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Cornell Research Foundation Inc.

Sloan-kettering Institute for Cancer Research

Imclone System Incorporated

Larry Witte

Ihor R Lemischka

Shahin Rafii

Malcolm A S Moore

Bronislaw Pytowski

Kateri Moore

The invention is directed to a purified population of mammalian endothelial, muscle, or neural stem cells. The invention further provides methods for isolating such populations of cells; methods for using such populations of cells for treating mammals; methods for making vectors for gene therapy; and methods for carrying out gene therapy with such vectors.

Purified populations of stem cells

Primitive hematopoietic stem cells are closely associated with discrete in vivo microenvironments. These &ldquo;niches&rdquo; are thought to provide the molecular signals that mediate stem cell differentiation and self renewal. We have dissected the fetal liver microenvironment into distinct cellular components by establishing an extensive panel of stromal cell lines. One particular cell line maintains repopulating stem cells for prolonged in vitro culture periods. A subtraction cloning strategy has yielded a cDNA which encodes a cell surface glycoprotein with a restricted pattern of expression among stromal cell lines. This molecule, previously identified as dlk/Pref-1, contains EGF-like repeats which are related to those in the Notch/Delta/Serrate family of proteins. We have investigated the potential role of this molecule in hematopoietic stem/progenitor cell regulation. We show that the dlk protein displays activity on purified stem cells by promoting the formation of &ldquo;cobblestone areas&rdquo; of proliferation. These cobblestone areas contain both primitive high-proliferative potential progenitors as well as in vivo repopulating stem cells.

Use of delta-like protein to inhibit the differentiation of stem cells

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Stormville, NY, United States of America

Larry Witte