scholarly journals Differentiation of cancer stem cells into erythroblasts in the presence of CoCl2

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kazuki Kumon ◽  
Said M. Afify ◽  
Ghmkin Hassan ◽  
Shunsuke Ueno ◽  
Sadia Monzur ◽  
...  
Keyword(s):  
Stem Cells ◽  
Tumor Microenvironment ◽  
Cancer Stem Cells ◽  
Malignant Tumors ◽  
Multilineage Differentiation ◽  
Differentiation Potential ◽  
Hypoxic Conditions ◽  
Induced Pluripotent ◽  
Insight Into ◽  
Runx1 Expression

AbstractCancer stem cells (CSCs) are subpopulations in the malignant tumors that show self-renewal and multilineage differentiation into tumor microenvironment components that drive tumor growth and heterogeneity. In previous studies, our group succeeded in producing a CSC model by treating mouse induced pluripotent stem cells. In the current study, we investigated the potential of CSC differentiation into blood cells under chemical hypoxic conditions using CoCl2. CSCs and miPS-LLCcm cells were cultured for 1 to 7 days in the presence of CoCl2, and the expression of VEGFR1/2, Runx1, c-kit, CD31, CD34, and TER-119 was assessed by RT-qPCR, Western blotting and flow cytometry together with Wright-Giemsa staining and immunocytochemistry. CoCl2 induced significant accumulation of HIF-1α changing the morphology of miPS-LLCcm cells while the morphological change was apparently not related to differentiation. The expression of VEGFR2 and CD31 was suppressed while Runx1 expression was upregulated. The population with hematopoietic markers CD34+ and c-kit+ was immunologically detected in the presence of CoCl2. Additionally, high expression of CD34 and, a marker for erythroblasts, TER-119, was observed. Therefore, CSCs were suggested to differentiate into erythroblasts and erythrocytes under hypoxia. This differentiation potential of CSCs could provide new insight into the tumor microenvironment elucidating tumor heterogenicity.

scholarly journals Metastasis of Cancer Stem Cells Developed in the Microenvironment of Hepatocellular Carcinoma

2019 ◽  
Vol 6 (3) ◽  
pp. 73 ◽  
Author(s):  
Said M. Afify ◽  
Ghmkin Hassan ◽  
Amira Osman ◽  
Anna Sanchez Calle ◽  
Hend M Nawara ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cultured Cells ◽  
Malignant Tumors ◽  
Metastatic Potential ◽  
Metastatic Cells ◽  
Huh7 Cells ◽  
Induced Pluripotent

Metastasis develops when cancer cells spread from the primary site of a malignant tumor to the surrounding and distant tissues, and it is the most critical problem in cancer treatment. Our group developed cancer stem cells (CSCs) from induced pluripotent stem cells (iPSCs) in the presence of a conditioned medium (CM) of cancer-derived cells. The CSCs were characterized by the formation of malignant tumors in vivo, followed by metastasis. In this study, CSCs converted from mouse iPSCs in the presence of CM from hepatocellular carcinoma (HCC) cell line Huh7 cells. These converted cells (miPS-Huh7cm cells) were established as the metastatic cells. The generated CSCs were injected into the liver or spleen of nude mice. Almost one month after transplantation, the tumors were excised, and the primary cultured cells derived from the malignant tumors and metastatic nodules were evaluated by stemness and metastatic markers to compare their differences. The miPS-Huh7cm cells exhibited metastatic potential, and efficiently formed malignant tumors with lung and/or liver lesions in vivo, whereas the injected miPS formed teratoma. The primary cultured cells derived from the malignant tumors and metastatic nodules sustained the expression of stemness markers, such as Nanog, Klf4 and c-Myc, and acquired cancer stem markers, such as CD90, CD44 and ALDH1. Simultaneously, the expression of metastatic markers, such as Slug, Twist1 and vimentin, in primary cells derived from the malignant tumors, was higher than in metastatic nodules. The CSCs derived from iPSCs, forming malignant tumors and displaying high metastasis, will provide a good animal model to study the mechanisms of metastasis.

scholarly journals Hematopoietic Cells Derived from Cancer Stem Cells Generated from Mouse Induced Pluripotent Stem Cells

Cancers ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 82 ◽  
Author(s):  
Ghmkin Hassan ◽  
Said M. Afify ◽  
Neha Nair ◽  
Kazuki Kumon ◽  
Amira Osman ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Cancer Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Malignant Tumors ◽  
White Blood Cells ◽  
Hematopoietic Cells ◽  
Adherent Cells ◽  
Induced Pluripotent

Cancer stem cells (CSCs) represent the subpopulation of cancer cells with the ability to differentiate into other cell phenotypes and initiated tumorigenesis. Previously, we reported generating CSCs from mouse induced pluripotent stem cells (miPSCs). Here, we investigated the ability of the CSCs to differentiate into hematopoietic cells. First, the primary cells were isolated from malignant tumors that were formed by the CSCs. Non-adherent cells (NACs) that arose from adherent cells were collected and their viability, as well as the morphology and expression of hematopoietic cell markers, were analyzed. Moreover, NACs were injected into the tail vein of busulfan conditioned Balb/c nude mice. Finally, CSCs were induced to differentiate to macrophages while using IL3 and SCF. The round nucleated NACs were found to be viable, positive for hematopoietic lineage markers and CD34, and expressed hematopoietic markers, just like homing to the bone marrow. When NACs were injected into mice, Wright–Giemsa staining showed that the number of white blood cells got higher than those in the control mice after four weeks. CSCs also showed the ability to differentiate toward macrophages. CSCs were demonstrated to have the potential to provide progenies with hematopoietic markers, morphology, and homing ability to the bone marrow, which could give new insight into the tumor microenvironment according to the plasticity of CSCs.

scholarly journals Conversion of Stem Cells to Cancer Stem Cells: Undercurrent of Cancer Initiation

Cancers ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 345 ◽  
Author(s):  
Said Afify ◽  
Masaharu Seno
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Malignant Tumors ◽  
The Novel ◽  
Inflammatory Microenvironment ◽  
Differentiated Cells ◽  
Cancer Initiation ◽  
Induced Pluripotent ◽  
Novel Concept ◽  
Exact Origin

Cancer stem cells (CSCs) also known as cancer-initiating cells (CIC), are responsible for the sustained and uncontrolled growth of malignant tumors and are proposed to play significant roles in metastasis and recurrence. Several hypotheses have proposed that the events in either stem and/or differentiated cells, such as genomic instability, inflammatory microenvironment, cell fusion, and lateral gene transfer, should be considered as the possible origin of CSCs. However, until now, the exact origin of CSC has been obscure. The development of induced pluripotent stem cells (iPSCs) in 2007, by Yamanaka’s group, has been met with much fervency and hailed as a breakthrough discovery by the scientific and research communities, especially in regeneration therapy. The studies on the development of CSC from iPSCs should also open a new page of cancer research, which will help in designing new therapies applicable to CSCs. Currently most reviews have focused on CSCs and CSC niches. However, the insight into the niche before the CSC niche should also be of keen interest. This review introduces the novel concept of cancer initiation introducing the conversion of iPSCs to CSCs and proposes a relationship between the inflammatory microenvironment and cancer initiation as the key concept of the cancer-inducing niche responsible for the development of CSC.

scholarly journals Revisiting Cancer Stem Cells as the Origin of Cancer-Associated Cells in the Tumor Microenvironment: A Hypothetical View from the Potential of iPSCs

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 879 ◽  
Author(s):  
Amira Osman ◽  
Said M. Afify ◽  
Ghmkin Hassan ◽  
Xiaoying Fu ◽  
Akimasa Seno ◽  
...  
Keyword(s):  
Stem Cells ◽  
Tumor Microenvironment ◽  
Cancer Stem Cells ◽  
Tumor Growth ◽  
Stromal Cells ◽  
Tumor Development ◽  
Normal Tissues ◽  
Lineage Differentiation ◽  
Tumor Growth And Metastasis ◽  
Induced Pluripotent

The tumor microenvironment (TME) has an essential role in tumor initiation and development. Tumor cells are considered to actively create their microenvironment during tumorigenesis and tumor development. The TME contains multiple types of stromal cells, cancer-associated fibroblasts (CAFs), Tumor endothelial cells (TECs), tumor-associated adipocytes (TAAs), tumor-associated macrophages (TAMs) and others. These cells work together and with the extracellular matrix (ECM) and many other factors to coordinately contribute to tumor growth and maintenance. Although the types and functions of TME cells are well understood, the origin of these cells is still obscure. Many scientists have tried to demonstrate the origin of these cells. Some researchers postulated that TME cells originated from surrounding normal tissues, and others demonstrated that the origin is cancer cells. Recent evidence demonstrates that cancer stem cells (CSCs) have differentiation abilities to generate the original lineage cells for promoting tumor growth and metastasis. The differentiation of CSCs into tumor stromal cells provides a new dimension that explains tumor heterogeneity. Using induced pluripotent stem cells (iPSCs), our group postulates that CSCs could be one of the key sources of CAFs, TECs, TAAs, and TAMs as well as the descendants, which support the self-renewal potential of the cells and exhibit heterogeneity. In this review, we summarize TME components, their interactions within the TME and their insight into cancer therapy. Especially, we focus on the TME cells and their possible origin and also discuss the multi-lineage differentiation potentials of CSCs exploiting iPSCs to create a society of cells in cancer tissues including TME.

Mini Review; Differentiation of Human Pluripotent Stem Cells into Oocytes

2020 ◽  
Vol 15 (4) ◽  
pp. 301-307 ◽  
Author(s):  
Gaifang Wang ◽  
Maryam Farzaneh
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Embryonic Stem ◽  
Human Pluripotent Stem Cells ◽  
Human Oocyte ◽  
Differentiation Potential ◽  
Cell Lineages ◽  
Cell Based Therapy ◽  
Induced Pluripotent

Primary Ovarian Insufficiency (POI) is one of the main diseases causing female infertility that occurs in about 1% of women between 30-40 years of age. There are few effective methods for the treatment of women with POI. In the past few years, stem cell-based therapy as one of the most highly investigated new therapies has emerged as a promising strategy for the treatment of POI. Human pluripotent stem cells (hPSCs) can self-renew indefinitely and differentiate into any type of cell. Human Embryonic Stem Cells (hESCs) as a type of pluripotent stem cells are the most powerful candidate for the treatment of POI. Human-induced Pluripotent Stem Cells (hiPSCs) are derived from adult somatic cells by the treatment with exogenous defined factors to create an embryonic-like pluripotent state. Both hiPSCs and hESCs can proliferate and give rise to ectodermal, mesodermal, endodermal, and germ cell lineages. After ovarian stimulation, the number of available oocytes is limited and the yield of total oocytes with high quality is low. Therefore, a robust and reproducible in-vitro culture system that supports the differentiation of human oocytes from PSCs is necessary. Very few studies have focused on the derivation of oocyte-like cells from hiPSCs and the details of hPSCs differentiation into oocytes have not been fully investigated. Therefore, in this review, we focus on the differentiation potential of hPSCs into human oocyte-like cells.

scholarly journals The CXCL12 Crossroads in Cancer Stem Cells and Their Niche

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 469
Author(s):  
Juan Carlos López-Gil ◽  
Laura Martin-Hijano ◽  
Patrick C. Hermann ◽  
Bruno Sainz
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Tumor Microenvironment ◽  
Cancer Stem Cells ◽  
Crucial Role ◽  
Diverse Group ◽  
Hematopoietic Stem ◽  
Stem Cell Support ◽  
Cell Support ◽  
Tumor Entities

Cancer stem cells (CSCs) are defined as a subpopulation of “stem”-like cells within the tumor with unique characteristics that allow them to maintain tumor growth, escape standard anti-tumor therapies and drive subsequent repopulation of the tumor. This is the result of their intrinsic “stem”-like features and the strong driving influence of the CSC niche, a subcompartment within the tumor microenvironment that includes a diverse group of cells focused on maintaining and supporting the CSC. CXCL12 is a chemokine that plays a crucial role in hematopoietic stem cell support and has been extensively reported to be involved in several cancer-related processes. In this review, we will provide the latest evidence about the interactions between CSC niche-derived CXCL12 and its receptors—CXCR4 and CXCR7—present on CSC populations across different tumor entities. The interactions facilitated by CXCL12/CXCR4/CXCR7 axes seem to be strongly linked to CSC “stem”-like features, tumor progression, and metastasis promotion. Altogether, this suggests a role for CXCL12 and its receptors in the maintenance of CSCs and the components of their niche. Moreover, we will also provide an update of the therapeutic options being currently tested to disrupt the CXCL12 axes in order to target, directly or indirectly, the CSC subpopulation.

scholarly journals Exploration of Alternative Splicing Events in Mesenchymal Stem Cells from Human Induced Pluripotent Stem Cells

Genes ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 737
Author(s):  
Ji-Eun Jeong ◽  
Binna Seol ◽  
Han-Seop Kim ◽  
Jae-Yun Kim ◽  
Yee-Sook Cho
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Alternative Splicing ◽  
Functional Enrichment ◽  
Actin Binding ◽  
Pcr Analysis ◽  
Valuable Insight ◽  
Sequencing Analysis ◽  
Induced Pluripotent ◽  
Insight Into

Although comparative genome-wide transcriptomic analysis has provided insight into the biology of human induced pluripotent stem cell-derived mesenchymal stem cells (iMSCs), the distinct alternative splicing (AS) signatures of iMSCs remain elusive. Here, we performed Illumina RNA sequencing analysis to characterize AS events in iMSCs compared with tissue-derived MSCs. A total of 4586 differentially expressed genes (|FC| > 2) were identified between iMSCs and umbilical cord blood-derived MSCs (UCB-MSCs), including 2169 upregulated and 2417 downregulated genes. Of these, 164 differentially spliced events (BF > 20) in 112 genes were identified between iMSCs and UCB-MSCs. The predominant type of AS found in iMSCs was skipped exons (43.3%), followed by retained introns (19.5%), alternative 3′ (15.2%) and 5′ (12.8%) splice sites, and mutually exclusive exons (9.1%). Functional enrichment analysis showed that the differentially spliced genes (|FC| > 2 and BF > 20) were mainly enriched in functions associated with focal adhesion, extracellular exosomes, extracellular matrix organization, cell adhesion, and actin binding. Splice isoforms of selected genes including TRPT1, CNN2, and AP1G2, identified in sashimi plots, were further validated by RT-PCR analysis. This study provides valuable insight into the biology of iMSCs and the translation of mechanistic understanding of iMSCs into therapeutic applications.

scholarly journals Hampering Stromal Cells in the Tumor Microenvironment as a Therapeutic Strategy to Destem Cancer Stem Cells

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3191
Author(s):  
Katherine Po Sin Chung ◽  
Rainbow Wing Hei Leung ◽  
Terence Kin Wah Lee
Keyword(s):  
Stem Cells ◽  
Tumor Microenvironment ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Stromal Cells ◽  
Current Knowledge ◽  
Special Focus ◽  
Intrinsic Regulation ◽  
Mechanistic Basis ◽  
Novel Therapeutic Strategies

Cancer stem cells (CSCs) within the tumor bulk play crucial roles in tumor initiation, recurrence and therapeutic resistance. In addition to intrinsic regulation, a growing body of evidence suggests that the phenotypes of CSCs are also regulated extrinsically by stromal cells in the tumor microenvironment (TME). Here, we discuss the current knowledge of the interplay between stromal cells and cancer cells with a special focus on how stromal cells drive the stemness of cancer cells and immune evasive mechanisms of CSCs. Knowledge gained from the interaction between CSCs and stromal cells will provide a mechanistic basis for the development of novel therapeutic strategies for the treatment of cancers.

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