scholarly journals Interleukin 4 Moderately Affects Competence of Pluripotent Stem Cells for Myogenic Conversion

2019 ◽  
Vol 20 (16) ◽  
pp. 3932 ◽  
Author(s):  
Barbara Świerczek-Lasek ◽  
Jacek Neska ◽  
Agata Kominek ◽  
Łukasz Tolak ◽  
Tomasz Czajkowski ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Pluripotent Stem Cells ◽  
Muscle Development ◽  
Embryonic Stem ◽  
Interleukin 4 ◽  
Myogenic Cells ◽  
The Impact

Pluripotent stem cells convert into skeletal muscle tissue during teratoma formation or chimeric animal development. Thus, they are characterized by naive myogenic potential. Numerous attempts have been made to develop protocols enabling efficient and safe conversion of pluripotent stem cells into functional myogenic cells in vitro. Despite significant progress in the field, generation of myogenic cells from pluripotent stem cells is still challenging—i.e., currently available methods require genetic modifications, animal-derived reagents, or are long lasting—and, therefore, should be further improved. In the current study, we investigated the influence of interleukin 4, a factor regulating inter alia migration and fusion of myogenic cells and necessary for proper skeletal muscle development and maintenance, on pluripotent stem cells. We assessed the impact of interleukin 4 on proliferation, selected gene expression, and ability to fuse in case of both undifferentiated and differentiating mouse embryonic stem cells. Our results revealed that interleukin 4 slightly improves fusion of pluripotent stem cells with myoblasts leading to the formation of hybrid myotubes. Moreover, it increases the level of early myogenic genes such as Mesogenin1, Pax3, and Pax7 in differentiating embryonic stem cells. Thus, interleukin 4 moderately enhances competence of mouse pluripotent stem cells for myogenic conversion.

Cyclosporin A promotes invasion and migration of extravillous trophoblast cells derived from human induced pluripotent stem cells and human embryonic stem cells

2020 ◽  
Author(s):  
Jiaxing Wang ◽  
Ping Long ◽  
Shengnan Tian ◽  
Weihua Zu ◽  
Jing Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Pluripotent Stem Cells ◽  
Embryonic Stem ◽  
Extravillous Trophoblast ◽  
Invasion And Migration ◽  
And Migration ◽  
Induced Pluripotent

Abstract Background Extravillous trophoblast (EVT) cells play an essential role in the maternal-fetal interaction. Although abnormal development and function of EVT cells, including impaired migration and invasion capability, are believed to be etiologically linked to severe pregnancy disorders including pre-eclampsia (PE), the associated molecular mechanisms are not clear ascribed to the lack of an appropriate cell model in vitro. Cyclosporine A (CsA) is a macrolide immunosuppressant and is also used in clinic to improve pregnancy outcomes. However, whether CsA has any effects on the function of EVT cells has not been well investigated. Methods In this study, we induced differentiation of human induced pluripotent stem cells (hiPSCs) and human embryonic stem cells (hESCs) into EVT cells (hiPSC-EVT and hESC-EVT cells, respectively) by Y27632, NRG1, A83-01 and matrigel, and collected these derived EVT cells by flow cytometry for sorting cells positive for double HLA-G and KRT7, which are EVT markers. We then investigated the effects of CsA on the invasion and migration of these derived EVT cells. Results We found that the hiPSC-EVT and hESC-EVT cells expressed high levels of the EVT markers such as KRT7, ITGA5 and HLA-G but low levels of OCT4, a stem cell marker, and that CsA significantly promoted the invasion and migration of hiPSC-EVT and hESC-EVT cells. Conclusions We successfully generated hiPSC/hESC-derived human EVT cells, which may be applicable for investigating the remodeling process of spiral arteries remodeling and the possible mechanisms of EVT-related diseases in vitro. Furthermore, our findings provide direct evidence that CsA regulates the function of EVT cells and molecular basis by which CsA may be used to treat pregnancy complications in clinic associated with deficient EVT function.

scholarly journals Human Cell Modeling for Cardiovascular Diseases

2020 ◽  
Vol 21 (17) ◽  
pp. 6388
Author(s):  
Melania Lippi ◽  
Ilaria Stadiotti ◽  
Giulio Pompilio ◽  
Elena Sommariva
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Cardiovascular Diseases ◽  
Human Cell ◽  
Pluripotent Stem Cells ◽  
Disease Modeling ◽  
Embryonic Stem ◽  
Cell Models ◽  
Advantages And Disadvantages

The availability of appropriate and reliable in vitro cell models recapitulating human cardiovascular diseases has been the aim of numerous researchers, in order to retrace pathologic phenotypes, elucidate molecular mechanisms, and discover therapies using simple and reproducible techniques. In the past years, several human cell types have been utilized for these goals, including heterologous systems, cardiovascular and non-cardiovascular primary cells, and embryonic stem cells. The introduction of induced pluripotent stem cells and their differentiation potential brought new prospects for large-scale cardiovascular experiments, bypassing ethical concerns of embryonic stem cells and providing an advanced tool for disease modeling, diagnosis, and therapy. Each model has its advantages and disadvantages in terms of accessibility, maintenance, throughput, physiological relevance, recapitulation of the disease. A higher level of complexity in diseases modeling has been achieved with multicellular co-cultures. Furthermore, the important progresses reached by bioengineering during the last years, together with the opportunities given by pluripotent stem cells, have allowed the generation of increasingly advanced in vitro three-dimensional tissue-like constructs mimicking in vivo physiology. This review provides an overview of the main cell models used in cardiovascular research, highlighting the pros and cons of each, and describing examples of practical applications in disease modeling.

scholarly journals Defining totipotency using criteria of increasing stringency

2020 ◽  
Author(s):  
Eszter Posfai ◽  
John Paul Schell ◽  
Adrian Janiszewski ◽  
Isidora Rovic ◽  
Alexander Murray ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Single Cell ◽  
Pluripotent Stem Cells ◽  
Embryonic Stem ◽  
Cell Types ◽  
Differentiated Cells ◽  
Totipotent Cell

AbstractTotipotency is the ability of a single cell to give rise to all the differentiated cells that build the conceptus, yet how to capture this property in vitro remains incompletely understood. Defining totipotency relies upon a variety of assays of variable stringency. Here we describe criteria to define totipotency. We illustrate how distinct criteria of increasing stringency can be used to judge totipotency by evaluating candidate totipotent cell types in the mouse, including early blastomeres and expanded or extended pluripotent stem cells. Our data challenge the notion that expanded or extended pluripotent states harbor increased totipotent potential relative to conventional embryonic stem cells under in vivo conditions.

scholarly journals Komórki macierzyste i reprogramowanie komórek somatycznych – wybrane zagadnienia

2018 ◽  
Vol 15 (1) ◽  
pp. 35-42
Author(s):  
Joanna P. Wróblewska
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Embryonic Stem ◽  
Induced Pluripotent

Historia badań nad komórkami macierzystymi (embryonic stem cells, ES) sięga początków XX wieku. Już wtedy obserwowano komórki, które w organizmie myszy tworzyły specyficzny, wysoce zróżnicowany guz nowotworowy - potworniak. Jednakże dopiero druga połowa XX wieku przyniosła znaczący postęp w badaniach, co zaowocowało uzyskaniem pierwszych linii komórek macierzystych w hodowli in vitro. Poznanie cech charakterystycznych i potencjału komórek ES wzbudziło ogromne nadzieje na wykorzystanie komórek macierzystych nie tylko w badaniach podstawowych, ale przede wszystkim w nowo rozwijającej się gałęzi medycyny – medycynie regeneracyjnej. Jednakże ze względu na etyczne kwestie związane ze sposobem pozyskiwania komórek ES, badania tego typu nie miały większych szans na powodzenie. Przełom nastąpił w 2006 roku, po opracowaniu metody uzyskiwania indukowalnych komórek pluripotentnych (induced pluripotent stem cells, iPSC) na drodze reprogramowania komórek somatycznych. Komórki iPS posiadają wszystkie zalety komórek ES, jednakże ich pozyskiwanie nie jest obarczone restrykcjami prawnymi i etycznym. Daje to nadzieję na szybki postęp badań z zakresu medycyny regeneracyjnej i terapii komórkowej, zwłaszcza w przypadku chorób dotychczas uznawanych za nieuleczalne.

A Population of Small CXCR4+ SSEA-1+ Oct-4+ Embryonic-Like Stem Cells Identified in Adult Bone Marrow.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3623-3623
Author(s):  
Magda Kucia ◽  
Ryan Reca ◽  
Janina Ratajczak ◽  
Mariusz Z. Ratajczak
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Embryonic Stem Cells ◽  
Pluripotent Stem Cells ◽  
Embryonic Stem ◽  
Hematopoietic Tissue ◽  
Isolation And Identification ◽  
Hematopoietic Stem ◽  
Stem Cell Populations

Abstract We demonstrated that bone marrow (BM) stem cells are heterogenous and in addition to hematopoietic stem cells (HSC) BM also contains non-hematopoietic tissue committed stem cells (TCSC) for skeletal muscle, heart, neural tissue, epidermis and liver (Leukemia2004:18;29–40). In our follow up studies by employing multiparameter sorting we identified in murine BM a homogenous population of rare (~0.02% of BMMNC) Sca-1+ lin− CD45− cells that express by RQ-PCR and immunhistochemistry markers of pluripotent stem cells (PSC) such as SSEA-1, Oct-4, Nanog and Rex-1 and highly express Rif-1 telomerase protein. More important the direct electronmicroscopical analysis revealed that these cells display several features typical for primary embryonic stem cells such as i) small size (~3 μm in diameter), ii) poses large nuclei surrounded by a narrow rim of cytoplasm, and iii) contain open-type chromatin (euchromatin) that is typical for embryonic stem cells. Their number is highest in BM from young (1–2 month-old) mice and decreases with age. It is also significantly diminished in short living DBA/2J mice as compared to long living B6 mice. These cells in vitro respond strongly to several motomorphogens such as SDF-1, HGF and LIF and co-express the corresponding receptors such as CXCR4, c-met and LIF-R respectively on their surface. Interestingly, they adhere to fibronectin, and undergo emperipolesis in fibroblasts, thus they may be co-isolated with BM adherent cells. Furthermore, they are mobilized into peripheral blood during tissue/organ injuries (e.g., heart infarct, stroke). In in vitro cultures they differentiate into cells from different germ-layers (e.g., form neurospheres, grow cardiomyocytes). Thus, these findings support the theory of BM containing a reserve population of embryonic-like/pluripotent stem cells and it is also possible that several of the recently described BM-derived CD45− stem cell populations (e.g., MAPC, USSC or MIAMI cells) could in fact overlap with these rare non-hematopoietic CD45− stem cells identified by us, but due to the differences in the experimental approaches employed for their isolation and identification, were assigned different names. We postulate that this population of CD45− embryonic-like cells expressing pluripotent and tissue committed markers identified by us is an ideal source of cells for regeneration.

scholarly journals Testicular somatic cell-like cells derived from embryonic stem cells induce differentiation of epiblasts into germ cells

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Holly Rore ◽  
Nicholas Owen ◽  
Raul Eduardo Piña-Aguilar ◽  
Kevin Docherty ◽  
Ryohei Sekido
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Somatic Cell ◽  
Germ Cells ◽  
Pluripotent Stem Cells ◽  
Seminiferous Tubule ◽  
Embryonic Stem ◽  
In Vitro Reconstitution ◽  
Real Challenge

AbstractRegeneration of the testis from pluripotent stem cells is a real challenge, reflecting the complexity of the interaction of germ cells and somatic cells. Here we report the generation of testicular somatic cell-like cells (TesLCs) including Sertoli cell-like cells (SCLCs) from mouse embryonic stem cells (ESCs) in xeno-free culture. We find that Nr5a1/SF1 is critical for interaction between SCLCs and PGCLCs. Intriguingly, co-culture of TesLCs with epiblast-like cells (EpiLCs), rather than PGCLCs, results in self-organised aggregates, or testicular organoids. In the organoid, EpiLCs differentiate into PGCLCs or gonocyte-like cells that are enclosed within a seminiferous tubule-like structure composed of SCLCs. Furthermore, conditioned medium prepared from TesLCs has a robust inducible activity to differentiate EpiLCs into PGCLCs. Our results demonstrate conditions for in vitro reconstitution of a testicular environment from ESCs and provide further insights into the generation of sperm entirely in xeno-free culture.

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