Human embryonic stem cells secrete soluble factors that inhibit cancer cell growth

Giuffrida, Domenica; Rogers, Ian; Nagy, András; Calogero, Aldo E.; Brown, Theodore J.; Casper, Robert F.

doi:10.1111/j.1365-2184.2009.00640.x

Cited by 41 publications

(40 citation statements)

References 30 publications

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“…In their study, cancer cell proliferation decreases after exposure to human ES cell-conditioned media as compared to the controls containing mouse fibroblast conditioned media and normal cancer cell media. Dilution studies demonstrated that depletion of nutrients in human ES cell-conditioned medium does not contribute to the arrest of cancer cell proliferation [21]. This study confirms that hES cells secrete factors smaller than 10 kD which plays a major role in inhibiting cell proliferation and terminating the cell cycle.…”

Section: Embryonic Microenvironment and Cancersupporting

confidence: 63%

Bioengineering Embryonic Stem Cell Microenvironments for the Study of Breast Cancer

Raof

Mooney

Xie

2011

IJMS

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Breast cancer is the most prevalent disease amongst women worldwide and metastasis is the main cause of death due to breast cancer. Metastatic breast cancer cells and embryonic stem (ES) cells display similar characteristics. However, unlike metastatic breast cancer cells, ES cells are nonmalignant. Furthermore, embryonic microenvironments have the potential to convert metastatic breast cancer cells into a less invasive phenotype. The creation of in vitro embryonic microenvironments will enable better understanding of ES cell-breast cancer cell interactions, help elucidate tumorigenesis, and lead to the restriction of breast cancer metastasis. In this article, we will present the characteristics of breast cancer cells and ES cells as well as their microenvironments, importance of embryonic microenvironments in inhibiting tumorigenesis, convergence of tumorigenic and embryonic signaling pathways, and state of the art in bioengineering embryonic microenvironments for breast cancer research. Additionally, the potential application of bioengineered embryonic microenvironments for the prevention and treatment of invasive breast cancer will be discussed.

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Section: Embryonic Microenvironment and Cancersupporting

confidence: 63%

Bioengineering Embryonic Stem Cell Microenvironments for the Study of Breast Cancer

Raof

Mooney

Xie

2011

IJMS

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“…These effects were not seen when these cells were cultured in hESCs-conditioned medium (hESCs-CM) [15, 18, 19]. In contrast, other studies reported that the exposure of cancer cells to hESCs-CM inhibited their tumorigenicity due to reduced proliferation and increased apoptosis [20]. In the present study we sought to determine the origin of the factors involved in these antitumorigenic effects.…”

Section: Introductionmentioning

confidence: 95%

Reprogramming Malignant Cancer Cells toward a Benign Phenotype following Exposure to Human Embryonic Stem Cell Microenvironment

et al. 2017

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The embryonic microenvironment is well known to be non-permissive for tumor development because early developmental signals naturally suppress the expression of proto-oncogenes. In an analogous manner, mimicking an early embryonic environment during embryonic stem cell culture has been shown to suppress oncogenic phenotypes of cancer cells. Exosomes derived from human embryonic stem cells harbor substances that mirror the content of the cells of origin and have been reported to reprogram hematopoietic stem/progenitor cells via horizontal transfer of mRNA and proteins. However, the possibility that these embryonic stem cells-derived exosomes might be the main effectors of the anti-tumor effect mediated by the embryonic stem cells has not been explored yet. The present study aims to investigate whether exosomes derived from human embryonic stem cells can reprogram malignant cancer cells to a benign stage and reduce their tumorigenicity. We show that the embryonic stem cell-conditioned medium contains factors that inhibit cancer cell growth and tumorigenicity in vitro and in vivo. Moreover, we demonstrate that exosomes derived from human embryonic stem cells display anti-proliferation and pro-apoptotic effects, and decrease tumor size in a xenograft model. These exosomes are also able to transfer their cargo into target cancer cells, inducing a dose-dependent increase in SOX2, OCT4 and Nanog proteins, leading to a dose-dependent decrease of cancer cell growth and tumorigenicity. This study shows for the first time that human embryonic stem cell-derived exosomes play an important role in the tumor suppressive activity displayed by human embryonic stem cells.

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“…For examples, MSCs secreted various trophic factors to modulate the immune response and cell survival [107] . PSCs have also been shown to self-regulate the expansion and differentiation through autocrine/paracrine signaling such as Wnt, lefty, and Activin A [108][109][110][111][112] . For hematopoietic differentiation, the secreted VEGF, stem cell factor (SCF) and anti-apoptotic factors from ESCs stimulated the formation of colony-forming cells [113] .…”

Section: Outlet Portsmentioning

confidence: 99%

Engineering stem cell niches in bioreactors

Liu

Liu²,

Zang³

et al. 2013

WJSC

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Stem cells, including embryonic stem cells, induced pluripotent stem cells, mesenchymal stem cells and amniotic fluid stem cells have the potential to be expanded and differentiated into various cell types in the body. Efficient differentiation of stem cells with the desired tissue-specific function is critical for stem cell-based cell therapy, tissue engineering, drug discovery and disease modeling. Bioreactors provide a great platform to regulate the stem cell microenvironment, known as "niches", to impact stem cell fate decision. The niche factors include the regulatory factors such as oxygen, extracellular matrix (synthetic and decellularized), paracrine/ autocrine signaling and physical forces (i.e. , mechanical force, electrical force and flow shear). The use of novel bioreactors with precise control and recapitulation of niche factors through modulating reactor operation parameters can enable efficient stem cell expansion and differentiation. Recently, the development of microfluidic devices and microbioreactors also provides powerful tools to manipulate the stem cell microenvironment by adjusting flow rate and cytokine gradients. In general, bioreactor engineering can be used to better modulate stem cell niches critical for stem cell expansion, differentiation and applications as novel cell-based biomedicines. This paper reviews important factors that can be more precisely controlled in bioreactors and their effects on stem cell engineering.

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Human embryonic stem cells secrete soluble factors that inhibit cancer cell growth

Abstract: Our findings provide evidence that the human embryonic microenvironment contains soluble factor(s) that are capable of inhibiting growth of cancer cells, and that exposure to such factors may represent a new cancer treatment strategy.

Cited by 41 publications

References 30 publications

Bioengineering Embryonic Stem Cell Microenvironments for the Study of Breast Cancer

Bioengineering Embryonic Stem Cell Microenvironments for the Study of Breast Cancer

Reprogramming Malignant Cancer Cells toward a Benign Phenotype following Exposure to Human Embryonic Stem Cell Microenvironment

Engineering stem cell niches in bioreactors

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