Hypoxia Induces Multipotency in Skin Cells, Proteins Produced Trigger Cancer Stem Cell Death
New findings to be presented at 5th Annual Stem Cells and Regenerative Medicine World Congress. Histogen scientists have demonstrated that under hypoxic conditions normal human newborn fibroblasts become multipotent cells and express key pluripotent stem cell markers.
San Diego, CA (PRWEB) January 24, 2011
Histogen, Inc., a regenerative medicine company developing solutions based on the products of newborn cells grown under embryonic conditions, will present new findings today at the 5th Annual Stem Cells and Regenerative Medicine World Congress.
Histogen scientists have demonstrated that, in both monolayer and suspension cultures under hypoxic conditions, normal human newborn fibroblasts become multipotent cells and express key pluripotent stem cell markers including Oct4, Sox2 and Nanog as well as a number of tissue and germ layer-specific stem cell markers, such as Brachyury, Gata4, alpha-fetoprotein, and Pax6. The stem-like cells induced in monolayer are seeded onto dextran beads and grown in a hypoxic suspension where they secrete a variety of soluble and insoluble molecules associated with stem cell niches in the body, as well as rapid tissue growth with scarless healing.
Unlike traditional fibroblast conditioned media, the media from hypoxia-induced multipotent cells contains no TGF beta, a protein associated with scar formation, no Wnt 5a and 5b that have been associated with cancer formation, and significantly increased levels of Wnt 7a and follistatin, both of which have been shown in a variety of studies to stimulate native stem cells to generate new tissue. In addition, various embryonic matrix proteins have been associated with the reversion of cancer cell phenotype , and follistatin is known to induce apoptosis in cancer cells.
“Embryonic development is characterized by stem cell activation, rapid cell growth, and a highly controlled micro environment to prevent the induction of malignancy,” said Dr. Jonathan Mansbridge, Chief Scientific Officer at Histogen. “We are pleased our research has revealed that mimicking the hypoxic fetal environment induces cells to become multipotent and secrete proteins that have been shown to stimulate stem cell growth and inhibit both cancer stem cells and rapidly dividing cancer cell growth.”
In a study by Pinney et al, cancer cell lines exposed to the matrix produced by the hypoxia-induced multipotent cells upregulated Caspase 9 and went into a controlled cell death, known as apoptosis. To date, the cancer lines that have been positively affected in vitro and in two animal models include breast cancer, glioma, melanoma, colon cancer, and mesothelioma. The inhibitory effect is selective for malignant cells only, with cell death induced in both rapidly dividing cancer cells and non-dividing cancer stem cells.
“It is exciting to see that this matrix produces controlled cell death in multiple human cancer cell lines, and that it also targets cancer stem cells,” said Dr. David Easter, Professor of Clinical Surgery at UCSD Medical Center. “Plus, areas filled with this matrix after breast cancer resection have shown no tumor recurrence in the animal model, but untreated animals nearly always regrow tumors. These results point towards a significant new strategy in the post-surgical treatment of solid tumors.”
“Hypoxic Culture Conditions Induce a Stem Cell-Like Phenotype in Human Dermal Fibroblasts” and “Human Embryonic-like ECM (hECM) Stimulates Proliferation and Differentiation in Stem Cells While Killing Cancer Cells” will be presented by Dr. Michael Zimber, and Emmett Pinney respectively, during the Stem Cell Congress taking place January 24-25, 2011 in San Diego. Extracellular matrix compositions produced under the hypoxic conditions discussed here are covered by pending US patents 2010/0047305 and 2010/0124573.
Histogen, launched in 2007, seeks to redefine regenerative medicine by developing a series of high value products that do not contain embryonic stem cells or animal components. Through Histogen’s proprietary bioreactors that mimic the embryonic environment, newborn cells are encouraged to naturally produce the vital proteins and growth factors from which the Company has developed its rich product portfolio. Histogen has two product families ““ a proprietary liquid complex of embryonic-like proteins and growth factors, and a human Extracellular Matrix (ECM) material, ExCeltrix. For more information, please visit http://www.histogen.com.
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