HUMAN UMBILICAL CORD BLOOD STEM CELLS AND IMMUNOLOGY

Project: Research project

Description

Our laboratory played a major role in deriving the laboratory data and in
coordinating the cooperative effort that led to the successful uses of
single collections of human umbilical cord blood, as an alternative to
adult bone marrow, for provision of HLA-matched allogeneic sibling
stem/progenitor cells in 3 children with Fanconi anemia. This grant
application is a joint effort to evaluate hematologically and
immunologically the hypothesis that cord blood cells have a broader basis
for use in other disorders currently treated with bone marrow, including
adults as well as children. We propose to: 1) measure total hematopoietic
stem/progenitor cells in human umbilical cord blood collections by, a) in
vitro methodologies with new and currently used growth factors and modified
culture conditions to enhance detection of early hematopoietic and more
lineage restricted cells, and b) in vivo using immunodeficient (SCID,
bg/nu/xid) mice as recipients for human hematopoietic repopulating cells,
2) expand cord blood stem/progenitor cells using various cytokines that can
stimulate, enhance, or suppress various stages of their production, as
assessed by the above in vitro and in vivo assays, 3) investigate the
quantitative and qualitative expression of polymorphic antigens on the
progenitors using allo-antibodies to HLA-class I and class II antigens,
modulation of these antigens, and susceptibility of progenitors to
antigen-specific lysis or growth inhibition by cloned cytotoxic
T-lymphocytes against major- and minor-histocompatibility antigens, 4)
investigate reactivity of these cells to certain allo-antigens, especially,
the cytotoxic T-lymphocyte precursor cell frequency directed against
several polymorphic antigens against various related and unrelated
individuals, and 5) investigate whether cord blood cells exhibit an
antileukemic reactivity against leukemic cells and clonogenic leukemic
precursor cells. Adult bone marrow will be comparatively analyzed in the
above 5 aims. These studies will provide information on numbers of
stem/progenitors in single collections, expansion of such cells in vitro,
whether such cells have decreased immunological reactivity allowing them to
be used to advantage in situations with reduced graft verses host disease,
perhaps in haplo-identical transplants, but with maintenance of
antileukemic cell reactivity.
StatusFinished
Effective start/end date5/1/912/28/95

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $179,542.00
  • National Institutes of Health: $195,516.00

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Allergy and Immunology
Fetal Blood
Blood Cells
Stem Cells
Antigens
Bone Marrow
Minor Histocompatibility Antigens
Transplants
Fanconi Anemia
Histocompatibility Antigens Class II
Cytotoxic T-Lymphocytes
Intercellular Signaling Peptides and Proteins
Maintenance
Lymphocytes
Cytokines
Antibodies
Growth

ASJC

  • Medicine(all)