SVIBOR - Project code: 3-01-004

MINISTRY OF SCIENCE AND TECHNOLOGY

Strossmayerov trg 4, HR - 10000 ZAGREB
tel.: +385 1 459 44 44, fax: +385 1 459 44 69
E-mail: ured@znanost.hr

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Project code: 3-01-004

New approaches to the improvement of bone marrow transplantation

Main researcher: MARUŠIĆ, MATKO (29254)

Assistants

Type of research: basic
Duration from: 01/01/91. to 12/31/93.

Papers on project (total): 11
Papers on project quoted in Current Contents: 6

Institution name: Medicinski fakultet, Zagreb (108)
Department/Institute: Department of Physiology
Address: Šalata 3
City: 10000 - Zagreb, Croatia

Communication: Phone: 385 (041 4566 913; Fax: 385 (0)1 4566 724

Summary: Three new approaches to the improvement of the results of bone marrow transplantation are planned. Mouse experimental model will be used. First assumption (based on own preliminary data) is that the treatment of bone marrow cells in vitro with combination of cyclosporin A and metotrexate would remove mature T cells which cause the GVHR. Second, it will be tested (the hypothesis) whether the mature T lymphocytes in the bone marrow transplant have a favorable influence on engraftment and function of the transplant by (a) secretion of lymphokines which stimulate bone marrow stem cells and (b) neutralization of a portion of reaction of the recipient against the graft, which spares the transplanted bone marrow stem cells. Third, it will be tested whether the addition of extracellular matrix, particularly laminin or agents which inhibit its binding to the cell receptor (antilaminin antibodies or inhibitory peptides), can influence the extent of homing and proliferation of stem cells from the graft. All experiments will be performed in symetrical and identical genetic combinations of bone marrow donors and recipients (syngeneic, allogeneic, semisyngeneic, semiallogeneic, minor). All effects will be estimates through information on recipient survival, dynamics of immunohematological recovery and the level of chimerism of lymphoid cells

Keywords: bone marrow transplantation, mice, T lymphocytes, cyclosporin A, hydrocortison, extracellular matrix, laminin, chimerism, GVHR, stem cells

Research goals: The aim of the project is to improve the results of bone marrow transplantation. Three approaches are tested. 1. Purging of the bone marrow T cells by in vitro treatment with cyclosporin A and hydrocortisone. The treatment should deplete T cell but will not affect the ability of bone marrow stem cells to form colonies in vitro and proliferate in vivo. A confirmation of the hypothesis (in vitro and in vivo) would provide a simple, cheap and efficacious method of T cell purging from the bone marrow. 2. Pretreatment of the T cells from the bone marrow transplant in such manner that they retain their antigenicity and ability to secrete lymphokines while loosing the potential to elicit graft-versus-host reaction (GVHR). 3. A systematic investigation of interactions of bone marrow stem cells with extracellular matrix to enhance the homing and proliferation of the stem cells. Bone marrow cells will be admixed with extracellular matrix components and/or phorbol-myristate-acetate (PMA) to affect the interactions. The effect(s) should be seen at the level of survival and immunohematologic recovery of lethally irradiated bone marrow recipients.

COOPERATION - INSTITUTIONS

Name of institution: KBC Zagreb, Interna klinika, Zavod za hematologiju
Type of institution: International organization
City: 10000 - Zagreb, Croatia

Other information about the project.


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Last update: 10/18/95
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