scholarly journals Effects of Radiation on The Capacity of The Stem Cell Compartment to Differentiate into Granulocytic and Erythrocytic Progeny

Blood ◽  
1969 ◽  
Vol 34 (2) ◽  
pp. 141-156 ◽  
Author(s):  
SAMUEL HELLMAN ◽  
HELEN E. GRATE ◽  
JOHN T. CHAFFEY
Keyword(s):  
Stem Cell ◽  
Cell Compartment ◽  
Hematopoietic Stem ◽  
Stem Cell Proliferation ◽  
Cell Counts ◽  
Stem Cell Compartment ◽  
Cell Pool ◽  
White Blood Cell Counts ◽  
Effects Of Radiation ◽  
Stem Cell Pool

Abstract Different methods have been used to measure the survival following radiation of the hematopoietic stem cell pool. Two of these systems measure the stem cell pool by its ability to proliferate and differentiate into mature progeny. In both methods, irradiated recipient mice receive syngeneic bone marrow. A period of time is allowed for the transplanted progenitor cells to divide and differentiate, and then the progeny produced are assayed. Ability to form red blood cells is assessed by the amount of radioactive iron incorporated into newly-formed erythrocytes. Capacity for granulocyte formation is measured by peripheral white blood cell counts following endotoxin stimulation. This latter is a granulocyte response and has been shown to be a measure of the marrow granulocyte reserve. The pool as measured by its ability to produce erythrocytic progeny appears to be more sensitive initially than as measured by its ability to produce granulocytic progeny. Erythropoietic repopulating ability begins recovery more promptly than the granulopoietic. These effects appear to be due to the host milieu rather than any direct effect of radiation on the stem cells, resulting in initial conservation of granulopoiesis relative to erythropoiesis with subsequent compensatory recovery of erythropoiesis. Because of recent evidence suggesting a common stem cell, these results are interpreted as consistent with the notion that radiation affects not only stem cell proliferation, but also the direction and extent of differentiation.

scholarly journals Effect of Cyclophosphamide on the Murine Hematopoietic Stem Cell Compartment as Measured by Different Assay Techniques

Blood ◽  
1971 ◽  
Vol 38 (6) ◽  
pp. 706-714 ◽  
Author(s):  
SAMUEL HELLMAN ◽  
HELEN E. GRATE
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Erythroid Differentiation ◽  
Cell Compartment ◽  
Hematopoietic Stem ◽  
Cell Counts ◽  
Cell Pool ◽  
Murine Hematopoietic Stem Cell ◽  
White Blood Cell Counts ◽  
Stem Cell Pool

Abstract Three different methods have been used to measure the survival of the hematopoietic stem cell pool following treatment with cyclophosphamide. Two of these systems measure the stem cell pool by its ability to proliferate and differentiate into mature progeny. In both these methods irradiated recipient mice receive syngeneic bone marrow from either normal or cyclophosphamide-treated animals. A period of time is allowed for the transplanted progenitor cells to divide and differentiate, and then the progeny produced are assayed. Ability to form red blood cells is assessed by the amount of radioactive iron incorporated into newly formed erythrocytes. Capacity for granulocyte formation is measured by peripheral white blood cell counts following endotoxin stimulation. The pool as measured by its ability to produce erythrocytic progeny appears to be more sensitive than as measured by its ability to produce granulocytic progeny. The spleen colony assay gives results similar to the assay of granulocytic progeny. These results, taken with previous data indicating decrease in erythroid precursors in spleen colonies derived from cells surviving cyclophosphamide, are interpreted as indicating a decrease in ability for erythroid differentiation in cells surviving cyclophosphamide.

Genetic control of hematopoietic stem cell frequency in mice is mostly cell autonomous

Blood ◽  
2000 ◽  
Vol 95 (7) ◽  
pp. 2446-2448 ◽  
Author(s):  
Christa E. Müller-Sieburg ◽  
Rebecca H. Cho ◽  
Hans B. Sieburg ◽  
Sergey Kupriyanov ◽  
Roy Riblet
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Compartment ◽  
Cell Frequency ◽  
Hematopoietic Stem ◽  
Stem Cell Compartment ◽  
Cell Pool ◽  
The Difference ◽  
Extrinsic Effects ◽  
Stem Cell Pool

Abstract Previously we reported that the size of the stem cell compartment (measured as LTC-IC) is 11-fold greater in DBA/2 than in C57BL/6 mice, and we identified genes that regulate the size of the stem cell pool. To determine whether stem cell intrinsic or extrinsic events account for these differences, we created chimeras by aggregating morulae from the strains C57BL/6 and DBA/2. In these chimeras stem cells of both genotypes are exposed to a common mixed environment. Thus, an equalization of stem cell frequencies is expected if stem cell extrinsic effects dominate. Conversely, the parental ratio of LTC-IC should be preserved if the regulation is stem cell autonomous. For each chimera, individual LTC-IC were genotyped on the clonal levels by analyzing their progeny. We found that most of the difference that regulates the size of the stem cell compartment was intrinsic.

Genetic control of hematopoietic stem cell frequency in mice is mostly cell autonomous

Blood ◽  
2000 ◽  
Vol 95 (7) ◽  
pp. 2446-2448 ◽  
Author(s):  
Christa E. Müller-Sieburg ◽  
Rebecca H. Cho ◽  
Hans B. Sieburg ◽  
Sergey Kupriyanov ◽  
Roy Riblet
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Compartment ◽  
Cell Frequency ◽  
Hematopoietic Stem ◽  
Stem Cell Compartment ◽  
Cell Pool ◽  
The Difference ◽  
Extrinsic Effects ◽  
Stem Cell Pool

Previously we reported that the size of the stem cell compartment (measured as LTC-IC) is 11-fold greater in DBA/2 than in C57BL/6 mice, and we identified genes that regulate the size of the stem cell pool. To determine whether stem cell intrinsic or extrinsic events account for these differences, we created chimeras by aggregating morulae from the strains C57BL/6 and DBA/2. In these chimeras stem cells of both genotypes are exposed to a common mixed environment. Thus, an equalization of stem cell frequencies is expected if stem cell extrinsic effects dominate. Conversely, the parental ratio of LTC-IC should be preserved if the regulation is stem cell autonomous. For each chimera, individual LTC-IC were genotyped on the clonal levels by analyzing their progeny. We found that most of the difference that regulates the size of the stem cell compartment was intrinsic.

Hematopoietic stem cell compartment: Acute and late effects of radiation therapy and chemotherapy

1995 ◽  
Vol 31 (5) ◽  
pp. 1319-1339 ◽  
Author(s):  
Peter Mauch ◽  
Louis Constine ◽  
Joel Greenberger ◽  
William Knospe ◽  
Jessie Sullivan ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Late Effects ◽  
Cell Compartment ◽  
Hematopoietic Stem ◽  
Stem Cell Compartment ◽  
Effects Of Radiation

scholarly journals Permanent loss in stem cell self renewal capacity following stress to the marrow

Blood ◽  
1988 ◽  
Vol 72 (4) ◽  
pp. 1193-1196 ◽  
Author(s):  
P Mauch ◽  
M Rosenblatt ◽  
S Hellman
Keyword(s):  
Stem Cell ◽  
Hind Limb ◽  
Cell Function ◽  
Cell Compartment ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Stem Cell Compartment ◽  
Permanent Loss ◽  
Marrow Cellularity ◽  
Stem Cell Pool

A technique of irradiating the entire mouse except for one hind limb was developed to provide repeated proliferative demand on the stem cell pool. Animals received 200 cGY weekly for a total dose of 3,400 to 4,000 cGy. During irradiation, shielded bone marrow cellularity was similar to that of unirradiated controls. Shielded marrow colony- forming unit (CFUs) content increased while marrow CFUs self renewal capacity decreased as compared with unirradiated age-matched controls. Following irradiation experimental animals were monitored monthly for 10 to 12 months for marrow cellularity, CFUs content, and self renewal capacity. Shielded marrow cellularity and CFUs content remained elevated over age-matched controls throughout the period of observation. These findings are compatible with the requirement of the shielded hind limb to provide hematopoietic support for the remainder of the animal. Shielded marrow self renewal capacity, a measurement reflecting primitive hematopoietic stem cell function, remained depressed and did not recover with time. These experiments provide evidence for there being limitations on the self renewal capacity of the stem cell compartment. While the small amount of shielded marrow had sufficient capacity to support the animal its average self renewal capacity was permanently reduced.

scholarly journals Permanent loss in stem cell self renewal capacity following stress to the marrow

Blood ◽  
1988 ◽  
Vol 72 (4) ◽  
pp. 1193-1196 ◽  
Author(s):  
P Mauch ◽  
M Rosenblatt ◽  
S Hellman
Keyword(s):  
Stem Cell ◽  
Hind Limb ◽  
Cell Function ◽  
Cell Compartment ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Stem Cell Compartment ◽  
Permanent Loss ◽  
Marrow Cellularity ◽  
Stem Cell Pool

Abstract A technique of irradiating the entire mouse except for one hind limb was developed to provide repeated proliferative demand on the stem cell pool. Animals received 200 cGY weekly for a total dose of 3,400 to 4,000 cGy. During irradiation, shielded bone marrow cellularity was similar to that of unirradiated controls. Shielded marrow colony- forming unit (CFUs) content increased while marrow CFUs self renewal capacity decreased as compared with unirradiated age-matched controls. Following irradiation experimental animals were monitored monthly for 10 to 12 months for marrow cellularity, CFUs content, and self renewal capacity. Shielded marrow cellularity and CFUs content remained elevated over age-matched controls throughout the period of observation. These findings are compatible with the requirement of the shielded hind limb to provide hematopoietic support for the remainder of the animal. Shielded marrow self renewal capacity, a measurement reflecting primitive hematopoietic stem cell function, remained depressed and did not recover with time. These experiments provide evidence for there being limitations on the self renewal capacity of the stem cell compartment. While the small amount of shielded marrow had sufficient capacity to support the animal its average self renewal capacity was permanently reduced.

scholarly journals The Effect of Postirradiation Bleeding or Endotoxin on Proliferation and Differentiation of Hematopoietic Stem Cells

Blood ◽  
1972 ◽  
Vol 40 (3) ◽  
pp. 375-389 ◽  
Author(s):  
Sallie S. Boggs ◽  
Paul A. Chervenick ◽  
Dane R. Boggs
Keyword(s):  
Stem Cell ◽  
Cell Compartment ◽  
Hematopoietic Stem ◽  
Split Dose ◽  
Stem Cell Compartment ◽  
Proliferation And Differentiation ◽  
Early Rise ◽  
Short Time ◽  
And Control ◽  
Self Replication

Abstract Bleeding after irradiation failed to affect the time of onset or rate of regeneration of the hematopoietic stem cell compartment as measured by a split-dose irradiation method. Bleeding after a single 600 rad exposure hastened the time of onset of erythropoiesis as measured by spleen colonies and 59Fe uptake, but the early rise was abortive and the second increase began at the same time as the first increase seen in irradiated controls. The largest abortive increase was seen when bleeding occurred within 4 hr of irradiation. Lesser effects were seen when bleeding occurred 12 or 24 hr after and no effect 48 hr after irradiation. A generation time of 6.4 hr for a colony-forming cell that forms a colony in 4 days was calculated from the estimated number of cells in one such colony. Injection of cytosine arabinoside at the time of bleeding reduced colony numbers and 59Fe uptake equally in bled and control mice. Injection of 25 µg Salmonella typhosa endotoxin just after irradiation produced a similar early abortive rise in microscopic granulocytic colonies. These results are compatible with a model for pluripotential stem cell compartment in which: (1) differentiation and self-replication occur concomitantly unless the compartment is reduced below approximately 1O% of normal size; then self-replication occurs without appreciable differentiation; (2) for a short time (∼ 24 hr) after depletion below the threshold, differentiation can occur in response to strong stimuli.

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