University of Pittsburgh

University of Louisville Research Foundation, Inc.

Allegheny University of the Health Sciences

Chimeric Therapies, Inc.

Suzanne T Ildstad

Mary Jane Elliott

Christina Kaufman

Camillo D Ricordi

Olav B Bergheim

Richard L Simmons

Yolanda Colson

Sherry M Wren

The present disclosure relates to human facilitating cells (hFC), and methods of isolating, characterizing, and using such hFCs.

Human facilitating cells

Methods of expanding FCs or stem cells are provided herein, as are methods of screening for compounds that increase expression of DOCK2 or decrease expression of Arhgap18, either of which improves engraftment.

Methods and compositions for expanding cells and improving engraftment

The invention provides for methods of screening for compounds that increase the expression of P-selectin, SDF-1, and/or CXCR4 on facilitatory cells (FCs). The invention also provides for methods of screening for compounds that increase the level of p-predendritic cells (p-pre DC) without substantially decreasing the level of natural killer (NK) cells in a population of FCs. The invention further provides for methods of characterizing the facilitating capability of FCs by evaluating such cells for the amount of P-selectin, SDF-1, and/or CXCR4.

Methods of screening for compounds that improve engraftment

The present invention relates to non-lethal methods of conditioning a recipient for bone marrow transplantation. In particular, it relates to the use of nonlethal doses of total body irradiation, total lymphoid irradiation, cell type-specific or cell marker-specific antibodies, especially antibodies directed to bone marrow stromal cell markers, NK cells, or the CD8 cell marker, cytotoxic drugs, or a combination thereof. The methods of the invention have a wide range of applications, including, but not limited to, the conditioning of an individual for hematopoietic reconstitution by bone marrow transplantation for the treatment of hematologic malignancies, hematologic disorders, autoimmunity, infectious diseases such as acquired immunodeficiency syndrome, and the engraftment of bone marrow cells to induce tolerance for solid organ, tissue and cellular transplantation.

Non-lethal methods for conditioning a recipient for bone marrow transplantation

The present invention relates to the use of a non-lethal preparative regimen for the treatment of a patient with human immunodeficiency virus (HIV) disease. In a clinical trial, an HIV-positive patient was conditioned by non-lethal doses of irradiation and a chemotherapeutic drug prior to receiving donor bone marrow cells from a baboon. While long-term engraftment of donor cells was not observed, the non-lethal preparative conditioning regimen was able to reduce the viral burden and improved the clinical outcome. Such method is useful for treatment of patients with advanced acquired immunodeficiency syndrome (AIDS).

Non-lethal conditioning methods for the treatment of acquired

The present invention relates to monoclonal antibodies (MAb) to hematopoietic facilitatory cells (FC). In particular, it relates to MAb against antigens expressed by murine FC, methods of generating the antibodies, and methods of using the same. MAb directed to markers that are expressed specifically or at higher levels by FC than by most other bone marrow cells have a wide range of applications, including but not limited to, rapid isolation of FC, identification of FC in a donor cell preparation, and molecular cloning of the genes encoding the corresponding target antigens.

Monoclonal antibodies to antigens expressed by hematopoietic

The present invention relates to non-lethal methods of conditioning a recipient for bone marrow transplantation. In particular, it relates to the use of nonlethal doses of total body irradiation, total lymphoid irradiation cell type-specific antibodies, especially antibodies directed to bone marrow stromal cell markers, cytotoxic drugs, or a combination thereof. The methods of the invention have a wide range of applications, including, but not limited to, the conditioning of an individual for hematopoietic reconstitution by bone marrow transplantation for the treatment of hematologic malignancies, hematologic disorders, autoimmunity, infectious diseases such as acquired immunodeficiency syndrome, and the engraftment of bone marrow cells to induce tolerance for solid organ, tissue and cellular transplantation.

Non-lethal methods for conditioning a recipient for bone marrow

The present invention relates to mammalian hematopoietic facilitatory cells (FC). In particular, it relates to the isolation, characterization and uses of the FC. The FC of the present invention can be distinguished from all other known bone marrow cells by their morphology, cell surface phenotype and in vivo function. It has now been established that purified hematopoietic stem cells alone or bone marrow cells depleted of FC do not readily engraft in a recipient. When co-administered with other bone marrow cells, especially the hematopoietic stem cells into a recipient, the FC enhance their engraftment, without apparent adverse biologic activities. In fact, the ability of the FC to enhance the engraftment of bone marrow cells in esablishing lymphohematopoietic chimerism without producing graft versus host disease also induces donor-specific tolerance to permit the permanent acceptance of donor's cells, tissues and organs. Therefore, FC may have a wide range of applications, including, but not limited to, hematopoietic reconstitution by bone marrow transplantation for the treatment of cancers, anemias, autoimmunity, immunodeficiency, viral infections and metabolic disorders as well as facilitation of solid organ, tissue and cellular transplantation.

Hematopoietic facilitatory cells and their uses

The present invention relates to non-lethal methods of conditioning a recipient for bone marrow transplantation. In particular, it relates to the use of sublethal doses of total body irradiation, cell type-specific antibodies, especially antibodies directed to bone marrow stromal cell markers, cytotoxic drugs, or a combination thereof. The methods of the invention have a wide range of applications, including, but not limited to, the conditioning of an individual for hematopoietic reconstitution by bone marrow transplantation for the treatment of hematologic malignancies, hematologic disorders, autoimmunity, infectious diseases such as acquired immunodeficiency syndrome, and the engraftment of bone marrow cells to induce tolerance for solid organ, tissue and cellular transplantation.

Growing community of inventors

Pittsburgh, PA, United States of America

Suzanne T Ildstad