Indiana University

Pharmastem Therapeutics, Inc.

Genzyme Corporation

Research Corporation Technologies, Inc.

Biocyte Corporation

University of Texas System

Sloan-kettering Institute for Cancer Research

Advanced Research & Technology Institute

Anormed, Inc.

Advanced Research and Technologyinc

Genzyme Global S.à.r.l.

Hal E Broxmeyer

Edward A Boyse

Gordon W Douglas

Gary James Bridger

Michael J Abrams

Geoffrey W Henson

Ronald Trevor MacFarland

Gary B Calandra

David C Dale

Scott Cooper

Patrick S Gentile

Charlie R Mantel

Charles Mantel

Li Lu

Byoung S Kwon

Andreas H Sarris

Darron R Brown

Robert Hromas

Kenneth H Fife

Michell D Krathwohl

Maegan Lynn Capitano

Qingchun Cai

Jeff V Ravetch

Ronald Trevor Macfarland

C David Dale

Dale C David David

Various aspects and embodiments disclosed herein relate generally to the modelling, treatment, reducing resistance to the treatment, prevention, and diagnosis of a condition/disease associated with insufficient quantity and/or quality of hematopoietic stem cells (HSCs) and differentiated blood cells thereof. Embodiments include compositions and methods for treating the condition/disease, comprising the step of providing to a subject at least one therapeutically effective dose of a composition disclosed herein. Other embodiments include methods for generating and/or collecting hematopoietic stem cells from a subject.

Compositions and methods for treating a clinical condition through the use of hematopoietic stem cells

Methods to elevate progenitor and stem cell counts in animal subjects using compounds which bind to the chemokine receptor CXCR4 are disclosed. Preferred embodiments of such compounds are of the formulaZ-linker-Z'&#x2003;&#x2003;(1) 

Methods to mobilize progenitor/stem cells

Certain nitrogen-containing compounds that bind the chemokine receptor CXCR4 are able to mobilize progenitor and/or stem cells into the peripheral blood to permit harvesting them for stem cell transplantation.

The present invention relates to hematopoietic stem and progenitor cells of neonatal or fetal blood that are cryopreserved, and the therapeutic uses of such stem and progenitor cells upon thawing. In particular, the present invention relates to the therapeutic use of fetal or neonatal stem cells for hematopoietic (or immune) reconstitution. Hematopoietic reconstitution with the cells of the invention can be valuable in the treatment or prevention of various diseases and disorders such as anemias, malignancies, autoimmune disorders, and various immune dysfunctions and deficiencies. In another embodiment, fetal or neonatal hematopoietic stem and progenitor cells which contain a heterologous gene sequence can be used for hematopoietic reconstitution in gene therapy. In a preferred embodiment of the invention, neonatal or fetal blood cells that have been cryopreserved and thawed can be used for autologous (self) reconstitution.

Isolation and preservation of fetal and neonatal hematopoietic stem and progenitor cells of the blood

Full length cDNAs, L2G25B and 4-1BB, were isolated and sequenced. The cDNA L2G25B encodes for the lymphokine, macrophage inflammatory protein-1&agr; or MIP-1&agr;. The studies disclosed herein suggest that MIP-1&agr; and MIP-&bgr; can, through rapid action, modulate early myeloid progenitor cell proliferation. Recombinant proteins have been produced for the cytokine, L2G25BP (Macrophage Inflammatory Protein-1&agr;, MIP-1&agr;). By employing the recombinant protein (rMIP-1&agr;), receptors for MIP-1&agr; were identified on Con A-stimulated and unstimulated CTLL-R8, a T-cell line, and LPS-stimulated RAW 264.7, a macrophage-cell line. Purified recombinant murine macrophage inflammatory protein-1 alpha (rmuMIP-&agr;), was assessed for effects on proliferation of granulocyte-macrophage (CFU-GM), erythroid (BFU-E), and multipotential (CFU-GEMM) progenitor cells. The results suggest that rmuMIP-1&agr; has myelosuppressive activity in vivo. The cDNA clone, called 4-1BB, is an inducible receptor-like sequence found in both cytolytic and helper T-cells.

Nucleic acid encoding MIP-1&agr; Lymphokine

The inventors have cloned and expressed the chemokine-like genes from MCV type 1 and the closely related MCV type 2 in order to determine a potential role for these proteins in the viral life cycle. These are the first viral chemokines that have been shown to antagonize the chemotactic activity of human chemokines and the first viral chemokines that have been shown to have inhibitory activity on human hematopoietic progenitor cells. Methods and compositions for exploiting these proteins are disclosed herein.

Functional characterization of the C-C chemokine-like molecules encoded by molluscum contagiosum virus types 1 and 2

Described are preferred processes and compositions for suppressing myeloid cells in mammals. Preferred processes and compositions involve the use of chemokines in synergistic combinations or while they are substantially completely in monomeric form (i.e. substantially free from their polymerized or aggregated forms).

Methods for suppressing myeloid cells with chemokines

Described are preferred processes for suppressing proliferation of or for myeloprotecting myeloid cells in mammals. The processes involve the use of chemokines of the group Macrophage Inflammatory Protein-2.alpha. (MIP-2.alpha.), Platelet Factor 4 (PF4), Interleukin-8 (IL-8) and Macrophage Chemotactic and Activating Factor (MCAF), or involve the use of these chemokines or Macrophage Inflammatory Protein-1.alpha. (MIP-1.alpha.) in synergistic combinations or while they are substantially completely in monomeric form (i.e. substantially free from their polymerized or aggregated forms).

Compositions of myeloid-cell-suppressive chemokines

The present invention discloses the correct processing of IP-10, a myelosuppressive protein produced by certain cells such as keratinocytes, monocytes and human endothelial cells upon stimulation by .gamma.-interferon. Also disclosed is a method of treating human cancer patients by applying IP-10 in a pharmaceutical composition in conjunction with certain antineoplastic agents.

Methods and compositions incorporating IP-10

The invention comprises a factor having the following characteristics:

Biologically active factor

The present invention relates to hematopoietic stem and progenitor cells of neonatal or fetal blood that are cryopreserved, and the therapeutic uses of such stem and progenitor cells upon thawing. In particular, the present invention relates to the therapeutic use of fetal or neonatal stem cells for hematopoietic (or immune) reconstitution. Hematopoietic reconstitution with the cells of the invention can be valuable in the treatment or prevention of various diseases and disorders such as anemias, malignancies, autoimmune disorders, and various immune dysfunctions and deficiencies. In another embodiment, fetal or neonatal hematopoietic stem and progenitor cells which contain a heterologous gene sequence can be used for hematopoietic reconstitution in gene therapy. In a preferred embodiment of he invention, neonatal or fetal blood cells that have been cryopreserved and thawed can be used for utologous (self) reconstitution.

Isolation and preservation of fetal and neonatal hematopoietic stem and

Method of inhibiting progenitor cell proliferation

Growing community of inventors

Indianapolis, IN, United States of America

Hal E Broxmeyer