The Human Mesenchymal Stem Cells and the Chick Embryo Chorioallantoic Membrane: The Key and the Lock in Revealing Vasculogenesis

Comşa, Şerban; Ceauşu, Raluca Amalia; Popescu, Roxana; Cîmpean, Anca Maria; Raica, Marius

doi:10.21873/invivo.11180

Cited by 9 publications

(9 citation statements)

References 20 publications

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“…From a tissue engineering perspective, the CAM contains mesenchymal cells which show ‘stemness’ to differentiate, depending on the environment and factors applied. 82 , 83 These cells are important because they allow the interaction between exogenous cells applied to the CAM and resident avian cells, leading to differentiation towards vascular structures, changes in cell phenotype and tumour cell angiogenic mechanisms to be studied. 82 , 83 The mesenchymal cells within the CAM can also offer insights into cell differentiation and recruitment when acellular constructs are applied to the CAM surface.…”

Section: Bone Tissue Engineeringmentioning

confidence: 99%

Evolving applications of the egg: chorioallantoic membrane assay andex vivoorganotypic culture of materials for bone tissue engineering

2020

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The chick chorioallantoic membrane model has been around for over a century, applied in angiogenic, oncology, dental and xenograft research. Despite its often perceived archaic, redolent history, the chorioallantoic membrane assay offers new and exciting opportunities for material and growth factor evaluation in bone tissue engineering. Currently, superior/improved experimental methodology for the chorioallantoic membrane assay are difficult to identify, given an absence of scientific consensus in defining experimental approaches, including timing of inoculation with materials and the analysis of results. In addition, critically, regulatory and welfare issues impact upon experimental designs. Given such disparate points, this review details recent research using the ex vivo chorioallantoic membrane assay and the ex vivo organotypic culture to advance the field of bone tissue engineering, and highlights potential areas of improvement for their application based on recent developments within our group and the tissue engineering field.

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Section: Bone Tissue Engineeringmentioning

confidence: 99%

Evolving applications of the egg: chorioallantoic membrane assay andex vivoorganotypic culture of materials for bone tissue engineering

2020

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“…Chick embryo chorioallantoic membrane (CAM) is well known as a powerful experimental tool for the study of normal and pathologic angiogenesis, because of its high vascular network [13,14]. Additionally, CAM is an embryonic tissue lacking an immune system and having mesenchymal cells with stem like potential able to differentiate depending on a specific microenvironment [15,16]. Based on the previously described features, CAM is a reliable in vivo model for testing the behavior of normal and pathologic tissues (as cultured cells or malignant tumors) [17,18], of different drugs and antibodies [19,20], or of a variety of biomaterials implanted on its surface [21,22].…”

Section: Introductionmentioning

confidence: 99%

Hyaluronic Acid/Bone Substitute Complex Implanted on Chick Embryo Chorioallantoic Membrane Induces Osteoblastic Differentiation and Angiogenesis, but not Inflammation

Cirligeriu

Cîmpean

Călniceanu

et al. 2018

IJMS

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Microscopic and molecular events related to alveolar ridge augmentation are less known because of the lack of experimental models and limited molecular markers used to evaluate this process. We propose here the chick embryo chorioallantoic membrane (CAM) as an in vivo model to study the interaction between CAM and bone substitutes (B) combined with hyaluronic acid (BH), saline solution (BHS and BS, respectively), or both, aiming to point out the microscopic and molecular events assessed by Runt-related transcription factor 2 (RUNX 2), osteonectin (SPARC), and Bone Morphogenic Protein 4 (BMP4). The BH complex induced osteoprogenitor and osteoblastic differentiation of CAM mesenchymal cells, certified by the RUNX2 +, BMP4 +, and SPARC + phenotypes capable of bone matrix synthesis and mineralization. A strong angiogenic response without inflammation was detected on microscopic specimens of the BH combination compared with an inflammatory induced angiogenesis for the BS and BHS combinations. A multilayered organization of the BH complex grafted on CAM was detected with a differential expression of RUNX2, BMP4, and SPARC. The BH complex induced CAM mesenchymal cells differentiation through osteoblastic lineage with a sustained angiogenic response not related with inflammation. Thus, bone granules resuspended in hyaluronic acid seem to be the best combination for a proper non-inflammatory response in alveolar ridge augmentation. The CAM model allows us to assess the early events of the bone substitutes–mesenchymal cells interaction related to osteoblastic differentiation, an important step in alveolar ridge augmentation.

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“…On the other hand, hMSC induced a more intense angiogenic response, but a reduced vasculogenic reaction. Interestingly, when implanted alone onto CAM, hMSC determined an intense vasculogenic reaction, in addition to the angiogenic response (12), which means that MCF-7 have the ability to modulate the involvement of hMSC in neovessel formation. hMSC were demonstrated to enhance the de novo formation of stable vasculature by endothelial colony-forming cells in surrogate models of vasculogenesis in vitro and in vivo (3), in our study cMSC being the source for the endothelial colony-forming cells.…”

Section: Discussionmentioning

confidence: 99%

“…Using the CAM model, we demonstrated that MCF-7 seeded onto CAM recruit the mesenchymal cells from the CAM mesoderm and induce their differentiation towards myofibroblast-like or vasculogenic lineage, turning the mesoderm of the CAM into a surrogate tumor stroma (11). Further on, after the implantation onto CAM, hMSC induce vasculogenesis, by switching to an endothelial-like nonproliferative phenotype, but also by stimulating the chicken MSC from the mesoderm (cMSC) to acquire a vasculogenic and pericyte-like phenotype and to organize into cord/capillary like structures (CLS) (12).…”

mentioning

confidence: 99%

The MSC-MCF-7 Duet Playing Tumor Vasculogenesis and Angiogenesis onto the Chick Embryo Chorioallantoic Membrane

Comşa

CeauȘu

Popescu

et al. 2020

In Vivo

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Background/Aim: Human mesenchymal stem cells (hMSC) represent a versatile cell population, able to modulate the tumor microenvironment. Our aim was to recreate an open scene for the in vivo interaction between hMSC and the MCF-7 breast cancer cells , in order to enlighten the intimate involvement of hMSC in tumor vasculogenesis and angiogenesis. Materials and Methods: hMSC and MCF-7 were seeded onto the chick embryo chorioallantoic membrane (CAM) and incubated for 7 days. Consecutively, the morphology and the immunohistochemical profile of CAM were assessed. Results: Following this complex interaction, MCF-7 acquired a more aggressive phenotype, hMSC switched to a vascular precursor phenotype, while CAM underwent a major reset to an earlier stage, with hotspots of angiogenesis, vasculogenesis and hematopoiesis. Conclusion: The hallmark of this study was the establishment of a veritable in vivo experimental model of MSC involvement in tumor vasculogenesis and angiogenesis, allowing further analysis in the field.As tumor vasculature has been thought to emerge by expansion of the host vasculature through postnatal sprouting of endothelial cells (angiogenesis), it was proposed that inhibiting angiogenesis would stop tumor growth, but it turned out that tumor vessels form through vasculogenesis, rather than through angiogenesis, the process involving circulating bone marrow-derived endothelial precursors rather than mature endothelial cells (1).Lately, mesenchymal stem cells (MSC) have generated substantial interest in the medical areas of transplant, regenerative medicine and cancer treatment because of their multi-potency and multi-functionality. MSC are a heterogeneous subset of stromal cells present in several tissues including bone marrow, bone, adipose tissue, skin, kidney, umbilical cord and placenta (2).MSC are localized in the vascular niche in bone marrow, but also found as MSC-like cells around adult vessels and there is substantial evidence that they play a pivotal role in regulating blood vessel formation and function through multiple mechanisms such as vasculogenesis, arteriogenesis and angiogenesis (3).While MSC differentiation towards vascular cell lineages and their incorporation into a growing vessel wall is rather ill-defined, their important contribution to promoting postnatal vascularization during ischemic myocardial tissue regeneration and tumor vasculogenesis is becoming increasingly recognized (4). It seems that hypoxia serves to enhance the differentiation of MSC towards the endothelial phenotype. Additionally, a revised understanding of MSCderived neovascularization contextualizes their behavior and utility as a hybrid endothelial-stromal cell type, with mixed characteristics of both populations (5).Currently, the role of MSC in carcinogenesis is a matter of controversy. It has been reported that they favor tumor growth due to the immunosuppression they induce. Also, MSC could enhance tumor metastatic potential since they induce epithelial-to-mesenchymal transition (EMT). Other results prove...

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The Human Mesenchymal Stem Cells and the Chick Embryo Chorioallantoic Membrane: The Key and the Lock in Revealing Vasculogenesis

Abstract: Abstract. Background

Cited by 9 publications

References 20 publications

Evolving applications of the egg: chorioallantoic membrane assay andex vivoorganotypic culture of materials for bone tissue engineering

Evolving applications of the egg: chorioallantoic membrane assay andex vivoorganotypic culture of materials for bone tissue engineering

Hyaluronic Acid/Bone Substitute Complex Implanted on Chick Embryo Chorioallantoic Membrane Induces Osteoblastic Differentiation and Angiogenesis, but not Inflammation

The MSC-MCF-7 Duet Playing Tumor Vasculogenesis and Angiogenesis onto the Chick Embryo Chorioallantoic Membrane

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