BACKGROUND AND OBJECTIVES: There are a number of unique processes seen in the developing fetus that cease post-partum including that tumors rarely form, and scar-less wound healing and digit regeneration occur. In addition, cancer lines have been "reprogrammed" by co-culture with embryonic extracellular matrix (ECM). METHODS AND RESULTS: We have developed a naturally secreted human ECM (hECM) with embryonic-like characteristics which is secreted by neonatal fibroblasts grown in microcarrier suspension cultures under hypoxia. This upregulates a number of substances associated with stem cell niches in the body including various laminins, Collagen 4, CXCL12, NID1, NID2, and NOTCH2. hECM has been shown to support proliferation of hESCs and MSCs and diminish or eliminate tumor load in melanoma (B16), adenocarcinoma (MDA-MB-435), colon cancer (HT29) and glioma (C6) in both in vitro and in vivo animal studies. In the tumor chorioallantoic membrane (tumcam) model hECM significantly inhibited tumor growth and in subcutaneous mouse xenograft experiments, tumor growth was inhibited from 70∼90%. Co-cultures of fibroblasts and mesothelioma show support of fibroblast expansion with a concurrent inhibition of mesothelioma. The inhibitory affect is selective for cancer cells and cancer stem cells through the upregulation of Caspase 9 which forces the cells into apoptosis. CONCLUSIONS: These data show that hECM has the potential to show benefit in the treatment of various cancers as a coating for biopsy needle, tissue filler post tumor removal, and as an injectable into the tumor site.
BACKGROUND AND OBJECTIVES: There are a number of unique processes seen in the developing fetus that cease post-partum including that tumors rarely form, and scar-less wound healing and digit regeneration occur. In addition, cancer lines have been "reprogrammed" by co-culture with embryonic extracellular matrix (ECM). METHODS AND RESULTS: We have developed a naturally secreted humanECM (hECM) with embryonic-like characteristics which is secreted by neonatal fibroblasts grown in microcarrier suspension cultures under hypoxia. This upregulates a number of substances associated with stem cell niches in the body including various laminins, Collagen 4, CXCL12, NID1, NID2, and NOTCH2. hECM has been shown to support proliferation of hESCs and MSCs and diminish or eliminate tumor load in melanoma (B16), adenocarcinoma (MDA-MB-435), colon cancer (HT29) and glioma (C6) in both in vitro and in vivo animal studies. In the tumor chorioallantoic membrane (tumcam) model hECM significantly inhibited tumor growth and in subcutaneous mouse xenograft experiments, tumor growth was inhibited from 70∼90%. Co-cultures of fibroblasts and mesothelioma show support of fibroblast expansion with a concurrent inhibition of mesothelioma. The inhibitory affect is selective for cancer cells and cancer stem cells through the upregulation of Caspase 9 which forces the cells into apoptosis. CONCLUSIONS: These data show that hECM has the potential to show benefit in the treatment of various cancers as a coating for biopsy needle, tissue filler post tumor removal, and as an injectable into the tumor site.
Authors: Nimet Maherali; Rupa Sridharan; Wei Xie; Jochen Utikal; Sarah Eminli; Katrin Arnold; Matthias Stadtfeld; Robin Yachechko; Jason Tchieu; Rudolf Jaenisch; Kathrin Plath; Konrad Hochedlinger Journal: Cell Stem Cell Date: 2007-06-07 Impact factor: 24.633
Authors: Paul M Kulesa; Jennifer C Kasemeier-Kulesa; Jessica M Teddy; Naira V Margaryan; Elisabeth A Seftor; Richard E B Seftor; Mary J C Hendrix Journal: Proc Natl Acad Sci U S A Date: 2006-02-27 Impact factor: 11.205
Authors: Raymond L Page; Sakthikumar Ambady; William F Holmes; Lucy Vilner; Denis Kole; Olga Kashpur; Victoria Huntress; Ina Vojtic; Holly Whitton; Tanja Dominko Journal: Cloning Stem Cells Date: 2009-09
Authors: Kelly L Covello; James Kehler; Hongwei Yu; John D Gordan; Andrew M Arsham; Cheng-Jun Hu; Patricia A Labosky; M Celeste Simon; Brian Keith Journal: Genes Dev Date: 2006-03-01 Impact factor: 11.361