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"Cancer Stem Cell" Production and Sales

Proposing a Time Machine Approach to Cancer Treatment

Cancer treatment aims to cure cancer by using various methods such as surgery, drug therapy, and radiation therapy. However, it is becoming increasingly known that even if most of the cancerous tissue is removed, if even a small amount of cells called "cancer stem cells" remain in the body, the cancer will recur. Although cancer stem cells have not attracted much attention as a therapeutic target due to their rarity in cancer tissues, we will contribute to the development of innovative cancer therapies that can be individually tailored by creating cancer stem cells (cCSCs) using our unique technology to enable prevention and prediction of cancer incidence and to reflect this in medical treatment.



Order information

①Interveiw

We will consult with you in advance about the form of provision of "cancer stem cells" and the period of preparation according to your requirements.


②Create cancer stem cells

After the contract is signed, we will start to create cCSCs. Delivery time depends on the details of the contract.

③Utilization of cCSCs

We provide safe and highly reliable cancer stem cells generated by our proprietary technology.

We also offer the option of drug screening using the cCSCs and the search for molecules that could be targets for drug delivery systems.


Making a transaction

Please contact us using the contact form on the right.



A New Approach to Cancer Treatment

About Stem Cells

The human body is made up of 60 trillion cells, which are produced from special cells called "stem cells".

Stem cells have two important properties: the ability to divide and produce their own identical cells (self-renewal) and the ability to differentiate into various types of cells (pluripotency). The name "stem cell" comes from the fact that they are like the stem of a cell.

Induced pluripotent stem cells (iPS cells), the result of Nobel Prize-winning research, are a representative example of stem cells that can be applied to this technology.

"Cancer stem cells" and their research

Cancer is one of the most frightening diseases we face, but even in cancer, there are cells that correspond to "stem cells". These are called "cancer stem cells".

In addition to the properties of stem cells, cancer stem cells have the ability to form tumors (tumorigenicity).

Cancer stem cells produce tumors and are thought to play a major role in cancer metastasis and recurrence. For this reason, cancer stem cells are attracting attention as a new target for cancer therapy, but it has been reported that they are resistant to drugs and radiation, and conventional therapy does not produce the desired effect.

In addition, "cancer stem cells" exist in less than 10% of all cells that make up cancer, making it difficult to apply them directly to research and the development of new drugs.

Creating cancer stem cells using a new method

This led to the idea of creating cancer stem cells from normal stem cells. Rather than extracting cancer stem cells from cancerous tissues, cancer stem cells are created by preparing an environment in which normal stem cells can be transformed into cancer stem cells.

By focusing our research on their "environment," we have discovered the environment that turns iPS cells into cancer stem cells. This discovery has made it possible to create cancer stem cells in a stable manner.

We are the only company in the world that is able to prepare and provide cancer stem cells using this method.



Cancer stem cell model "cCS cell"

What is a "cancer-inducing environment"?

To obtain cancer stem cells, we culture normal stem cells with the culture supernatant of a cancer cell line. This culture supernatant becomes the "cancer-inducing environment.

So, how can this culture supernatant be a "cancer-inducing environment"? This is because so-called "cancer cell lines" regularly secrete a variety of factors, such as growth factors, differentiation factors, and inflammation-related factors, which are only produced in emergency situations in normal tissue cells. We believe that these factors in the culture supernatant of cancer cell lines can continuously stimulate stem cells to emerge, and we have reported many research results in academic papers.

This method, which uses a cancer-inducing environment, does not involve the introduction of specific genes or the intentional mutation of genes, making it a valuable method for studying naturally occurring carcinogenesis. We have named the cancer stem cells generated by this method as created cancer stem cells (cCS cells).

Application of cCS cells

Application to drug screening

It is possible to obtain various types of tissue cancer stem cells by regulating the environment in which cancer is created and by further inducing differentiation of cCS cells. These cells can be used as targets for the screening of existing and new anticancer drugs. Although cancer stem cells are said to be resistant to anticancer drugs, studies have shown that some, but not all, cancer stem cells are sensitive to these drugs. However, since sensitivity varies from cell to cell, it is necessary and possible to screen the cCS cells that we create.

Application to custom-made cancer treatment

When used alone, anticancer drugs are effective only 30-40% of the time. There are many drugs that have a response rate of 10% or 20%, so the possibility of them not working is much greater. If an anticancer drug is ineffective, it does not serve as a cure, but rather as a "poison" that causes the patient to suffer.

By generating cCSC cells from your own cells while you are healthy and establishing effective treatment methods in advance in preparation for the next stage of the disease, you can contribute to improving the survival rate when cancer occurs and eventually reduce the recurrence rate.



Patents

  • Application Number 2013-082671(Kokai number 2015-082409, Kokai number 2016-546537, Kokai number 2017-034004)
  • Application Number 2015-082409(Kokai number 2016-106617)
  • Application Number 2016-546537(Kokai number 2017-086091)
  • Application Number 2019-081551
  • Application Number 2019-091590

Alliance Partners

Co-investigators

Japan

Academic Field of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University

  • Yoshiaki Iwasaki
  • Toshiaki Ohara
  • Hiroki Kakuta

Seno Laboratory, Academic Field of Interdisciplinary Science and Engineering in Health Systems, Okayama University

  • Maram Zacky Zahra
  • Kazuki Kumon

Tokyo Medical University

  • Marta Prieto Vira

Fujita Health University

  • Tadahiro Nagaoka

Tokyo University of Science

  • Tsukasa Shigehiro

Junshin Gakuen University

  • Yu Sugii
outside of Japan
  • Chen Ling, MD, PhD (Tianjin, China)
  • Li Fu, MD, PhD (Tianjin, China)
  • Xiaoin Hu, MD, PhD (Tianjin, China)
  • Aung Ko Ko Oo, PhD (Yangon, Myammer)
  • Md Jahangir Alam, PhD (Bangradish)
  • David S Salomon (NCI, USA)
  • Mary JC Hendrix (Northwestern Univ, USA)

Evidence

Hypothesis of cancer stem cells (1860-1870)

The existence of cancer stem cells has been predicted since the late 19th century, over 100 years ago.

  • Durante F. Nesso fisio-pathologico tra la struttura dei nei materni e la genesi di alcuni tumori maligni. Arch Memor Observ Chir Pract 1874;11:217-26.
  • Cohnheim J. Ueber entzundung und eiterung. Path Anat Physiol Klin Med 1867;40:1-79.
  • Cohnheim J. Congenitales, quergestreiftes Muskelsarkon der Nireren. Virchows Arch 1875;65:64.

Discovery of Cancer Stem Cells

More than 100 years after the hypothesis, it was first confirmed as a cancer condition until the end of the 20th century.

  • Bonnet, D; Dick, JE.. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat. Med. 1997;3(7):730-737.

Creating Cancer Stem Cells from iPS Cells

In the 21st century, for the first time in the world, cancer stem cells have been successfully created from iPS cells under naturally occurring conditions.

  • Chen L,Kasai T,Li,Y,Sugii Y,Jin G,Okada M,Vaidyanath A,Mizutani A,Satoh A,Kudoh T,Hendrix MJ,Salomon DS, Fu L,Seno M. A model of cancer stem cells derived from mouse induced pluripotent stem cells. PLoS One.2012;7(4):e33544.

Published papers

2021
  • Kumon, K., et al. Differentiation of cancer stem cells into erythroblasts in the presence of CoCl2. Sci Rep 2021; 11;23977.
  • Ghmkin H., et al. Chapter 15, Availability of Pluripotent Stem Cells from Normal Cells in Cancer Science. In “Stem Cells Latest Advances, Ed. Khawaja H. Haider”, 2021, Springer e-book, ISBN: 978-3-030-77052-5
  • Ghmkin H., et al. MEK1/2 is a bottleneck that induces cancer stem cells to activate the PI3K/AKT pathway, Biochem Biophys Res Commun, 2021; 583; 49-55.
  • Sheta M, et al. Chronic exposure to FGF2 converts iPSCs into cancer stem cells with an enhanced integrin/focal adhesion/PI3K/AKT axis. Cancer Lett. 2021;521:142-154.
  • Zahra MH, et al. Metformin suppresses self-renewal and stemness of cancer stem cell models derived from pluripotent stem cells. Cell Biochem Funct. 2021;39(7):896-907.
  • Abu Quora HA, et al. Microenvironment of mammary fat pads affected the characteristics of the tumors derived from the induced cancer stem cells. Am J Cancer Res. 2021;11(7):3475-3495.
  • Ishii, H., et al. Cripto-1 as a Potential Target of Cancer Stem Cells for Immunotherapy. Cancers (Basel) 2021; 13(10): 2491.
  • Nawara HM, et al. Paclitaxel-Based Chemotherapy Targeting Cancer Stem Cells from Mono- to Combination Therapy. Biomedicines. 2021;9(5):500.
  • Afify SM, et al. How can we turn the PI3K/AKT/mTOR pathway down? Insights into inhibition and treatment of cancer. Expert Rev Anticancer Ther. 2021;21(6):605-619.
  • Afify SM, et al. Cancer Stem Cell Initiation by Tumor-Derived Extracellular Vesicles. Methods Mol Biol. 2021. doi: 10.1007/7651_2021_371. 
  • Ishii, H., et al. A Novel Artificially Humanized AntiCripto-1 Antibody Suppressing Cancer Cell Growth. Int. J. Mol. Sci. 2021; 22, 1709.
  • Ishii1, H., et al. Isolation and characterization of cancer stem cells derived from human glioblastoma, Am J Cancer Res 2021;11(2):441-457.
  • Ghmkin H., et al. Cancer Stem Cell Microenvironment Models with Biomaterial Scaffolds In Vitro. Processes 2021, 9, 45.
2020
  • Nawara HM, et al. An assay for cancer stem cell-induced angiogenesis on chick chorioallantoic membrane. Cell Biol Int. 2021;45(4):749-756.
  • Osman A, et al. Tumor-associated macrophages derived from cancer stem cells. Acta Histochem. 2020;122(8):151628.
  • Mansour H, Hassan G, Afify SM, Yan T, Seno A, Seno M. Metastasis Model of Cancer Stem Cell-Derived Tumors. Methods Protoc. 2020;3(3):E60.
  • Du J et al. Signaling Inhibitors Accelerate the Conversion of mouse iPS Cells into Cancer Stem Cells in Tumor Microenvironment. Sci Rep.2020,10,9955.
  • Nawara HM et al. Paclitaxel and Sorafenib: the effective combination of suppressing the self-renewal of cancer stem cells. Cancers (Basel).2020,12(6),1360.
  • Hassan G,Seno M, Blood and cancer: Blood and Cancer Stem Cells as Origin of Hematopoietic Cells in Solid Tumor Microenvironments.(Review). Cells 2020,9,1293.
  • Hassan G,Du J,Afify SM,Seno A,Seno M. Cancer stem cell generation by silenced MARK enhancing PI3K/AKT signaling. Med Hypotheses.2020;141:109742.
  • Osman A,Afify SM,Hassan G,Fu X,Seno A,Seno M. Revisiting Cancer Stem Cells as the Origin of Cancer-Associated Cells in the Tumor Microenvironment:A Hypothetical View from the Potential of iPSCs. Cancers(Basal).2020;12(4).pii:E879.
  • Afify SM et al. A novel model of liver cancer stem cells developed from induced pluripotent stem cells. Br J Cancer.2020;122(9):1378-1390.
  • Du J etbal. Upregulated Ccl20 and Ccr6 in cancer stem cells converted from mouse iPS cells. J Res Med Dent Sci.2020;8(1):200-207.
2019
  • Hassan G et al. Hematopoietic Cells Derived from Cancer Stem Cells Derived from Cancer Stem Cells Generated from Mouse Induced Pluripotent Stem Cells. Cancer(Basel).2019 Dec 29;12(1).pii:E82
  • Seno A et al. Cancer stem cell induction from mouse embryonic stem cells. Oncol Lett.2019 Sep;18(3):2756-2762.
  • Afify SM et al. Metastasis of Cancer Stem Cells Developed in the Micrornvironment of Hepatocellular Carcinoma. Bioengineering(Basel).2019;6(3).pii:E73.
  • Afify SM et al. Method to Convert Stem Cells into Cancer Stem Cells. Methods Protoc.2019;2(3).pii:E71.
  • Seno A et al. Daunorubicin can eliminate iPS-derived Cancer Stem Cells via ICAD/CAD-Independent DNA Fragmentation. Cancer Drug Resist 2019;2:335-350.
  • Afify SM,Seno M. Conversion of Stem Cells to Cancer Stem Cells: Undercurrent of Cancer Initation.(Rrview)Cancers(Basel).2019;11(3).pii:E345.
  • Khayrai AC et al. Trageting Ovarian Cancer Cells Overexpressing CD44 with Immnoliposomes Encapsulating Glycosylated Paclitaxel.Int J Mol Sci.2019;20(5).pii:E1042.
  • Katsura Y et al. A Novel Combination Cancer Therapy with Iron Chelator Trageting Cancer Stem Cells(Basel).2019;11(2).pii:E177.
2018
  • Alam MJ et al. Exogenous Cripto-1 Suppresses Self-Renewal of Cancer Stem Cell Model. Int J Mol Sci.2018 Oct 26;19(11).pii:E3345.
  • Seno A,Seno M. Commonly expressed genes among cancer stem cells induced from hiPSCs and Obtaioned from cancer tissues or cell Lines. Tumor and Microenvironment,2018;1(2):45-54.
  • Oo AKK et al. Up-Regulation of PI 3-Kinases and the Activation of PI3K-Akt Signaling Pathway in Cancer Stem-Like Cells Through DNA Hypomethylation Mediated by the Cancer Microenvironment. Transl Oncol.2018;11(3):653-663.
  • Mahmud H et al. Targeting Glioblastoma Cells Expressing CD44 with Liposomes Encapsulating Doxorubicin and Displaying Chlorotoxin-IgG Fc Fusion Protein. Int J Mol Sci.2018 Feb 26;19(3).pii:E659.