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Appearance of extraembryonic tissues and organs in mouse embryos and fetuses. (A-D) Schematic representation of the turning process in mouse between E8.5 and E9.5. As a consequence of the axial rotation, the embryo gets encased in its extraembryonic membranes. Adapted from Kaufman, 1992. (E) An E8.5 mouse conceptus (CD1 outbred strain) dissected free from the decidua and its parietal yolk sac. The visceral yolk sac masks the amnion, the chorion, the allantois and the embryo proper. Scale bar, 250 μm. (F) Another E8.5 mouse embryo after removal of the visceral yolk sac. The amnion, the allantois and the embryo become better visible. The chorion-to which the allantois has fused at this stage-is hidden by the ectoplacental cone. Amnion and chorion are not in physical contact anymore at this stage. The embryo is still in its unturned lordotic position. Anterior is to the left, posterior to the right. (G) An E9.0 mouse embryo in the process of turning. The visceral yolk sac is removed. The amniotic membrane is avascular and transparent. (H) A turned E9.5 embryo. Scale bar (F-H) 500 μm. (I) Lateral view of an E11.5 fetus which is surrounded by its vascularised visceral yolk sac. A rim of parietal yolk sac covering the visceral yolk sac is still visible. For simplicity, the parietal yolk sac was not discussed in the text. It is a transient membrane derived of the mural trophectoderm and the parietal endoderm which is crucial for implantation and nutrition of the early embryo. The parietal yolk sac surrounds initially the whole conceptus. It is not the equivalent of the human primary yolk sac. (J) Dorsal view of E11.5 fetus after removal of the visceral yolk sac. The amnion is clearly visible as an avascular membrane that encases the embryo. The fetus has acquired a typical flexed fetal shape. Scale bar I-J: 1 mm. (K) Schematic representation of the different extraembryonic membranes and their tissue composition at the level of the dotted line in panel I. The top and bottom corresponds to right and left side of the dotted line. Abbreviations: AC, amniotic cavity; Al: allantois; Am: amnion;; AmE: amniotic ectoderm; AmM: amniotic mesoderm; BV: blood vessel; Ch: chorion; CP: chorionic plate; EC: exocoelom; EPC: ectoplacental cone; ExM: extraembryonic mesoderm; PE: parietal endoderm; Pl: Placenta; PYS: parietal yolk sac; RM: Reichert's membrane; TE: trophectoderm; VE: visceral endoderm; VYS: visceral yolk sac; YSC: yolk sac cavity.
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A common characteristic of mammals is the development of extraembryonic supporting tissues and organs that are required for embryonic implantation, survival and development in utero. The amnion is the innermost extraembryonic membrane that eventually surrounds the fetus of amniotes, and contains the amniotic fluid. Next to its function in in utero...
Contexts in source publication
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... the egg cylinder the chorion is pushed proximally and amniotic and chorionic mem- branes divide the proamniotic cavity into amniotic, exocoelomic and ectoplacental cavity (Fig. 3 C,D). When chorion and ectopla- cental cone meet, they fuse to form the fetal part of the placenta. When the embryo displays 6-8 somites (around E8.5), it starts turning (Fig. 4 A-H) and becomes progressively transformed from a lordotic (Fig. 4 A,B,F) position into the regular flexed fetal position (Fig. 4 D,H) which is observed in most chordates. As a result of this turning process, which is completed at the 14-16 somite stage, the ectoderm acquires an exterior location and the embryo becomes entirely ...
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... chorionic mem- branes divide the proamniotic cavity into amniotic, exocoelomic and ectoplacental cavity (Fig. 3 C,D). When chorion and ectopla- cental cone meet, they fuse to form the fetal part of the placenta. When the embryo displays 6-8 somites (around E8.5), it starts turning (Fig. 4 A-H) and becomes progressively transformed from a lordotic (Fig. 4 A,B,F) position into the regular flexed fetal position (Fig. 4 D,H) which is observed in most chordates. As a result of this turning process, which is completed at the 14-16 somite stage, the ectoderm acquires an exterior location and the embryo becomes entirely enwrapped by its amnion and visceral yolk sac (Kaufman, 1992). Due to the ...
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... exocoelomic and ectoplacental cavity (Fig. 3 C,D). When chorion and ectopla- cental cone meet, they fuse to form the fetal part of the placenta. When the embryo displays 6-8 somites (around E8.5), it starts turning (Fig. 4 A-H) and becomes progressively transformed from a lordotic (Fig. 4 A,B,F) position into the regular flexed fetal position (Fig. 4 D,H) which is observed in most chordates. As a result of this turning process, which is completed at the 14-16 somite stage, the ectoderm acquires an exterior location and the embryo becomes entirely enwrapped by its amnion and visceral yolk sac (Kaufman, 1992). Due to the axial rotation, the amnion becomes positioned between the visceral ...
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... in most chordates. As a result of this turning process, which is completed at the 14-16 somite stage, the ectoderm acquires an exterior location and the embryo becomes entirely enwrapped by its amnion and visceral yolk sac (Kaufman, 1992). Due to the axial rotation, the amnion becomes positioned between the visceral yolk sac and the fetus (Figs. 4, 5). It is of note that from E7.5 onwards, amnion and chorion have become two completely separate membranes that are no longer in contact with each other (Fig. 3 C,D, 4 A,F), and hence the rodent amnion does not become incorporated in the placenta. The amnion remains through gestation a very thin and avascular membrane (Fig. 5). Like in ...
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... et al., 1986). Fourthly, the origin of the murine amniotic mesoderm is less controversial; it is definitely the extraembryonic mesoderm, which is an epiblast derived tissue (Lawson et al., 1991;Smith et al., 1994). Fifthly, the murine amnion is a simple bilayered membrane that remains during the whole gestation surrounded by the visceral yolk sac (Figs. 4, 5). It is plausible that the visceral yolk sac fulfils in rodents to a large extend the shock barrier function of the amnion in primates. Sixthly, the murine amnion does not make contact with the chorion and therefore does not become incorporated into the ...
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... bar: 100 μm. (C) Magnification of the amnion represented in C. Scale bar: 25 μm. (D) Schematic represen- tation of the visceral yolk sac at E9.5. The murine visceral yok sac consists of extraembryonic endoderm and extraembryonic mesoderm. The latter is the layer in which blood islands are formed at E7.5 ( Palis et al., 1995) (not represented in Fig. ...
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... sac that does not surround the fetus; while the amniotic sac of rodents surrounds the fetus closely and is itself still enclosed completely by the visceral yolk sac. The latter contains the exocoelomic fluid. Moreover, the rodent amnion never fuses to the chorion. The chorion becomes incorporated completely in the chorionic plate of the placenta (Fig. ...
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Amnion-derived mesenchymal stem cells (AMSCs) are multipotent cells with an enhanced ability to differentiate into multiple lineages. AMSCs can be acquired through noninvasive methods, and therefore are exempt from the typical ethical issues surrounding stem cell use. The objective of this study was to isolate and characterize AMSCs from a cat amni...
ABSTRACT In recent years, a constant growth of knowledge and clinical applications of stem cells have been observed. Mesenchymal stromal cells, also described as mesenchymal stem cells (MSCs) represent a particular cell type for research and therapy because of their ability to differentiate into mesodermal lineage cells. The most investigated sourc...
Citations
... Arguably, the most notable advantage of ASCs is their suspected lack of tumorgenicity. Numerous studies have analyzed the tumor-forming potential of ASCs in vivo and have shown no tumor formation [68][69][70][71]. In addition, Phermthai et al. used karyotype analysis to show that ASCs display high chromosomal stability [72]. ...
Bone/fracture healing is a complex process with different steps and four basic tissue layers being affected: cortical bone, periosteum, fascial tissue surrounding the fracture, and bone marrow. Stem cells and their derivatives, including embryonic stem cells, induced pluripotent stem cells, mesenchymal stem cells, hematopoietic stem cells, skeletal stem cells, and multipotent stem cells, can function to artificially introduce highly regenerative cells into decrepit biological tissues and augment the healing process at the tissue level. Stem cells are molecularly and functionally indistinguishable from standard human tissues. The widespread appeal of stem cell therapy lies in its potential benefits as a therapeutic technology that, if harnessed, can be applied in clinical settings. This review aims to establish the molecular pathophysiology of bone healing and the current stem cell interventions that disrupt or augment the bone healing process and, finally, considers the future direction/therapeutic options related to stem cells and bone healing.
... Arguably, the most notable advantage of ASCs is their suspected lack of tumorgenicity. Numerous studies have analyzed the tumor-forming potential of ASCs in vivo and have shown no tumor formation [67][68][69][70]. In addition, Phermthai et al. used karyotype analysis to show that ASCs display high chromosomal stability [71]. ...
Bone/fracture healing is a complex process with different steps and four basic tissue layers being affected: cortical bone, periosteum, fascial tissue surrounding the fracture, and bone marrow. Stem cells and their derivatives, including embryonic stem cells, induced pluripotent stem cells, mesenchymal stem cells, hematopoietic stem cells, skeletal stem cells, and multipotent stem cells, can function to artificially introduce highly regenerative cells into decrepit biological tissues and augment the healing process at the tissue level. Stem cells are molecularly and functionally indistinguishable from standard human tissues. The widespread appeal of stem cell therapy lies in its potential benefits as a therapeutic technology that, if harnessed, can be applied in clinical settings. This review aims to establish the molecular pathophysiology of bone healing, the current stem cell interventions that disrupt or augment the bone healing process, and finally, consider the future direction/therapeutic options related to stem cells and bone healing.
... Actualmente muchos investigadores consideran que, al igual que el corion, el conectivo amniótico se deriva del trofoectodermo y de la somatopleura del mesodermo extraembrionario 32,33 . Sin embargo existe una tercera opción por considerar, propuesta por el grupo de Dobreva en 2010, la posibilidad de que el origen del mesodermo extraembrionario sea más complejo y no excluya que tenga origen, tanto del hipoblasto como del epiblasto 34 . Finalmente, entre los 30-35 dpf el amnios se encuentra constituido por las tres capas características de su madurez, EA, capa compacta, capa de fibroblastos y zona esponjosa en contacto con el corion. ...
The amniotic membrane, located on the inner side of the fetal placenta, has been the subject of multiple investigations to try to elucidate its embryological role and its therapeutic cellular potential. Currently, the limitations of the study in human fetuses mean that part of its functioning is unknown, however, some clinical and basic studies shed light on its role in modern medicine. A bibliographic review of the literature was carried out from 1960 to 2022, using databases such as PubMed, SciELO and Scopus, including a total of 50 articles and two embryology texts. The objective of this narrative review was to synthesize information on angiogenesis and its clinical importance. The information collected made it possible to show that the healing properties of the fetal skin are due to intrinsic factors of the fetus, and that human amniotic epithelial cells have a differentiation similar to embryonic stem cells, with the differentiation capacity similar to that of mesenchymal cells, highlighting their clinical importance due to their regenerative characteristics. In conclusion, human embryonic development remains relatively inexplicable, but its knowledge has allowed great advances, which could be useful in regeneration therapies, repair of injured tissues and organs.
... The AF volume also changes during pregnancy, increasing between gestational days GD-9.5 and 16 and decreasing on GD 18.5 [9]. The metabolic functions of AF may vary between rodents and humans partly due to differences in placental structure and function, as well as maternal physiology [10]. ...
... With the exception of AF-MSCs, CP-MSCs, and umbilical cord blood-derived cells, the here discussed fetal stem cells exhibit markers and features of both, multipotency and pluripotency, what does not necessarily imply that they can develop into every type of tissue. Broadly multipotent fetal stem cells are developmentally and operationally located between ESCs/iPSCs and adult stem cells (Figs. 1 and 2) [33][34][35][36][37][38]. ...
... It is therefore not surprising that the stem cell entities, which are functionally engaged with these fetal tissues, must display self-renewal, a high differentiation potential, and eminent paracrine properties. In line with that, there is broad consensus that the remarkable properties of AM-MSCs, AECs, CL-MSCs, WJ-MSCs, UCB-MSCs, UCB-HSCs, CP-MSCs, and CV-MSCs essentially reflect their biological roles in the according tissues of the placenta and fetal annexes (Fig. 2, Table 1) [32][33][34][35][36]38]. ...
Due to the limited accessibility of the in vivo situation, the scarcity of the human tissue, legal constraints, and ethical considerations, the underlying molecular mechanisms of disorders, such as preeclampsia, the pathological consequences of fetomaternal microchimerism, or infertility, are still not fully understood. And although substantial progress has already been made, the therapeutic strategies for reproductive system diseases are still facing limitations. In the recent years, it became more and more evident that stem cells are powerful tools for basic research in human reproduction and stem cell-based approaches moved into the center of endeavors to establish new clinical concepts. Multipotent fetal stem cells derived from the amniotic fluid, amniotic membrane, chorion leave, Wharton´s jelly, or placenta came to the fore because they are easy to acquire, are not associated with ethical concerns or covered by strict legal restrictions, and can be banked for autologous utilization later in life. Compared to adult stem cells, they exhibit a significantly higher differentiation potential and are much easier to propagate in vitro. Compared to pluripotent stem cells, they harbor less mutations, are not tumorigenic, and exhibit low immunogenicity. Studies on multipotent fetal stem cells can be invaluable to gain knowledge on the development of dysfunctional fetal cell types, to characterize the fetal stem cells migrating into the body of a pregnant woman in the context of fetomaternal microchimerism, and to obtain a more comprehensive picture of germ cell development in the course of in vitro differentiation experiments. The in vivo transplantation of fetal stem cells or their paracrine factors can mediate therapeutic effects in preeclampsia and can restore reproductive organ functions. Together with the use of fetal stem cell-derived gametes, such strategies could once help individuals, who do not develop functional gametes, to conceive genetically related children. Although there is still a long way to go, these developments regarding the usage of multipotent fetal stem cells in the clinic should continuously be accompanied by a wide and detailed ethical discussion.
... Despite the advantage of rabbit models for studying the therapeutic effects of allogeneic MSCs from neonatal tissues, only one experimental attempt to isolate and cultivate MSCs from the umbilical cord of rabbits is described [3]. The methods of isolation and characteristics of the stem cell populations from the human amnion are well described in the literature, similar data are also known for the amnion of mice [4]. However, for rabbits, this issue is practically unexplored. ...
Despite the advantages of studying the therapeutic potential of autologous and allogeneic mesenchymal stem cells (MSCs) on the rabbit model, the cultivation of rabbit amnion MSCs has not been described in the literature.
Aim: To study the possibility of isolation, multiplication, and cryopreservation of amnion-derived rabbit MSCs.
Methods: The amniotic membrane was obtained surgically. Both enzymatic and explant methods of cell isolation have been tested. The obtained primary cultures were passed, and their proliferation capacity and morphology characteristics were studied.
Results: The viable clones were obtained on the 2nd day of cultivation using an enzymatic method. At all passages, the cells showed adhesion to the culture plastic and fibroblast-like morphology. At the first and second passages, after 7 days of cultivation, the population doubling occurred 4.4 and 4.3 times, respectively. Evaluation of the viability after cryopreservation showed that after thawing, more than 90 % of cells were alive, and 4.3 doubling occurred in 7 days of cultivation. No cells with the atypical phenotype were detected during cultivation. Conclusions: The methods of extraction, multiplication, and cryopreservation of MSCs-like rabbit amnion cells were optimized. This can promote further studies of the MSCs characteristics and regenerative potential.
... The Placenta is a unique organ existing for a short period in the body during gestation and is fundamental for appropriate fetal development. It is a site for the expression of many antigens and molecular markers shared by many cancer cell types [13][14][15][16] and hosts a collection of cells with stem cell properties [17]. Human amniotic epithelial cells (hAEC) are among placenta-derived cells with known stem celllike and immunomodulatory properties [18][19][20]. ...
We identified here mechanism by which hAECs exert their anti-cancer effects. We showed that vaccination with live hAEC conferred effective protection against murine colon cancer and melanoma but not against breast cancer in an orthotopic cancer cell inoculation model. hAEC induced strong cross-reactive antibody response to CT26 cells, but not against B16F10 and 4T1 cells. Neither heterotopic injection of tumor cells in AEC-vaccinated mice nor vaccination with hAEC lysate conferred protection against melanoma or colon cancer. Nano-sized AEC-derived small-extracellular vesicles (sEV) (AD-sEV) induced apoptosis in CT26 cells and inhibited their proliferation. Co-administration of AD-sEV with tumor cells substantially inhibited tumor development and increased CTL responses in vaccinated mice. AD-sEV triggered the Warburg’s effect leading to Arginine consumption and cancer cell apoptosis. Our results clearly showed that it is AD-sEV but not the cross-reactive immune responses against tumor cells that mediate inhibitory effects of hAEC on cancer development. Our results highlight the potential anti-cancer effects of extracellular vesicles derived from hAEC.
... R. Soc. B 377: 20210258 visceral yolk sac ends up encapsulating the amnion and the embryo [10] (figure 1a). The allantois stores waste products but is rather vestigial in eutherians, whereas in egg-laying amniotes, the chorion and the allantois are vital and primarily needed for gas exchange across the eggshell. ...
... B 377: 20210258 9-10 somite stage, the mouse embryo undergoes an 180 o axial rotation (dorsal-ventral) and acquires the typical fetalposition shape. The midgut becomes internalized and the two extraembryonic membranes, the amnion and visceral yolk sac, surround the entire embryo instead of being positioned dorsally from the embryo [10]. ...
The amnion is an extraembryonic tissue that evolutionarily allowed embryos of all amniotes to develop in a transient and local aquatic environment. Despite the importance of this tissue, very little is known about its formation and its molecular characteristics. In this review, we have compared the basic organization of the extraembryonic membranes in amniotes and describe the two types of amniogenesis, folding and cavitation. We then zoom in on the atypical development of the amnion in mice that occurs via the formation of a single posterior amniochorionic fold. Moreover, we consolidate lineage tracing data to better understand the spatial and temporal origin of the progenitors of amniotic ectoderm, and visualize the behaviour of their descendants in the extraembryonic–embryonic junctional region. This analysis provides new insight on amnion development and expansion. Finally, using an online-available dataset of single-cell transcriptomics during the gastrulation period in mice, we provide bioinformatic analysis of the molecular signature of amniotic ectoderm and amniotic mesoderm. The amnion is a tissue with unique biomechanical properties that deserves to be better understood.
This article is part of the theme issue ‘Extraembryonic tissues: exploring concepts, definitions and functions across the animal kingdom’.
... 1,3 In addition, accumulating evidence has shown that the amnion contains mesenchymal stem-like cells with high plasticity. [4][5][6][7] Despite the fact that the amnion is an avascular tissue, amniotic cells are able to differentiate into endothelial cells or cardiomyocytes under a certain condition. [8][9][10] Due to easy availability without ethical issues and low incidence of rejection even if human amniotic cells are transplanted to another person, effective use of the human amnion for regenerative medicine has been expected. ...
... The amniotic membrane consists of two layers of the ectoderm and the mesoderm origin, although its forming process differs depending on the species. 4,15 In chick embryos, the generation of the amnion occurs after gastrulation, with the appearance of the extraembryonic coelomic cavity in the extraembryonic mesoderm at head fold stage. [16][17][18] The coelomic cavity separates the lateral mesoderm into two components, somatic and splanchnic mesoderm. ...
Background
The somatopleure serves as the primordium of the amnion, an extraembryonic membrane surrounding the embryo. Recently, we have reported that amniogenic somatopleural cells (ASCs) not only form the amnion but also migrate into the embryo and differentiate into cardiomyocytes and vascular endothelial cells. However, detailed differentiation processes and final distributions of these intra‐embryonic ASCs (hereafter referred to as iASCs) remain largely unknown.
Results
By quail‐chick chimera analysis, we here show that iASCs differentiate into various cell types including cardiomyocytes, smooth muscle cells, cardiac interstitial cells, and vascular endothelial cells. In the pharyngeal region, they distribute selectively into the thyroid gland and differentiate into vascular endothelial cells to form intra‐thyroid vasculature. Explant culture experiments indicated sequential requirement of fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF) signaling for endothelial differentiation of iASCs. Single‐cell transcriptome analysis further revealed heterogeneity and the presence of hemangioblast‐like cell population within ASCs, with a switch from FGF to VEGF receptor gene expression.
Conclusion
The present study demonstrates novel roles of ASCss especially in heart and thyroid development. It will provide a novel clue for understanding the cardiovascular development of amniotes from embryological and evolutionary perspectives.
... Nevertheless, this still leaves open the problem of distinguishing trophoblast and amnion identity in the more commonly used two-dimensional context of BMP4-treated hPSC. In such analyses, the distinct developmental origins of the amnion should be kept in mind: specifically, that amnion formation occurs within the peri-gastrulation mouse embryo, but in the pre-gastrulation primate embryo [94]. While there is some single cell RNAseq data for amnion from cynomolgus monkey embryos [95], the datasets most commonly used for distinguishing these lineages in the human have been those of Xiang et al. [96], from extended culture human embryos, and Roost et al. [97], from first and second trimester human amnion. ...
The Bone Morphogenetic Protein (BMP) signaling pathway has established roles in early embryonic morphogenesis, particularly in the epiblast. More recently, however, it has also been implicated in development of extraembryonic lineages, including trophectoderm (TE), in both mouse and human. In this review, we will provide an overview of this signaling pathway, with a focus on BMP4, and its role in emergence and development of TE in both early mouse and human embryogenesis. Subsequently, we will build on these in vivo data and discuss the utility of BMP4-based protocols for in vitro conversion of primed vs. naïve pluripotent stem cells (PSC) into trophoblast, and specifically into trophoblast stem cells (TSC). PSC-derived TSC could provide an abundant, reproducible, and ethically acceptable source of cells for modeling placental development.
