Effect of nicotine on bone marrow cells

Institution:	La Jolla Institute for Molecular Medicine
Investigator(s):	Sophia Khaldoyanidi, M.D., Ph.D.
Award Cycle:	2001 (Cycle 10)	Grant #: 10KT-0036H	Award: $520,381
Subject Area:	Cardiovascular Disease
Award Type:	New Investigator Awards

Abstracts

Initial Award Abstract

Hematopoietic stem cells are the building blocks of both the blood and the immune system. They form the white cells, which fight infections, the red cells, which carry oxygen throughout the body, and the platelets, which promote healing. Hematopoietic stem cells are found in the bone marrow, where they continue to generate mature blood cells throughout our lives. Thus, any changes in the ability of stem cells to function normally could be deleterious to the body. Nicotine is one such factor that could result in serious alterations in the bone marrow microenvironment, resulting in an imbalance of the hematopoietic homeostasis and a changed ratio of mature cells in the blood. Indeed, transplantation of the bone marrow into the mice exposed to cigarette smoke results in a delay of the platelet recovery in the peripheral blood. In addition, our preliminary experiments show that the number of progenitor cells, which could develop into myeloid cells, is significantly reduced in animals exposed to cigarette smoke. Long-term bone marrow cultures treated with nicotine exhibit a lower count of non-adherent cells and delayed formation of hematopoietic foci within the adherent layer. Based on our preliminary observations, we propose to investigate how nicotine can alter the ability of bone marrow stromal cells to support proliferation and the differentiation of hematopoietic stem and progenitor cells into mature blood cells. In addition, we plan to examine the effects of nicotine on trafficking of murine hematopoietic stem/progenitor cells, including their rolling, adhesion and transendothelial migration through peripheral blood vessels.

This project will use the current knowledge in experimental hematology to understand the cellular and molecular mechanisms that affect hematopoietic cell function. We are confident that the planned studies will provide an explanation of how nicotine affects bone marrow cell functions. Studying the effect of nicotine on the bone marrow may open a new area of research that could ultimately establish a basis for novel therapeutic approaches to the treatment of tobacco-related diseases.

Publications

Exposure to nicotine during gestation results in impaired colonization of the bone marrow with fetal hematopoietic stem cells.
Periodical: American Society of Hematology			Index Medicus:
Authors: Orlovskaya IA, Toporkova LB, and Khaldoyanidi SK				ABS
Yr: 2002	Vol: 100	Nbr: 16	Abs: 4235	Pg: 184b

Hyaluronic acid facilitates recovery of hematopoiesis impaired by 5-fluouracil administration
Periodical: Stem Cells			Index Medicus:
Authors: Matrosova V, Orlovskaya I, Serobyan N, Khaldoyanidi S				ART
Yr: 2004	Vol: 22	Nbr:	Abs:	Pg: 542-553

Exposure to nicotine during gestation affects trafficking of fetal hematopoietic stem cells
Periodical: Blood			Index Medicus:
Authors: Khaldoyanidi S, Orlovskaya I				ABS
Yr: 2002	Vol: 100	Nbr: 16	Abs: #4235	Pg: 184b

Exposure to nicotine during gestation results in impaired colonization of the bone marrow with fetal hematopoietic stem cells.
Periodical: American Society of Hematology			Index Medicus:
Authors: Orlovskaya IA, Toporkova LB, and Khaldoyanidi SK				ABS
Yr: 2002	Vol: 100	Nbr: 16	Abs: 4235	Pg: 184b

Hyaluronic acid facilitates recovery of hematopoiesis impaired by 5-fluouracil administration
Periodical: Stem Cells			Index Medicus:
Authors: Matrosova V, Orlovskaya I, Serobyan N, Khaldoyanidi S				ART
Yr: 2004	Vol: 22	Nbr:	Abs:	Pg: 542-553

Exposure to nicotine during gestation affects trafficking of fetal hematopoietic stem cells
Periodical: Blood			Index Medicus:
Authors: Khaldoyanidi S, Orlovskaya I				ABS
Yr: 2002	Vol: 100	Nbr: 16	Abs: #4235	Pg: 184b