Project Details
Description
DESCRIPTION The long-term goal of this proposal is to elucidate the
mechanism(s) of the persistent anemia observed following severe trauma. Blood
loss is commonplace after trauma and repeated and multiple transfusions given
over several weeks are often necessary to correct a persistent anemia in
critically injured patients. Blood transfusions are immunosuppressive, carry
the risk of transmitting blood-borne infectious agents and are costly. Thus,
the ability to correct this anemia would be of great clinical importance. These
investigators and others have shown that endogenous erythropoietin levels are
elevated after injury, so the etiology and mechanism of this post-injury anemia
are likely to reside within the bone marrow (BM). Successful erythropoiesis
requires interaction between hematopoietic progenitor cells and the BM stroma
(the supporting matrix of the BM) within the BM microenvironment. To elucidate
the mechanisms of post-injury anemia, this proposal will investigate: (aim 1)
the effect of trauma on the growth and differentiation of BM progenitor cells.
In these studies bone marrow and peripheral blood from trauma patients and age
matched healthy volunteers will be obtained and the number and phenotype of the
progenitor cells determined. These cells will be cultured and assessed for
their ability to proliferate and differentiate into red blood cells. Adhesion
receptors which anchor these cells in the BM will also be evaluated. The
results of these experiments will be correlated to the patient demographics and
outcome; (aim 2) the effect of trauma on the ability of the BM stroma to grow
and support hematopoiesis. In this aim, BM from trauma patients and age matched
controls will be cultured to determine whether the BM stroma can grow to
confluence in a monolayer. Failure of the stroma to grow in culture been
demonstrated to correlate with BM failure in hematologic diseases. Stromal
monolayers will be cultured with BM progenitors to assess whether they can
support erythropoiesis and whether they produce extracellular matrix proteins
which help anchor the progenitor cells to the BM; (aim 3) The effect of plasma
on BM hematopoietic cellular progenitors, BM stroma, or both. In these studies
plasma obtained from trauma patients will be added to cultures of hematopoietic
progenitors or BM stroma and the growth will be compared to cultures grown with
normal plasma. A strength of the proposal is that a BM aspirate for an
individual patient can be utilized for both BM progenitor cell and stromal
cultures. In addition the effect of plasma from this patient will also be
studied; thus reults can be correlated with patient demographics and known
outcomes. This proposal is novel; there app[ear to have been no detailed
studies of BM erythropoietic function in trauma patients. Understanding the
mechanisms behind post-trauma anemia will allow therapeutic interventions
improving endogenous erythropoiesis to be targeted.
Status | Finished |
---|---|
Effective start/end date | 9/5/00 → 8/31/06 |
Funding
- National Heart, Lung, and Blood Institute: $314,000.00
- National Heart, Lung, and Blood Institute: $304,376.00
- National Heart, Lung, and Blood Institute: $314,000.00
- National Heart, Lung, and Blood Institute: $314,000.00
ASJC
- Cell Biology
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