Use of long-term human marrow cultures to demonstrate progenitor cell precursors in marrow treated with 4-hydroperoxycyclophosphamide
The continued retrieval of progenitor cells (CFU-GEMM, BFU-E, CFU-E, CFU-GM) from human long-term marrow cultures (LTMC) is not uncommonly used as evidence that proliferation and differentiation are occurring in more primitive hematopoietic stem cells (HSC) in these cultures. Alternatively, the continued presence of progenitors in LTMC could be the result of survival and/or limited self-renewal of progenitor cells present when the culture was initiated, and such progenitors would have little relevance to the parent HSC. The following studies were designed to determine the relative contributions of precursors of progenitor cells to the total progenitor cells present in LTMC using a two-stage regeneration model. The adherent layer in LTMC was established over 3 weeks, irradiated (875 rad) to permanently eliminate resident hematopoietic cells, and recharged with autologous cryo-preserved marrow that was either treated or not treated (control) with 4-hydroperoxycyclophosphamide (4-HC, 100 micrograms/ml for 30 min). The 4-HC-treated marrow contained no progenitor cells, yet based on clinical autologous bone marrow transplant experience, has intact HSC. Within 1-3 weeks, progenitor cells reappeared in the irradiated LTMC recharged with 4-HC-treated marrow, and were preferentially located in the adherent layer. By 2-6 weeks, the number of progenitor cells in the adherent layer of LTMC recharged with 4-HC marrow was equivalent to control LTMC. The progenitors regenerating in the irradiated LTMC recharged with 4-HC-treated marrow appear to originate from precursors of progenitor cells, perhaps HSC. We propose this model may be useful in elucidating cellular and molecular correlates of progenitor cell regeneration from precursors.
- Research Organization:
- Emory Univ. School of Medicine, Atlanta, GA
- OSTI ID:
- 6274250
- Journal Information:
- Exp. Hematol.; (United States), Vol. 15:6
- Country of Publication:
- United States
- Language:
- English
Similar Records
Lineage-related cytotoxicity and clonogenic profile of 1,4-benzoquinone-exposed hematopoietic stem and progenitor cells
Formaldehyde and co-exposure with benzene induce compensation of bone marrow and hematopoietic stem/progenitor cells in BALB/c mice during post-exposure period
Related Subjects
BONE MARROW CELLS
ADHESION
IRRADIATION
STEM CELLS
CELL PROLIFERATION
BIOLOGICAL MODELS
BLOOD FORMATION
CELL CULTURES
ENDOXAN
FREEZING
MAN
PRECURSOR
ALKYLATING AGENTS
ANIMAL CELLS
ANIMALS
CONNECTIVE TISSUE CELLS
DRUGS
IMMUNOSUPPRESSIVE DRUGS
MAMMALS
PRIMATES
SOMATIC CELLS
VERTEBRATES
560120* - Radiation Effects on Biochemicals
Cells
& Tissue Culture