easy-to-use, high-throughput, reproducible and scalable platform to probe multifaceted aspects of human development and blood formation at the early post-implantation stage. It will provide a tractable human-based model for drug testing and disease modelling.


Subject(s)
Embryonic Development , Germ Layers , Hematopoiesis , Yolk Sac , Humans , Embryo Implantation , Endoderm/cytology , Endoderm/embryology , Germ Layers/cytology , Germ Layers/embryology , Yolk Sac/cytology , Yolk Sac/embryology , Mesoderm/cytology , Mesoderm/embryology , Induced Pluripotent Stem Cells/cytology , Amnion/cytology , Amnion/embryology , Embryoid Bodies/cytology , Cell Lineage , Developmental Biology/methods , Developmental Biology/trends
2.
Iran J Pharm Res ; 19(2): 61-69, 2020.
Article in English | MEDLINE | ID: mdl-33224211

ABSTRACT

Cancer is now a global concern, and control of the function of cancer cells is recognized as an important challenge. Although many aggressive chemical and radiation methods are in practice to eliminate cancer cells, most of them imply severe adverse toxic effects on patients. Taking advantage of natural physical differences between cancer and normal cells might benefit the patient with more specific cytotoxicity and fewer adverse effects. Physical factors are the main means that can influence cell-biomaterial interaction. To explore the importance of attachment phenomena on cancer cells in this research, polydimethylsiloxane (PDMS) substrates with varied stiffness and roughness were synthesized and lung cancer cell's behavior on these surfaces was examined. To achieve diverse surface topography SDBD plasma was used at various exposure times, and different stiffness was obtained by changing in curing agent amount. Atomic force microscopy (AFM) and tensile modulus were employed to the characterization of roughness and stiffness respectively. Lung cancer cell survival and growth were studied by MTT and image processing analysis. The results indicated that softer and rougher surface made lung cancer cells to die. The number of detached cells, mean space of the detached cells, cellular coverage of surface, and the ratio of detached/ all cellular coverage were significantly affected by roughness and stiffness. Therefore, physical factors can control cell function, especially in lung cancer cells and these results might provide a strong base to help cancer cell removal.

3.
Analyst ; 144(19): 5810-5828, 2019 Sep 23.
Article in English | MEDLINE | ID: mdl-31469152

ABSTRACT

Fourier transform infrared (FTIR) spectroscopy is a well-known method of analysis, with various applications, including promising potential for analyzing biological samples. In the bio-spectroscopy of cells, Mie scattering may increase, which then causes spectral distortion, due to the similarity of cell size with the IR medium-wavelength. These changes make the spectrum unreliable. In previous scattering elimination studies, questionable estimations were considered. For instance, all cells were considered as spherical objects or cell size was estimated randomly. In an attempt to provide the best equation based on the natural existence of cells for the FTIR Mie scattering correction, we examined the actual biological data of cells - as opposed to those yielded from mathematical manipulations. So five biological factors: cell size, shape, granularity, circularity, and edge irregularities, for each cell line were considered as factors which cause scattering. For measuring cell size, roundness and edge irregularity, microscopy images were obtained and processed. For evaluating cell line granularity, flow cytometry was used. Finally, by including these factors, an algorithm was designed. To assess the accuracy of the proposed algorithm, the trypsinized cell spectrum was considered as the high scattering spectrum. Cells were also cultured on a MirrIR slide, and their ATR-FTIR spectrum was considered as the minimum scattering spectrum. The algorithm using the abovementioned five characteristics was used for 13 different cell lines, and in some cases the corrected spectrum demonstrated more than 97% resemblance with the ATR spectra of the same cells. A comparison between the results of this algorithm with the Bassan et al. (2017) algorithm for scattering correction that is freely available on the Internet was then conducted on two different cell lines, clearly showing the advantages of our algorithm, in terms of accuracy and precision. Therefore, this method can be viewed as a more suitable solution for scattering correction in cell investigations.


Subject(s)
Cell Line, Tumor , Spectroscopy, Fourier Transform Infrared/methods , Algorithms , Cell Line, Tumor/chemistry , Cell Line, Tumor/cytology , Humans , Infrared Rays , Scattering, Radiation
4.
Life Sci ; 233: 116754, 2019 Sep 15.
Article in English | MEDLINE | ID: mdl-31415768

ABSTRACT

Peptides are oligomers of amino acids, which have been used in a wide range of applications, particularly in medical and pharmaceutical sciences. Linear peptides have been extensively developed in various fields of medicine as therapeutics or targeting agents. The branched structure of peptide dendrimers with peptide (commonly, poly l­Lysine) or non-peptide (commonly poly­amidoamine) core, often exhibits valuable novel features, improves stability and enhances the functionality of peptide in comparison with small linear peptides. The potential applications of Branched and hyper-branched peptidic structures which are known as peptide dendrimers in biomedical sciences have been approved vastly. A peptide dendrimer contains three distinct parts including core, building blocks and branching units or surface functional groups. These structures provide a lot of opportunities in the pharmaceutical field, particularly for novel drug development. In this review, a brief summary of different biomedical applications of peptide dendrimers is presented, and peptide dendrimers as active pharmaceutical ingredients and drug delivery carriers are discussed. Applications of peptide dendrimers in vaccines and diagnostic tools are also presented, in brief. Generally, peptide dendrimers are promising biomaterials with high evolution rate for clinical and non-clinical applications in medicine.


Subject(s)
Biocompatible Materials/chemistry , Biotechnology , Dendrimers/chemistry , Drug Carriers/chemistry , Drug Delivery Systems , Peptide Fragments/chemistry , Humans
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