scholarly journals 3D culture technologies of cancer stem cells: promising ex vivo tumor models

2020 ◽  
Vol 11 ◽  
pp. 204173142093340 ◽  
Author(s):  
Chengye Zhang ◽  
Zhaoting Yang ◽  
Da-Long Dong ◽  
Tae-Su Jang ◽  
Jonathan C. Knowles ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Ex Vivo ◽  
Three Dimensional ◽  
3D Culture ◽  
Cell Matrix ◽  
Culture Models ◽  
Three Dimensional Culture ◽  
Three Dimensional Models

Cancer stem cells have been shown to be important in tumorigenesis processes, such as tumor growth, metastasis, and recurrence. As such, many three-dimensional models have been developed to establish an ex vivo microenvironment that cancer stem cells experience under in vivo conditions. Cancer stem cells propagating in three-dimensional culture systems show physiologically related signaling pathway profiles, gene expression, cell–matrix and cell–cell interactions, and drug resistance that reflect at least some of the tumor properties seen in vivo. Herein, we discussed the presently available Cancer stem cell three-dimensional culture models that use biomaterials and engineering tools and the biological implications of these models compared to the conventional ones.

scholarly journals ID: 1023 All-trans retinoic acid targets gastric cancer stem cells and inhibits patient-derived gastric carcinoma tumor growth

2017 ◽  
Vol 4 (S) ◽  
pp. 98
Author(s):  
P H Nguyen ◽  
J Giraud ◽  
C Staedel ◽  
L Chambonnier ◽  
P Dubus ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Gastric Carcinoma ◽  
Tumor Growth ◽  
Cell Cycle Progression ◽  
3D Culture ◽  
All Trans Retinoic Acid

Gastric carcinoma is the third leading cause of cancer-related death worldwide. This cancer, most of the time metastatic, is essentially treated by surgery associated with conventional chemotherapy, and has a poor prognosis. The existence of cancer stem cells (CSC) expressing CD44 and a high aldehyde dehydrogenase (ALDH) activity has recently been demonstrated in gastric carcinoma and has opened new perspectives to develop targeted therapy. In this study, we evaluated the effects of all-transretinoic acid (ATRA) on CSCs in human gastric carcinoma. ATRA effects were evaluated on the proliferation and tumorigenic properties of gastric carcinoma cells from patient-derived tumors and cell lines in conventional 2D cultures, in 3D culture systems (tumorsphere assay) and in mouse xenograft models. ATRA inhibited both tumorspheres initiation and growth in vitro, which was associated with a cell-cycle arrest through the upregulation of cyclin-dependent kinase (CDK) inhibitors and the downregulation of cell-cycle progression activators. More importantly, ATRA downregulated the expression of the CSC markers CD44 and ALDH as well as stemness genes such as Klf4 and Sox2 and induced differentiation of tumorspheres. Finally, 2 weeks of daily ATRA treatment were sufficient to inhibit gastric tumor progression in vivo, which was associated with a decrease in CD44, ALDH1, Ki67 and PCNA expression in the remaining tumor cells. Administration of ATRA appears to be a potent strategy to efficiently inhibit tumor growth and more importantly to target gastric CSCs in both intestinal and diffuse types of gastric carcinoma.

scholarly journals Changes in the Transcriptome Profiles of Human Amnion-Derived Mesenchymal Stromal/Stem Cells Induced by Three-Dimensional Culture: A Potential Priming Strategy to Improve Their Properties

2022 ◽  
Vol 23 (2) ◽  
pp. 863
Author(s):  
Alessia Gallo ◽  
Nicola Cuscino ◽  
Flavia Contino ◽  
Matteo Bulati ◽  
Mariangela Pampalone ◽  
...  
Keyword(s):  
Stem Cells ◽  
Three Dimensional ◽  
3D Culture ◽  
Therapeutic Effects ◽  
Rna Seq ◽  
Human Amnion ◽  
Cell Based Therapy ◽  
Therapeutic Properties ◽  
Stromal Stem Cells

Mesenchymal stromal/stem cells (MSCs) are believed to function in vivo as a homeostatic tool that shows therapeutic properties for tissue repair/regeneration. Conventionally, these cells are expanded in two-dimensional (2D) cultures, and, in that case, MSCs undergo genotypic/phenotypic changes resulting in a loss of their therapeutic capabilities. Moreover, several clinical trials using MSCs have shown controversial results with moderate/insufficient therapeutic responses. Different priming methods were tested to improve MSC effects, and three-dimensional (3D) culturing techniques were also examined. MSC spheroids display increased therapeutic properties, and, in this context, it is crucial to understand molecular changes underlying spheroid generation. To address these limitations, we performed RNA-seq on human amnion-derived MSCs (hAMSCs) cultured in both 2D and 3D conditions and examined the transcriptome changes associated with hAMSC spheroid formation. We found a large number of 3D culture-sensitive genes and identified selected genes related to 3D hAMSC therapeutic effects. In particular, we observed that these genes can regulate proliferation/differentiation, as well as immunomodulatory and angiogenic processes. We validated RNA-seq results by qRT-PCR and methylome analysis and investigation of secreted factors. Overall, our results showed that hAMSC spheroid culture represents a promising approach to cell-based therapy that could significantly impact hAMSC application in the field of regenerative medicine.

Magnetically actuated microrobots as a platform for stem cell transplantation

2019 ◽  
Vol 4 (30) ◽  
pp. eaav4317 ◽  
Author(s):  
Sungwoong Jeon ◽  
Sangwon Kim ◽  
Shinwon Ha ◽  
Seungmin Lee ◽  
Eunhee Kim ◽  
...  
Keyword(s):  
Stem Cells ◽  
Brain Slice ◽  
Ex Vivo ◽  
Three Dimensional ◽  
Magnetically Actuated ◽  
Magnetic Microrobots ◽  
Hippocampal Neural Stem Cells ◽  
Human Nose

Magnetic microrobots were developed for three-dimensional culture and the precise delivery of stem cells in vitro, ex vivo, and in vivo. Hippocampal neural stem cells attached to the microrobots proliferated and differentiated into astrocytes, oligodendrocytes, and neurons. Moreover, microrobots were used to transport colorectal carcinoma cancer cells to tumor microtissue in a body-on-a-chip, which comprised an in vitro liver-tumor microorgan network. The microrobots were also controlled in a mouse brain slice and rat brain blood vessel. Last, microrobots carrying mesenchymal stem cells derived from human nose were manipulated inside the intraperitoneal cavity of a nude mouse. The results indicate the potential of microrobots for the culture and delivery of stem cells.

scholarly journals A triple-drug nanotherapy to target breast cancer cells, cancer stem cells, and tumor vasculature

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sara El-Sahli ◽  
Khang Hua ◽  
Andrew Sulaiman ◽  
Jason Chambers ◽  
Li Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Ex Vivo ◽  
Chemotherapeutic Agents ◽  
Hybrid Nanoparticles ◽  
Cancer Drug ◽  
Vascular Disrupting Agent

AbstractTriple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, accounting for the majority of breast cancer-related death. Due to the lack of specific therapeutic targets, chemotherapeutic agents (e.g., paclitaxel) remain the mainstay of systemic treatment, but enrich a subpopulation of cells with tumor-initiating capacity and stem-like characteristics called cancer stem cells (CSCs); thus development of a new and effective strategy for TNBC treatment is an unmet medical need. Cancer nanomedicine has transformed the landscape of cancer drug development, allowing for a high therapeutic index. In this study, we developed a new therapy by co-encapsulating clinically approved drugs, such as paclitaxel, verteporfin, and combretastatin (CA4) in polymer-lipid hybrid nanoparticles (NPs) made of FDA-approved biomaterials. Verteporfin is a drug used in the treatment of macular degeneration and has recently been found to inhibit the Hippo/YAP (Yes-associated protein) pathway, which is known to promote the progression of breast cancer and the development of CSCs. CA4 is a vascular disrupting agent and has been tested in phase II/III of clinical trials. We found that our new three drug-NP not only effectively inhibited TNBC cell viability and cell migration, but also significantly diminished paclitaxel-induced and/or CA4-induced CSC enrichment in TNBC cells, partially through inhibiting the upregulated Hippo/YAP signaling. Combination of verteporfin and CA4 was also more effective in suppressing angiogenesis in an in vivo zebrafish model than single drug alone. The efficacy and application potential of our triple drug-NPs were further assessed by using clinically relevant patient-derived xenograft (PDX) models. Triple drug-NP effectively inhibited the viability of PDX organotypic slide cultures ex vivo and stopped the growth of PDX tumors in vivo. This study developed an approach capable of simultaneously inhibiting bulk cancer cells, CSCs, and angiogenesis.

scholarly journals The Molecular Basis of Different Approaches for the Study of Cancer Stem Cells and the Advantages and Disadvantages of a Three-Dimensional Culture

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2615
Author(s):  
Danila Cianciosi ◽  
Johura Ansary ◽  
Tamara Y. Forbes-Hernandez ◽  
Lucia Regolo ◽  
Denise Quinzi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Molecular Basis ◽  
Myeloid Leukemia ◽  
Three Dimensional ◽  
Specific Cell ◽  
Advantages And Disadvantages ◽  
Tumorigenic Potential ◽  
Three Dimensional Culture ◽  
Specific Cell Surface

Cancer stem cells (CSCs) are a rare tumor subpopulation with high differentiation, proliferative and tumorigenic potential compared to the remaining tumor population. CSCs were first discovered by Bonnet and Dick in 1997 in acute myeloid leukemia. The identification and isolation of these cells in this pioneering study were carried out through the flow cytometry, exploiting the presence of specific cell surface molecular markers (CD34+/CD38−). In the following years, different strategies and projects have been developed for the study of CSCs, which are basically divided into surface markers assays and functional assays; some of these techniques also allow working with a cellular model that better mimics the tumor architecture. The purpose of this mini review is to summarize and briefly describe all the current methods used for the identification, isolation and enrichment of CSCs, describing, where possible, the molecular basis, the advantages and disadvantages of each technique with a particular focus on those that offer a three-dimensional culture.

scholarly journals Lin28A Promotes the Amplification and Cancer Stemness of Lung Cancer Cells Via Activating MAPK Pathway Dependent on Let-7c Functions

2021 ◽  
Author(s):  
Rui Zhang ◽  
Pengpeng Liu ◽  
Xiao Zhang ◽  
Yingnan Ye ◽  
Jinpu Yu
Keyword(s):  
Lung Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Culture System ◽  
3D Culture ◽  
Mapk Signaling ◽  
Cancer Stemness ◽  
Over Expression ◽  
3D Culture System

Abstract Background: Metastasis and relapse of lung cancer are the main cause of disease-related deaths. It’s reported that tumor metastasis and relapse originated from cancer stem cells (CSCs) which possess more potential in proliferation and invasion. In our previous studies, we established a conditional BME-based three-dimensional culture (3D culture) system to mimic the growth environment in vivo and further amplified lung cancer stem cells (LCSCs) in our system. However, the molecular mechanisms of the amplification and development of LCSCs in our 3D culture system are still not very clear. Methods: We tested the expression of Lin28 and let7 by western blot and qPCR, and constructed A549 cells either knockdown of Lin28 or overexpression of let7, followed by investigating the expression of stemness markers by flow cytometry and qPCR, and stem cell like phenotypes including cell proliferation, colony formation, mammosphere culture, cell apoptosis, migration, invasion and drug resistance in vitro, as well as tumorigenicity in vivo. Results: Here we observed Lin28A/let-7c was dysregulated in LCSCs both from the 3D culture system and from lung cancer tissues. Further, the abnormal expression of Lin28A/let-7c was correlated with poor survival outcomes. We found over-expression let-7c inhibited the maintenance of LCSC properties, while the results for knockdown of Lin28A showed Lin28A was critical for the enrichment and amplification of LCSCs via MAPK signaling pathway. Importantly, we found that either knockdown of Lin28A or over-expression of let-7c inhibited carcinogenesis and disrupted LCSC expansion in vivo. Conclusions: Our study uncovered the functions and mechanisms of the "Lin28A/let-7c/MAPK" signaling pathway in promoting the amplification and cancer stemness of LCSCs, which might be a potential therapeutic target for lung cancer therapy by reducing and even eliminating LCSCs in the future.

scholarly journals 3D Organoid Culture From Adult Salivary Gland Tissues as an ex vivo Modeling of Salivary Gland Morphogenesis

2021 ◽  
Vol 9 ◽  
Author(s):  
Donghyun Kim ◽  
Yeo-Jun Yoon ◽  
Dojin Choi ◽  
Jisun Kim ◽  
Jae-Yol Lim
Keyword(s):  
Salivary Gland ◽  
Culture System ◽  
Ex Vivo ◽  
Three Dimensional ◽  
Underlying Mechanism ◽  
Lumen Formation ◽  
Organoid Culture ◽  
Culture Models ◽  
Gland Morphogenesis

Lumen formation of salivary glands has been investigated using in vivo or ex vivo rudiment culture models. In this study, we used a three-dimensional (3D) salivary gland organoid culture system and demonstrated that lumen formation could be recapitulated in mouse SMG organoids. In our organoid culture system, lumen formation was induced by vasoactive intestinal peptide and accelerated by treatment with RA. Furthermore, lumen formation was observed in branching duct-like structure when cultured in combination of fibroblast growth factors (FGF) in the presence of retinoic acid (RA). We suggest RA signaling-mediated regulation of VIPR1 and KRT7 as the underlying mechanism for lumen formation, rather than apoptosis in the organoid culture system. Collectively, our results support a fundamental role for RA in lumen formation and demonstrate the feasibility of 3D organoid culture as a tool for studying salivary gland morphogenesis.

scholarly journals A Review on Application of Three Dimensional Culture and Testicular Scaffolds to Induction of in-Vitro Spermatogenesis

2020 ◽  
Author(s):  
Nasrin Majidi Gharenaz ◽  
Mansoureh Movahedin ◽  
Samiyeh Majidi ◽  
Zohreh Mazaheri
Keyword(s):  
Stem Cells ◽  
Three Dimensional ◽  
3D Culture ◽  
Spermatogonial Stem Cells ◽  
Ethical Challenges ◽  
Agar Culture ◽  
In Vitro Spermatogenesis ◽  
Review Study ◽  
Three Dimensional Culture

Introduction: Induction of in vitro spermatogenesis can be useful for infertility treatment in azoospermic patients and those undergoing chemotherapy. Different culture systems have been used to achieve this goal. This review study was performed with the aim to evaluate the application of 3D culture and testicular scaffolds in the establishment of in vitro spermatogenesis. In this review study, the information on the application of 3D culture and testicular scaffolds in induction of in vitro spermatogenesis was searched in databases such as SID, Magiran, PubMed, Irandoc, Iranmedx Scopus, Google Scholar, Web of Science using the keywords of three dimensional culture, testicular scaffold, spermatogenesis, spermatogonial stem cells without time limitation. Data analysis was carried out qualitatively. Finally, 35 papers in English and Persian were used to compile the article. In order to induce of in vitro spermatogenesis, three-dimensional culture methods such as testicular tissue culture, soft agar culture system, natural biomaterial scaffolds such as collagen, and scaffolds derived from decellularized testis have been used. Conclusion: Three-dimensional culture using spermatogonial stem cells and scaffolds can be used in vitro for induction of spermatogenesis, but there are further technical and ethical challenges in the path of fertile sperm production for the treatment of infertility.  

scholarly journals Lipophilic dye-compatible brain clearing technique allowing correlative magnetic resonance/high-resolution fluorescence imaging in rat models of glioblastoma

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Marco Peviani ◽  
Giorgia Spano ◽  
Antonella Pagani ◽  
Gianluca Brugnara ◽  
Cesare Covino ◽  
...  
Keyword(s):  
Stem Cells ◽  
High Resolution ◽  
Cancer Stem Cells ◽  
Ex Vivo ◽  
Rat Models ◽  
Novel Approach ◽  
Clearing Technique ◽  
Confocal Images ◽  
Development And Validation

Abstract In this work we optimized a novel approach for combining in vivo MRI and ex vivo high-resolution fluorescence microscopy that involves: (i) a method for slicing rat brain tissue into sections with the same thickness and spatial orientation as in in vivo MRI, to better correlate in vivo MRI analyses with ex-vivo imaging via scanning confocal microscope and (ii) an improved clearing protocol compatible with lipophilic dyes that highlight the neurovascular network, to obtain high tissue transparency while preserving tissue staining and morphology with no significant tissue shrinkage or expansion. We applied this methodology in two rat models of glioblastoma (GBM; U87 human glioma cells and patient-derived human glioblastoma cancer stem cells) to demonstrate how vital the information retrieved from the correlation between MRI and confocal images is and to highlight how the increased invasiveness of xenografts derived from cancer stem cells may not be clearly detected by standard in vivo MRI approaches. The protocol studied in this work could be implemented in pre-clinical GBM research to further the development and validation of more predictive and translatable MR imaging protocols that can be used as critical diagnostic and prognostic tools. The development of this protocol is part of the quest for more efficacious treatment approaches for this devastating and still uncurable disease. In particular, this approach could be instrumental in validating novel MRI-based techniques to assess cellular infiltration beyond the macroscopic tumor margins and to quantify neo-angiogenesis.

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