scholarly journals Sculpting with stem cells: how models of embryo development take shape

Development ◽  
2021 ◽  
Vol 148 (24) ◽  
Author(s):  
Jesse V. Veenvliet ◽  
Pierre-François Lenne ◽  
David A. Turner ◽  
Iftach Nachman ◽  
Vikas Trivedi
Keyword(s):  
Stem Cells ◽  
Boundary Conditions ◽  
Pluripotent Stem Cells ◽  
Phenotypic Variability ◽  
Feedback Loops ◽  
Mammalian Embryo ◽  
Spatial And Temporal Scales ◽  
Cellular Environment ◽  
Developmental Engineering

ABSTRACT During embryogenesis, organisms acquire their shape given boundary conditions that impose geometrical, mechanical and biochemical constraints. A detailed integrative understanding how these morphogenetic information modules pattern and shape the mammalian embryo is still lacking, mostly owing to the inaccessibility of the embryo in vivo for direct observation and manipulation. These impediments are circumvented by the developmental engineering of embryo-like structures (stembryos) from pluripotent stem cells that are easy to access, track, manipulate and scale. Here, we explain how unlocking distinct levels of embryo-like architecture through controlled modulations of the cellular environment enables the identification of minimal sets of mechanical and biochemical inputs necessary to pattern and shape the mammalian embryo. We detail how this can be complemented with precise measurements and manipulations of tissue biochemistry, mechanics and geometry across spatial and temporal scales to provide insights into the mechanochemical feedback loops governing embryo morphogenesis. Finally, we discuss how, even in the absence of active manipulations, stembryos display intrinsic phenotypic variability that can be leveraged to define the constraints that ensure reproducible morphogenesis in vivo.

scholarly journals Induced Pluripotent Stem Cells (iPSCs) in Vascular Research: from Two- to Three-Dimensional Organoids

2021 ◽  
Author(s):  
Anja Trillhaase ◽  
Marlon Maertens ◽  
Zouhair Aherrahrou ◽  
Jeanette Erdmann
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Induced Pluripotent Stem Cells ◽  
Stem Cell Research ◽  
Pluripotent Stem Cells ◽  
Embryonic Stem ◽  
Cell Types ◽  
3D Models ◽  
Induced Pluripotent

AbstractStem cell technology has been around for almost 30 years and in that time has grown into an enormous field. The stem cell technique progressed from the first successful isolation of mammalian embryonic stem cells (ESCs) in the 1990s, to the production of human induced-pluripotent stem cells (iPSCs) in the early 2000s, to finally culminate in the differentiation of pluripotent cells into highly specialized cell types, such as neurons, endothelial cells (ECs), cardiomyocytes, fibroblasts, and lung and intestinal cells, in the last decades. In recent times, we have attained a new height in stem cell research whereby we can produce 3D organoids derived from stem cells that more accurately mimic the in vivo environment. This review summarizes the development of stem cell research in the context of vascular research ranging from differentiation techniques of ECs and smooth muscle cells (SMCs) to the generation of vascularized 3D organoids. Furthermore, the different techniques are critically reviewed, and future applications of current 3D models are reported. Graphical abstract

Abstract 18663: Myocardial Heterogeneity in Heart With Postinfarction LV Remodeling and its Response to Cell Therapy

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
weina cui ◽  
lei ye ◽  
albert jang ◽  
qiang xiong ◽  
pengyuan zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Treated Group ◽  
Border Zone ◽  
Flux Rate ◽  
Lv Remodeling ◽  
Myocardial Heterogeneity ◽  
Induced Pluripotent ◽  
Myocardial Bioenergetics

Rationale and Objective: Human induced pluripotent stem cells (hiPSCs) hold promise for myocardial repair following injury. Here, we investigated the functional impact and myocardial heterogeneity of bioenergetics using a porcine model of post infarction LV remodeling, and 2 dimensional chemical shift imaging (2D CSI) P-31 MR spectroscopy. Methods and Results: Ischemia-reperfusion (I/R) injury was surgically induced by occlusion distal LAD (OCCL) for 60 minutes in female Yorkshire farm swine (≈15kg), then randomly assigned to experimental groups: 1) 16 million human induced pluripotent stem cells (hiPSC) derived cardio myocytes (CMs), smooth muscle cells (SMC) and Endothelia cells (ECs) were directly myocardial injected through an epicardial fibrin patch (P+Cell, n= 4), 2) open patch (fibrin patch with no cell) were placed over the injury site (P w/o Cell, n=4). Size matched normal (n=9) and OCCL only (n=5) pigs were also studied. Four weeks after I/R, 2D CSI MRS studies were performed in a 9.4T/ 65 cm bore magnet. In vivo myocardial energetic mapping was achieved using 31 P 2D CSI. To measure the forward flux rate PCr to ATP, 2D CSI data were acquired with or without saturation on ATPγ resonance. I/R injury has a heterogeneous effect on LV myocardial bioenergetics. Myocardial creatine phosphate (PCr)/ATP ratio is significantly decreased in border zone (BZ) of the infarction than the myocardial areas remote from the scar (RZ) in cell treated and patch only groups (1.54+/- 0.05 vs 2.25 +/- 0.10, 1.49+/-0.07 vs 2.34 +/- 0.07, BZ vs RZ, p<0.05). The BZ PCr/ATP ratio is improved in the cell treated group compared with open patch group (1.71 +/- 0.05 vs. 1.54 +/- 0.05, p<0.05). The forward flux rate constant of PCr/ATP (k pcr→ATP ) in the border zone is slightly increased in cell treated group compared with patch only group (0.29 +/- 0.02 vs 0.22 +/- 0.04 , p<0.05) Conclusion: The approach of 2D CSI 31 P MRS can effectively map the heterogeneity of myocardial ATP flux rate via CK In Vivo porcine hearts. Postinfarction LV remodeling heart manifests pronounced heterogeneity in myocardial bioenergetics with most severe alterations in BZ. Cell therapy may effectively improve BZ myocardial bioenergetics.

scholarly journals Opportunities for Antibody Discovery Using Human Pluripotent Stem Cells: Conservation of Oncofetal Targets

2019 ◽  
Vol 20 (22) ◽  
pp. 5752 ◽  
Author(s):  
Heng Liang Tan ◽  
Andre Choo
Keyword(s):  
Stem Cells ◽  
Cancer Cells ◽  
Pluripotent Stem Cells ◽  
Disease Modeling ◽  
Embryonic Stem ◽  
Oncofetal Antigens ◽  
Antibody Discovery ◽  
Induced Pluripotent ◽  
New Biomarkers

Pluripotent stem cells (PSCs) comprise both embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). The application of pluripotent stem cells is divided into four main areas, namely: (i) regenerative therapy, (ii) the study and understanding of developmental biology, (iii) drug screening and toxicology and (iv) disease modeling. In this review, we describe a new opportunity for PSCs, the discovery of new biomarkers and generating antibodies against these biomarkers. PSCs are good sources of immunogen for raising monoclonal antibodies (mAbs) because of the conservation of oncofetal antigens between PSCs and cancer cells. Hence mAbs generated using PSCs can potentially be applied in two different fields. First, these mAbs can be used in regenerative cell therapy to characterize the PSCs. In addition, the mAbs can be used to separate or eliminate contaminating or residual undifferentiated PSCs from the differentiated cell product. This step is critical as undifferentiated PSCs can form teratomas in vivo. The mAbs generated against PSCs can also be used in the field of oncology. Here, novel targets can be identified and the mAbs developed as targeted therapy to kill the cancer cells. Conversely, as new and novel oncofetal biomarkers are discovered on PSCs, cancer mAbs that are already approved by the FDA can be repurposed for regenerative medicine, thus expediting the route to the clinics.

scholarly journals Differentiation of human induced pluripotent stem cells into functional airway epithelium

2020 ◽  
Author(s):  
Engi Ahmed ◽  
Mathieu Fieldes ◽  
Chloé Bourguignon ◽  
Joffrey Mianné ◽  
Aurélie Petit ◽  
...  
Keyword(s):  
Stem Cells ◽  
Drug Discovery ◽  
Induced Pluripotent Stem Cells ◽  
Blood Sample ◽  
Pluripotent Stem Cells ◽  
Bronchial Epithelium ◽  
Neuroendocrine Cells ◽  
Induced Pluripotent

AbstractRationaleHighly reproducible in vitro generation of human bronchial epithelium from pluripotent stem cells is an unmet key goal for drug screening to treat lung diseases. The possibility of using induced pluripotent stem cells (hiPSC) to model normal and diseased tissue in vitro from a simple blood sample will reshape drug discovery for chronic lung, monogenic and infectious diseases.MethodsWe devised a simple and reliable method that drives a blood sample reprogrammed into hiPSC subsequently differentiated within 45 days into air-liquid interface bronchial epithelium (iALI), through key developmental stages, definitive-endoderm (DE) and Ventralized-Anterior-Foregut-Endoderm (vAFE) cells.ResultsReprogramming blood cells from one healthy and 3 COPD patients, and from skin-derived fibroblasts obtained in one PCD patient, succeeded in 100% of samples using Sendai viruses. Mean cell purity at DE and vAFE stages was greater than 80%, assessed by expression of CXCR4 and NKX2.1, avoiding the need of cell sorting. When transferred to ALI conditions, vAFE cells reliably differentiated within 4 weeks into bronchial epithelium with large zones covered by beating ciliated, basal, goblets, club cells and neuroendocrine cells as found in vivo. Benchmarking all culture conditions including hiPSCs adaptation to single-cell passaging, cell density and differentiation induction timing allowed for consistently producing iALI bronchial epithelium from the five hiPSC lines.ConclusionsReliable reprogramming and differentiation of blood-derived hiPSCs into mature and functional iALI bronchial epithelium is ready for wider use and this will allow better understanding lung disease pathogenesis and accelerating the development of novel gene therapies and drug discovery.

scholarly journals Guiding T lymphopoiesis from pluripotent stem cells by defined transcription factors

2019 ◽  
Author(s):  
Rongqun Guo ◽  
Fangxiao Hu ◽  
Qitong Weng ◽  
Cui Lv ◽  
Hongling Wu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Time Window ◽  
Immune Surveillance ◽  
Cell Stage ◽  
Immunodeficient Mice ◽  
Cell Transcriptome ◽  
T Lymphopoiesis

ABSTRACTAchievement of immunocompetent and therapeutic T lymphopoiesis from pluripotent stem cells is a central aim in T cell regenerative medicine. To date, preferentially regenerating T lymphopoiesis in vivo from pluripotent stem cells (PSC) remains a practical challenge. Here we documented that synergistic and transient expression of Runx1 and Hoxa9 restricted in the time window of endothelial to hematopoietic transition and hematopoietic maturation stages induced in vitro from PSC (iR9-PSC) preferentially generated engraftable hematopoietic progenitors capable of homing to thymus and developing into mature T (iT) cells in primary and secondary immunodeficient recipients. Single-cell transcriptome and functional analyses illustrated the cellular trajectory of T lineage induction from PSC, unveiling the T-lineage specification determined at as early as hemogenic endothelial cell stage and identifying the bona fide pre-thymic progenitors. The iT cells distributed normally in central and peripheral lymphoid organs and exhibited abundant TCRαβ repertoire. The regenerative T lymphopoiesis rescued the immune-surveillance ability in immunodeficient mice. Furthermore, gene-edited iR9-PSC produced tumor-specific-T cells in vivo that effectively eradicated tumor cells. This study provides insight into universal generation of functional and therapeutic T lymphopoiesis from the unlimited and editable PSC source.

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