The Ansary Stem Cell Institute (ASCI) brings together a premier team of scientists to focus on stem cells, which are primitive, unspecialized cells with the capacity to form all types of cells, tissues, and organs in the body. The Ansary Institute takes a collaborative approach to stem cell research by bringing together scientists from varied areas of biomedical research. The Institute was established in 2004 with a generous gift from Mr. Hushang Ansary. Since then, the Institute garnered approximately $26-million in external funding, including support from the Starr Foundation Tri-Institutional Stem Cell Initiative and the Empire State Stem Cell Board (NYSTEM). Ansary Institute researchers have made groundbreaking discoveries that show significant promise for the future of regenerative medicine (marshalling the body’s own resources to restore itself), the treatment of cardiovascular disease, and more. Recent notable Ansary Institute discoveries include clear steps toward the eventual clinical applicability of stem cells: identifying cells in adult mouse testes that can be converted to stem cells that in turn generate cardiac, vascular, and neuronal cell types; the unlimited expansion of blood-producing stem cell cultures, whereas previous best efforts would result in a colony of stem cells dying after a few days; and the unlimited generation of endothelial cells (the basic building blocks of the circulatory system) from human embryonic stem cells.  The Ansary Institute intends to lead the way in stem cell science to relieve human suffering.

Regulation of hematopoiesis by microvascular endothelium 

The hematopoietic microenvironment is critical for the self-renewal, proliferation, and differentiation of pluripotent hematopoietic stem cells. Within the hematopoietic microenvironment, whether it is embryonic yolk sac, fetal liver, or adult bone marrow, microvascular endothelium not only acts as a gatekeeper controlling the trafficking and homing of hematopoietic progenitors, but also provides cellular contact and secretes cytokines that allow for the preservation of the steady state hematopoiesis. We have developed a technique for the isolation and cultivation of adult bone marrow microvascular endothelium (BMEC) and fetal liver endothelial cells (FLEC). We have shown that BMEC and FLEC monolayers support the trafficking as well as long-term proliferation and terminal-differentiation of CD34 hematopoietic progenitors. Direct cellular contact between endothelial monolayers and progenitor cells enhances the survival and regeneration of pluripotent hematopoietic progenitor cells. Although we have shown that binding of CD34 progenitor cells to BMEC monolayers is partially mediated through interaction between CD34/L-selectin, b1, b2 integrins, and membrane-bound kit-ligand/c-kit receptor ligand pairs, as yet unrecognized membrane-bound adhesion molecule/chemoines are responsible for the self-renewal and homing of the pluripotent stem cells.

The major focus of our laboratory is to isolate and characterize known and novel adhesion and membrane-bound cytokines expressed by endothelium that regulate proliferation and adhesion of hematopoietic stem cells and their progenitors. To this end, we have utilized expression cloning strategy using BMEC and FLEC cDNA libraries to screen for known and novel adhesion/homing receptor and membrane-bound cytokines that regulate proliferation of hematopoietic progenitors. In collaboration with Dr. R. Crystal, adenoviral vectors overexpressing cytokines, and adhesion molecules are being used to examine their function in long-term CD34 progenitor-endothelial coculture studies. Direct introduction of adenoviral vectors expressing stem cell active cytokines, into hematopoietic microenvironment provides novel approaches for the treatment of acquired or congenital hematological disorders.

Neo-angiogenic and stromal profiling of Cancer tissue

Based on the hypothesis that autocrine and paracrine VEGF-A and VEGF-receptor signaling support proliferation and tissue invasive potential of subsets of breast cancer cells, breast cancer activation and proliferation of VEGFR2 and VEGFR3 endothelial cells results in the release of paracrine factors that supports in turn the growth of breast cancer cells. This is based on our previous demonstration that functional VEGF-receptors including VEGFR1, are expressed on subsets of breast cancer cells generating an autocrine loop that is essential for the survival, and progression of subsets of breast cancer cells. Therefore, inhibition of VEGFR/VEGF-A autocrine and paracrine pathways may be effective in inducing apoptosis of proliferating endothelial cells as well as in inhibiting the growth of breast cancer cells.Emerging evidence also suggests that VEGFR1 may also be expressed on the breast cancer SUPPORTIVE tissue. Therefore, targeting the breast cancer stromal tissues may provide a novel means to enhance anti-angiogenic and anti-tumor effect of chemotherapy.