Haemopoietic stem cells: spleen colony‐forming cells are normally actively proliferating

Nečas, E; Znojil, Vladimı́r; Šefc, Luděk

doi:10.1111/j.1365-2184.1990.tb01351.x

Cited by 5 publications

(7 citation statements)

References 11 publications

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“…Hematopoietic progenitors, detected as CFU-S ( Figure 3) as well as STRC up to 1 month after BMT (Figure 1), were more susceptible to damage by ischemia than LTRC. This is in agreement with their higher proliferation and likely metabolic activity [28,29].…”

Section: Discussionsupporting

confidence: 86%

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Hematopoietic Stem Cells Survive Circulation Arrest and Reconstitute Hematopoiesis in Myeloablated Mice

Michalova

Savvulidi

Šefc

et al. 2011

Biology of Blood and Marrow Transplantation

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Hematopoietic stem and progenitor cells (HSPC) for bone marrow transplantation are currently obtained directly from living voluntary donors or from cord blood units. However, a suitable donor is not always found. Because HSPC are known for their relative resistance to hypoxia, using an experimental murine model, we explored cadaveric bone marrow (BM) as their alternative source. After donor mice were sacrificed, BM was left in intact femurs at 37°C, 20°C, or 4°C under ischemic conditions, resulting in combined oxygen and metabolic substrate shortage and the accumulation of metabolic waste products. BM cells were harvested after a set time period ranging from 0 to 48 hours. To determine the impact of delayed harvesting on the transplantability of HSPC, a competitive repopulation assay using a murine Ly5.1/Ly5.2 congenic model in 2 different settings was used: after submyeloablative (6 Gy) or myeloablative (9 Gy) total-body irradiation, Ly5.2 hosts received cadaveric Ly5.1 cells or a mixture of cadaveric Ly5.1 cells and fresh Ly5.2 cells in a 1:1 ratio. Chimerism resulting from cadaveric donor cells, followed up to 6 months after transplantation, proved that the long-term repopulation ability of HSPC was fully preserved for 2 hours, 6 hours, and 12 hours at 37°C, 20°C, and 4°C of ischemia, respectively. A colony-forming unit-spleen (CFU-S) clonogenic assay revealed a higher sensitivity of proliferating hematopoietic progenitors to ischemia compared to repopulating cells (STRC and LTRC). Flow cytometry analysis of apoptosis in cadaveric BM demonstrated that the LSK (Lin(low)Sca-1(+)c-Kit(+)) subpopulation, enriched in HSPC, contained less apoptotic and dead cells than the BM as a whole. Furthermore, the number of LSK SLAM (CD150(+)CD48(-)) and LSK SP (side population) cells (fractions highly enriched in hematopoietic stem cells) decreased in parallel with BM transplantability. As well as cadaveric BM cells, we also tested the transplantability and survival of BM cells after storage in a suspension in vitro without specific hematopoietic growth factors. HSPC did not display any decrease in transplantability after 2 days of storage at 37°C or 4 days at 4°C. A higher sensitivity of progenitors to unfavorable conditions was observed again using CFU-S and granulocyte macrophage-colony forming cell (GM-CFC) assays, especially at 37°C. This paper shows that HSPC survive the cessation of circulation for a considerable time and maintain their engraftment potential. This time is significantly extended with in vitro storage compared to the cadaveric BM.

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Section: Discussionsupporting

confidence: 86%

“…Because .50% of differentiated blood precursor cells proliferate actively [29], the result appears to reflect a particular proliferation rate. This explanation is also supported by the decline in proliferating CFU-S [28], which roughly correlated to the increase number of dead and apoptotic BM cells.…”

Section: Discussionmentioning

confidence: 62%

Hematopoietic Stem Cells Survive Circulation Arrest and Reconstitute Hematopoiesis in Myeloablated Mice

Michalova

Savvulidi

Šefc

et al. 2011

Biology of Blood and Marrow Transplantation

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“…A similar diagram is shown for CBF, mice in Figure 2B (the original data, obtained during 8 months of experiments, were presented in [27]). The correlation was again negative, positive or zero at various stages of the recovery.…”

Section: Correlation Between Cfu-s Numbers and The Fraction Synthesizsupporting

confidence: 52%

“…Recent research showed that CFU-S are not the ultimate stem cells [8-101 supposed to maintain their numbers and thus convey the functional longevity onto the hematopoietic tissue. Therefore, it is not surprising that detailed evaluation of experimental data no longer supports a close dependence of the CFU-S proliferation on CFU-S numbers [22,34, this paper] and an always low CFU-S proliferation in normal mice [27,29].…”

Section: Discussionmentioning

confidence: 99%

On control of the hematopoietic cell proliferation

Nečas

Šefc²,

Znojil

1993

STEM CELLS

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Hematopoietic cells, detected as spleen colony forming units (CFU-S), vary in their proliferation rate, and this can be investigated in vivo by determining the fraction of CFU-S synthesizing DNA. A large number of measurements of CFU-S number and the fraction synthesizing DNA has been obtained under standardized conditions in normal mice and after a single dose of arabinosyl cytosine (ara-C). These data are analyzed with respect to the correlation between the number of CFU-S and their DNA-synthesizing fraction since, in the past, it has been maintained that the CFU-S proliferation rate responds sensitively to changes in CFU-S numbers. The present analysis does not support this traditional view--it instead demonstrates that natural variations in CFU-S numbers occurring in the same range as those following ara-C do not trigger CFU-S proliferation. On the other hand, administration of ara-C triggers most of the surviving CFU-S into the cell cycle, while decreasing CFU-S numbers by only about 40%. Data are also presented showing changes of CFU-S numbers and their DNA-synthesizing fraction in mice given a single dose of cyclophosphamide (CY). CY reduces CFU-S numbers, but the fraction synthesizing DNA can be either increased or decreased depending on time after treatment. Both these experimental situations argue against a close relationship between CFU-S numbers and their proliferation rate and suggest a different or a more complex regulation.

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“…Also the phenotype of HSPC, defined as LSK SLAM (LSK CD150 + CD48cells), 13 was present as long as their transplantability was maintained. 12 Actively proliferating progenitors 14,15 tested as either CFU-S or GM-CFC, were more sensitive to ischemia or storage in suspension than the hematopoietic stem cells, which provide long-term donor chimerism. If cadaveric HSPC from the human bone marrow were also shown to be utilizable for transplantation, a new repository of bone marrow cells could be established.…”

mentioning

confidence: 99%

Cadaveric bone marrow as potential source of hematopoietic stem cells for transplantation

Michalova

Savvulidi²,

Šefc³

et al. 2011

Chimerism

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Every year, bone marrow transplantation saves many lives worldwide. Unfortunately, a suitable donor is not always available. Since organs are routinely harvested from cadaveric organ donors, we decided to assess such a possibility for bone marrow. We analyzed the functional properties and phenotypic markers of murine hematopoietic stem and progenitor cells (HSPC) from cadaveric bone marrow and during storage in vitro in a suspension. It was demonstrated that HSPC exposed to a warm or cold ischemia in intact femur did not lose their phenotype and maintained their repopulating ability for two to twelve hours depending on the temperature. Additionally, fresh bone marrow remained fully viable in cell suspension for two days or four days at 37°C or 4°C, respectively. Based on these findings, cadaveric bone marrow could be considered as an alternative source of hematopoietic stem cells for transplantation.

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Haemopoietic stem cells: spleen colony‐forming cells are normally actively proliferating

Cited by 5 publications

References 11 publications

Hematopoietic Stem Cells Survive Circulation Arrest and Reconstitute Hematopoiesis in Myeloablated Mice

Hematopoietic Stem Cells Survive Circulation Arrest and Reconstitute Hematopoiesis in Myeloablated Mice

On control of the hematopoietic cell proliferation

Cadaveric bone marrow as potential source of hematopoietic stem cells for transplantation

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