Differential homing and engraftment properties of hematopoietic progenitor cells from murine bone marrow, mobilized peripheral blood, and fetal liver

Szilvassy, Stephen J.; Meyerrose, Todd E.; Ragland, Penny L; Grimes, Barry

doi:10.1182/blood.v98.7.2108

Cited by 99 publications

(75 citation statements)

References 34 publications

(20 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These studies nevertheless show that the property governing the superior homing of MPB HPC to marrow is independent of accompanying mature leukocytes or of certain host conditions and lies within a cell population which is enriched for HPC. Although several studies have shown [45] or implied [46][47][48] the potential for superior marrow homing of MPB HPC, opposing views, showing similar [49] or even inferior [10] homing of MPB, have also been reported. Reasons for the discrepancies are not clear but may include insufficient sample size [49] and immunophenotypic instead of functional definition of HPC.…”

Section: Discussionmentioning

confidence: 99%

“…Although several studies have shown [45] or implied [46][47][48] the potential for superior marrow homing of MPB HPC, opposing views, showing similar [49] or even inferior [10] homing of MPB, have also been reported. Reasons for the discrepancies are not clear but may include insufficient sample size [49] and immunophenotypic instead of functional definition of HPC. [10] Well-established functional in vivo assays were used to compare marrow homing of CFU-C present in ssBM or MPB.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Hematopoietic Progenitor Cells (HPC) from Mobilized Peripheral Blood Display Enhanced Migration and Marrow Homing Compared to Steady-State Bone Marrow HPC

Bönig

Priestley

Oehler

et al. 2007

Experimental Hematology

View full text Add to dashboard Cite

Objective-Faster engraftment of G-CSF mobilized peripheral blood (MPB) transplants compared to steady-state bone marrow (ssBM) is well documented and clinically relevant. A number of different factors likely contribute to this outcome. In the present study we explored whether independent of cell number there are intrinsic differences in the efficiency of progenitor cell homing to marrow between MPB and ssBM. Methods-Mobilization was achieved by continuous infusion of G-CSF alone or in combination with other mobilizing agents.In vivo homing assays, in vitro migration assays, gene expression analysis and flow cytometry were utilized to compare homing-related in vivo and in vitro properties of MPB and ssBM HPC.Results-Marrow homing of murine MPB HPC, generated by different mobilizing schemes, was reproducibly significantly superior to that of ssBM, in lethally irradiated as well as in non-irradiated hosts. This phenotype was independent of MMP9, selectins, β2-and α4-integrins. Superior homing was also observed for human MPB HPC transplanted into NOD/SCIDβ2microglobulin-/-recipients. Inhibition of HPC migration abrogated the homing advantage of MPB but did not affect homing of ssBM HPC, whereas enhancement of motility by CD26 inhibition improved marrow homing only of ssBM HPC. Enhanced SDF-1 dependent chemotaxis and low CD26 expression on MPB HPC were identified as potential contributing factors. Significant contributions of the putative alternative SDF-1 receptor, RDC1, were unlikely based on gene expression data. Conclusion-The data suggest increased motility as a converging end point of complex changes seen in MPB HPC which is likely responsible for their favorable homing.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Hematopoietic Progenitor Cells (HPC) from Mobilized Peripheral Blood Display Enhanced Migration and Marrow Homing Compared to Steady-State Bone Marrow HPC

Bönig

Priestley

Oehler

et al. 2007

Experimental Hematology

View full text Add to dashboard Cite

show abstract

“…Most available reports only outlined the differences in the kinetics and efficiency of engraftment, in homing properties and in cell cycle profiles between mobilized blood stem cells and those isolated from resting BM. [10][11][12][13] In view of the increased use of peripheral blood stem cells in clinical transplant settings, it is of relevance to investigate long-term functioning of stem cells isolated from different sources. In this study, we directly assessed the function of MPB stem cells compared to control BM stem cells when co-transplanted in a single recipient mouse in an in vivo competitive repopulation assay.…”

Section: Introductionmentioning

confidence: 99%

Mobilized peripheral blood stem cells provide rapid reconstitution but impaired long-term engraftment in a mouse model

Yeoh

Ausema

Wierenga

et al. 2007

Bone Marrow Transplant

View full text Add to dashboard Cite

In this study, we use competitive repopulation to compare the quality and frequency of stem cells isolated from mobilized blood with stem cells isolated from bone marrow (BM) in a mouse model. Lin À Sca-1 þ c-Kit þ (LSK) cells were harvested from control BM and peripheral blood of mice following granulocyte colony-stimulating factor (G-CSF) administration. LSK cells were used because of their resemblance to human CD34 þ cells. We confirmed that transplantation of phenotypically defined mobilized peripheral blood (MPB) stem cells results in rapid recovery of blood counts. However, in vitro results indicated that LSK cells purified from MPB had lower cobblestone areaforming cell day 35 activity compared to BM. Additionally, evaluation of chimerism after co-transplantation of LSK cells purified from blood and BM revealed that MPB stem cells contained 25-fold less repopulation potential compared to BM stem cells. Competitive repopulating unit frequency analysis showed that freshly isolated MPB LSK cells have 8.8-fold fewer cells with long-term repopulating ability compared to BM LSK cells. Secondary transplantation showed no further decline in contribution of hematopoiesis relative to BM. We conclude that the reduced frequency of stem cells within the LSK population of MPB, rather than poorer quality, causes the reduced repopulation potential.

show abstract

“…In agreement with this, a ubiquitous expression of these integrins has been reported in less well-defined fetal HSPCs. 16,42,43 Integrin ␣6␤1 mediates FL LSK adhesion to lamininsIn in vitro adhesion assay (Figure 2), 10% to 15% of the isolated FL LSK cells adhered to recombinant laminin-411 and -511 isoforms and 25% adhered to placental laminin-511/521. Pretreatment of the cells with a protein kinase C activator, TPA, did not increase cell adhesion to the laminins (not shown).…”

mentioning

confidence: 99%

Distinct roles of integrins α6 and α4 in homing of fetal liver hematopoietic stem and progenitor cells

Qian

Georges-Labouesse

Nyström

et al. 2007

Blood

View full text Add to dashboard Cite

Homing of hematopoietic stem cells (HSCs) into the bone marrow (BM) is a prerequisite for establishment of hematopoiesis during development and following transplantation. However, the molecular interactions that control homing of HSCs, in particular, of fetal HSCs, are not well understood. Herein, we studied the role of the ␣6 and ␣4 integrin receptors for homing and engraftment of fetal liver (FL) HSCs and hematopoietic progenitor cells (HPCs) to adult BM by using integrin IntroductionDuring transplantation, intravenously injected hematopoietic stem and progenitor cells (HSPCs) selectively transmigrate through the sinusoidal walls into the bone marrow (BM) niches to engraft and reconstitute hematopoiesis. This process, called homing, is a rapid multistep process involving multiple adhesion receptor and ligand pairs, leading first to reversible adhesion of circulating HSPCs to endothelial cells of BM sinusoids and subsequently transmigration through the sinusoidal walls into the specific hematopoietic niches. 1 The adhesive interactions mediated by distinct receptors on hematopoietic cells regulate the localization, migration, and other HSPC functions within their native microenvironments, and are likely to define their homing potential in a transplantation setting. 2 The rate of reconstitution following transplantation varies depending on the source of hematopoietic stem cells (HSCs), suggesting developmentally regulated and cell type-specific differences in expression and function of homing receptors. Cord blood grafts are associated with a particularly delayed hematopoietic reconstitution. 3 In contrast, experimental studies have shown a more rapid and robust reconstitution of both human and mouse fetal liver (FL) HSCs than adult BM HSCs. 4,5 Increasing HSC homing and engraftment efficiency might offer a means to enhance reconstitution, which may be critically important if donor cell numbers are limiting, as frequently observed in cord blood units. 3 Therefore, knowledge of the specific molecular mechanisms involved in homing and engraftment of different types of HSPCs is of clinical significance for the development of clinical transplantation methods.Mouse models for mammalian hematopoiesis are widely used to study developmentally regulated HSC functions, including mobilization, homing, and engraftment. 6 During mammalian ontogeny, HSCs develop sequentially in distinct hematopoietic tissues, beginning in the yolk sac and subsequently in the aorta-gonadmesonephros region in the embryo proper. At embryonic day 10 (E10) in mice, definitive hematopoiesis arises in the liver, which is the main site of hematopoiesis throughout subsequent fetal development. 7 In later gestation, hematopoiesis expands into spleen (E15) and thereafter into BM (E17). This shift in hematopoiesis is accomplished by migration of liver HSPCs into spleen and BM, and consequently, is associated with mobilization of large numbers of HSPCs into the bloodstream. 6 Despite the central role of migration and homing in stem-cell biology and in st...

show abstract

Differential homing and engraftment properties of hematopoietic progenitor cells from murine bone marrow, mobilized peripheral blood, and fetal liver

Abstract: The rate of reconstitution following hematopoietic stem cell (HSC) transplantation differs widely depending on the tissue source of the cells infused. To test the hypothesis that variability in engraftment kinetics is related to differences in the efficiency with which intravenously trans-

Cited by 99 publications

References 34 publications

Hematopoietic Progenitor Cells (HPC) from Mobilized Peripheral Blood Display Enhanced Migration and Marrow Homing Compared to Steady-State Bone Marrow HPC

Hematopoietic Progenitor Cells (HPC) from Mobilized Peripheral Blood Display Enhanced Migration and Marrow Homing Compared to Steady-State Bone Marrow HPC

Mobilized peripheral blood stem cells provide rapid reconstitution but impaired long-term engraftment in a mouse model

Distinct roles of integrins α6 and α4 in homing of fetal liver hematopoietic stem and progenitor cells

Contact Info

Product

Resources

About