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Title: Stromal cell migration precedes hemopoietic repopulation of the bone marrow after irradiation

Abstract

Circulation of hemopoietic stem cells into an irradiated site has been thoroughly documented, but migration of stromal cells to repair radiation damage has not. We determined the radiosensitivity of mouse bone marrow stroma and evaluated stromal and hemopoietic repopulation in x-irradiated marrow. The D/sub 0/ for growth of colonies of marrow stromal cells (MSC) was 215 to 230 rad. Total-body irradiation (TB) obliterated marrow stromal and hemopoietic cells within 3 days. In contrast, 1 day after 1000 rad leg irradiation (LI), MSC rose to 80% of normal, but fell to 34% by 3 days and recovered to 72% by 30 days. However, femoral nucleated cells diminished to 20% by 3 days and recovered to 74% of normal by 30 days. Likewise, differentiated marrow cells and hemopoietic stem cells were initially depleted. With 1000 rad LI followed 3 h later by 1000 rad to the body while shielding the leg, MSC and femoral nucleated cells recovered to values intermediate between 1000 rad TB and 1000 rad LI. We concluded that: (1) the D/sub 0/ for MSC was 215 to 230 rad, (2) stromal repopulation preceded hemopoietic recovery, and (3) immigration of stromal cells from an unirradiated sanctuary facilitated hemopoietic repopulation ofmore » a heavily irradiated site.« less

Authors:
; ; ;
Publication Date:
Research Org.:
Univ. of Iowa, Iowa City
OSTI Identifier:
5323153
Resource Type:
Journal Article
Resource Relation:
Journal Name: Radiat. Res.; (United States); Journal Volume: 81:1
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.; 59 BASIC BIOLOGICAL SCIENCES; BONE MARROW; RADIOSENSITIVITY; BONE MARROW CELLS; X RADIATION; BIOLOGICAL RADIATION EFFECTS; BIOLOGICAL RECOVERY; BLOOD CIRCULATION; COLONY FORMATION; COMPARATIVE EVALUATIONS; DOSE-RESPONSE RELATIONSHIPS; EXPERIMENTAL DATA; ISOLATED VALUES; MICE; MIGRATION; PARTIAL BODY IRRADIATION; STEM CELLS; SURVIVAL CURVES; WHOLE-BODY IRRADIATION; ANIMAL CELLS; ANIMALS; BIOLOGICAL EFFECTS; BODY; CONNECTIVE TISSUE CELLS; DATA; DATA FORMS; ELECTROMAGNETIC RADIATION; EXTERNAL IRRADIATION; HEMATOPOIETIC SYSTEM; INFORMATION; IONIZING RADIATIONS; IRRADIATION; MAMMALS; NUMERICAL DATA; ORGANS; RADIATION EFFECTS; RADIATIONS; RECOVERY; RODENTS; SOMATIC CELLS; TISSUES; VERTEBRATES; 560121* - Radiation Effects on Cells- External Source- (-1987); 560152 - Radiation Effects on Animals- Animals; 551000 - Physiological Systems

Citation Formats

Werts, E.D., Gibson, D.P., Knapp, S.A., and DeGowin, R.L. Stromal cell migration precedes hemopoietic repopulation of the bone marrow after irradiation. United States: N. p., 1980. Web. doi:10.2307/3575360.
Werts, E.D., Gibson, D.P., Knapp, S.A., & DeGowin, R.L. Stromal cell migration precedes hemopoietic repopulation of the bone marrow after irradiation. United States. doi:10.2307/3575360.
Werts, E.D., Gibson, D.P., Knapp, S.A., and DeGowin, R.L. 1980. "Stromal cell migration precedes hemopoietic repopulation of the bone marrow after irradiation". United States. doi:10.2307/3575360.
@article{osti_5323153,
title = {Stromal cell migration precedes hemopoietic repopulation of the bone marrow after irradiation},
author = {Werts, E.D. and Gibson, D.P. and Knapp, S.A. and DeGowin, R.L.},
abstractNote = {Circulation of hemopoietic stem cells into an irradiated site has been thoroughly documented, but migration of stromal cells to repair radiation damage has not. We determined the radiosensitivity of mouse bone marrow stroma and evaluated stromal and hemopoietic repopulation in x-irradiated marrow. The D/sub 0/ for growth of colonies of marrow stromal cells (MSC) was 215 to 230 rad. Total-body irradiation (TB) obliterated marrow stromal and hemopoietic cells within 3 days. In contrast, 1 day after 1000 rad leg irradiation (LI), MSC rose to 80% of normal, but fell to 34% by 3 days and recovered to 72% by 30 days. However, femoral nucleated cells diminished to 20% by 3 days and recovered to 74% of normal by 30 days. Likewise, differentiated marrow cells and hemopoietic stem cells were initially depleted. With 1000 rad LI followed 3 h later by 1000 rad to the body while shielding the leg, MSC and femoral nucleated cells recovered to values intermediate between 1000 rad TB and 1000 rad LI. We concluded that: (1) the D/sub 0/ for MSC was 215 to 230 rad, (2) stromal repopulation preceded hemopoietic recovery, and (3) immigration of stromal cells from an unirradiated sanctuary facilitated hemopoietic repopulation of a heavily irradiated site.},
doi = {10.2307/3575360},
journal = {Radiat. Res.; (United States)},
number = ,
volume = 81:1,
place = {United States},
year = 1980,
month = 1
}
  • The recovery of fibroblastic colony-forming units (CFU-F) in murine bone marrow hemopoietic stroma was studied during eighteen months after 9 Gy lethal total-body irradiation and reconstitution with syngeneic bone marrow cells. After an initial depletion, CFU-F numbers increased from 10% of normal values at three months to 40% at 18 months after treatment, irrespective of graft size and presence of CFU-F in the graft. Fourteen months after treatment 35% of all CFU-F present in the recipients bone marrow was donor-derived independent of graft size. When mice were treated with high-dose lipopolysaccharide-W three months after irradiation and bone marrow transplantation, CFU-Fmore » numbers decreased to hardly detectable levels within one day, and then recovered to normal numbers four weeks later--whereas radiation control mice still had low CFU-F numbers. These data suggest that after lethal total-body irradiation the stroma still contained viable fibroblastic cells that had lost their in vitro colony-forming capacity as a result of radiation damage. In consequence there was no need for replacement of these fibroblastic cells by donor-derived or host-derived CFU-F. Only depletion of CFU-F from the bone marrow, as was induced with lipopolysaccharide, stimulated repopulation of the stroma with colony-forming fibroblastic cells.« less
  • Stromal cell lines, designated MS-1, -2, -3, -4, -5, -6, and -7 were established by irradiating the adherent cells in long-term bone marrow cultures with 900-rad x-rays. Two of the cell lines, MS-1 and MS-5, have the capacity to support the growth of hemopoietic stem cells (spleen colony-forming cells and granulocyte-macrophage colony-forming cells) for greater than 2 months in vitro. These two cell lines were alkaline phosphatase-, peroxidase-, and factor VIII-negative and positive for periodic acid-Schiff and nonspecific esterase. Extracellular matrix proteins such as fibronectin, laminin, and collagen type I were produced by these two cell lines. Neither MS-1 cell-more » nor MS-5 cell-conditioned medium supported the growth of hemopoietic stem cells, and hemopoietic stem cells were found preferentially to be under and on MS-1 and MS-5 layers rather than in suspension. Close contact with the MS-1 cell layer or the MS-5 cell layer appears to be essential in maintaining hemopoiesis in vitro. Conditioned media from MS-1 cells and MS-5 cells stimulated granulocyte colony formation from murine bone marrow cells in semisolid culture.« less
  • To evaluate some of the microenvironmental conditions necessary to support hemopoiesis, the right femurs of mice were x-irradiated. Femoral radioiron uptake in the right femur after 1000 rad fell to 20 +- 2 percent of the control (mean +- 1 SEM) at 3 days and returned to 67 +- 5 percent by 6 months. Erythroblast counts reflected these changes. Total nucleated cell counts initially diminished to 21 +- 3 percent of the control but increased to 76 +- 6 percent of normal by 6 months. Counts of bone marrow stromal cells in culture rose from 13 +- 4 percent ofmore » the control at 3 days to 77 +- 11 percent by 6 months. In contrast, except for temporary elevation in /sup 59/Fe uptake at 1 week, animals receiving 5000 or 10,000 rad to the right femur had persistently low levels (less than 30%) of total nucleated cell counts, stromal cell counts, /sup 59/Fe uptake, and erythroblast counts over 6 months. In the unirradiated marrow of these animals, the radioiron uptake and erythroblast counts were less than normal, and the total nucleated cell counts and splenic /sup 59/Fe uptake and weights were above normal through 6 months. We conclude that 5000 or 10,000 rad inhibited sustained recovery of hemopoietic cells and stromal cells, 1000 rad permitted slightly subnormal hemopoietic repopulation and stromal cell recovery, the unirradiated marrow and spleen underwent dose- and time-dependent changes.« less
  • We have studied the in vivo spleen colony-forming ability and marrow repopulating ability of murine bone marrow cells differing in mitochondrial activity. Following centrifugal elutriation the cells were sorted on the basis of rhodamine-123 fluorescence intensity within a predetermined light scatter window. It is shown that a class of hemopoietic stem cells exists that differs from the majority of day-12 spleen colony-forming units (CFU-S) in that it has low mitochondrial activity and a high capacity to generate in time new day-12 CFU-S and cells that rescue recipients from radiation-inflicted death. These data add direct evidence for the identity of pre-CFU-Smore » and CFU-S by physical separation.« less