Detection of a Stem Cell Population with Hemangioblastic Characteristics in Primary Myelofibrosis (PMF),

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3860-3860
Author(s):  
Ioanna N Trivai ◽  
Thomas Stuebig ◽  
Anita Badbaran ◽  
Ursula Gehling ◽  
Asterios Tsiftsoglou ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Peripheral Blood ◽  
Primary Myelofibrosis ◽  
Jak2v617f Mutation ◽  
Cell Subpopulation ◽  
Stem Cell Population ◽  
Allele Burden

Abstract Abstract 3860 Primary myelofibrosis (PMF) comprises a myeloproliferative neoplasia accompanied by imbalance of various tissues of the mesoderm, let alone the hematopoietic tissue. Involvement of multiple hematopoietic lineages during disease progression suggests the clonality of myelofibrosis that can be attributed to an initial stem cell defect at the very early stage of the stem cell hierarchy. Hematopoietic and endothelial phenotypes of circulating multipotent stem cells in patient peripheral blood, along with the increased microvascular density in the bone marrow, leads to the hypothesis that the critical event in PMF involves malignant transformation of a stem cell with hemangioblastic potential. Former studies have provided functional evidence that activated JAK2 signalling in primitive human hematopoietic cells is sufficient to drive key processes involved in the pathogenesis of the disease. In this study, the functionality and differentiation potential of circulating primitive JAK2V617F+ stem cells from primary myelofibrosis patients is assessed. Primitive stem cells were isolated from peripheral blood of 25 patients. All patients participating in the study were diagnosed with primary myelofibrosis, have been untreated, and were found positive for JAK2V617F mutation. Isolated stem cells were analysed for purity and assessed for the expression of markers characteristic for the hemangioblast phenotype (CD34, CD133, CD45, VEGFR2, VE-Cadherin, E-Cadherin, CD31) with flow cytometry. Genomic DNA was isolated from various stem cell populations to determine the mutational status by PCR. Our results indicate that long term repopulating stem cells circulating in peripheral blood bear the JAK2V617F mutation. Hemangioblast resembling populations within the isolated prime stem cells were also found positive for the mutation. Long term repopulating stem cells bearing different allele burden for JAK2V617F mutation from PMF patient peripheral blood were expanded for up to 4 months. Various colonies formed after seeding in semisolid media were characterised by morphological features (CFU-GEMM, CFU-GM, CFU-E, CFU-M, CFU-Endo) and expressing genes by quantitative PCR. Moreover, allele burden determination for various progenitors of both hematopoietic and endothelial lineages was performed. JAK2V617F allele burden varied within individual progeny phenotypes, indicating the acquisition of the mutation that boosts the outgrowth of the malignant clone within the hemangioblast compartment of the bone marrow. Endothelial and macrophage progenitors appear heterozygotic while all rest progenitors of various hematopoietic lineages can be either heterozygotic or homozygotic. This indicates high genomic instability of the JAK2V617F+ malignant clone as it is driven into hematopoietic differentiation. Our results indicate the existence of a malignant clone with hemangioblast phenotype in PMF which can differentiate into hematopoietic and/or endothelial progenitors in vitro. Our experiments shed light to the pathogenesis of PMF by characterising the potential of the defective stem cell subpopulation responsible for the disease. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Hematopoietic Stem Cell Purification Leads to Loss of a Stem Cell Population within the Lineage Positive Cellular Fraction

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4756-4756
Author(s):  
Laura R. Goldberg ◽  
Mark Dooner ◽  
Elaine Papa ◽  
Mandy Pereira ◽  
Del Tatto Michael ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Peripheral Blood ◽  
Stem Cell Marker ◽  
Stem Cell Population ◽  
Cell Potential ◽  
Hematopoietic Stem ◽  
Stem Cell Potential

Abstract Background: Hematopoietic stem cells (HSCs) have tremendous self-renewal and differentiation capacity. The majority of murine hematopoietic stem cell studies have focused on rare purified populations of HSCs, conventionally described as negative for lineage-specific markers and positive for particular cell surface epitope profiles, including c-Kit, Sca-1, and CD150. However, our data indicate that such purifications lead to the loss of a significant population of actively cycling marrow cells with long-term multi-lineage stem cell potential. In the studies presented here, we tested the hypothesis that this discarded stem cell population lies, in part, within the lineage positive (Lin+) fraction of marrow. Methods: We flushed whole bone marrow (WBM) from B6.SJL mice and incubated it with allophycocyanin-tagged antibodies against erythroid (TER119), myeloid (CD11b, GR1), B-lymphoid (B220), or T-lymphoid (CD3, CD4, CD8) markers. Different doses of each specific Lin+ subset isolated by fluorescence activated cell sorting were competitively engrafted into lethally irradiated C57BL/6 host mice. At 1,3, and 6 months post-transplant, peripheral blood was analyzed for donor contribution to chimerism and lineage specificity. Results: Although typically considered to be without stem cell activity, we found that all Lin+ sub-fractions upon single sorting were able to contribute to marrow repopulation in competitive bone marrow transplants. For example, when lethally irradiated recipient mice received 3x105 C57BL/6J competitive whole bone marrow cells in combination with single-sorted GR1+ ± CD11b+ cells (2x106 cells/mouse), peripheral blood showed 15% donor chimerism at 6 months. Similarly, if single sorted CD3+ ±CD4+ ±CD8+ cells (70,000 cells/mouse), B220+ cells (1x106 cells/mouse), or Ter119+ cells (1x106 cells/mouse) were competitively engrafted with 3x105 C57BL/6 WBM cells, the donor Lin+ sub-fractions contributed to 2%, 15%, and 35% peripheral blood chimerism at 6 months post-transplant, respectively. This contribution was multi-lineage in all cases. When we performed double sorting of the Lin+ subsets, there was a dramatically reduced engraftment capacity between 1-6% donor chimerism for all subgroups. However, we do not think the loss of stem cell capacity with double sorting seen in these studies is due merely to the loss of classical hematopoietic stem cells (Lineage-/stem cell marker+). In our earlier studies, we showed that the total Lin+ population contains long-term multi-lineage engraftment capacity due almost entirely to actively cycling cells. Therefore, if the engraftment capacity within the single sorted Lin+ sub-fractions was due solely to the presence of classical HSCs lost with double sorting, the engraftment capacity found within the Lin+ compartment should be due only to quiescent cells in keeping with the cell cycle status of engrafting highly purified stem cells. Conclusions: Based on these data, we predict that a cycling population of stem cells exists within this single sorted, Lin+ enriched fraction discarded with conventional HSC purification. Future studies are ongoing to further characterize the subsets of Lin+ cells that both remain Lin+ and are found to be Lin- upon double sorting. We will analyze these populations for engraftment capacity, concomitant stem cell marker expression and cell cycle status, in order to fully characterize the total stem cell potential within whole bone marrow that is not included in the purified HSC populations. Disclosures No relevant conflicts of interest to declare.

scholarly journals Phenotypic and Functional Changes Induced at the Clonal Level in Hematopoietic Stem Cells After 5-Fluorouracil Treatment

Blood ◽  
1997 ◽  
Vol 89 (10) ◽  
pp. 3596-3606 ◽  
Author(s):  
Troy D. Randall ◽  
Irving L. Weissman
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Cell Population ◽  
Stem Cell Population ◽  
Normal Bone Marrow ◽  
Hematopoietic Stem ◽  
Normal Bone

Abstract A significant fraction of hematopoietic stem cells (HSCs) have been shown to be resistant to the effects of cytotoxic agents such as 5-fluorouracil (5-FU), which is thought to eliminate many of the rapidly dividing, more committed progenitors in the bone marrow and to provide a relatively enriched population of the most primitive hematopoietic progenitor cells. Although differences between 5-FU–enriched progenitor populations and those from normal bone marrow have been described, it remained unclear if these differences reflected characteristics of the most primitive stem cells that were revealed by 5-FU, or if there were changes in the stem-cell population itself. Here, we have examined some of the properties of the stem cells in the bone marrow before and after 5-FU treatment and have defined several activation-related changes in the stem-cell population. We found that long-term reconstituting stem cells decrease their expression of the growth factor receptor c-kit by 10-fold and increase their expression of the integrin Mac-1 (CD11b). These changes begin as early as 24 hours after 5-FU treatment and are most pronounced within 2 to 3 days. This activated phenotype of HSCs isolated from 5-FU–treated mice is similar to the phenotype of stem cells found in the fetal liver and to the phenotype of transiently repopulating progenitors in normal bone marrow. We found that cell cycle is induced concomitantly with these physical changes, and within 2 days as many as 29% of the stem-cell population is in the S/G2/M phases of the cell cycle. Furthermore, when examined at a clonal level, we found that 5-FU did not appear to eliminate many of the transient, multipotent progenitors from the bone marrow that were found to be copurified with long-term repopulating, activated stem cells. These results demonstrate the sensitivity of the hematopoietic system to changes in its homeostasis and correlate the expression of several important surface molecules with the activation state of HSCs.

CD133 Marks a Stem Cell Population That Drives Human Primary Myelofibrosis

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1601-1601
Author(s):  
Ioanna Triviai ◽  
Thomas Stuebig ◽  
Birte Niebuhr ◽  
Kais Hussein ◽  
Asterios Tsiftsoglou ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Population ◽  
Myeloid Cell ◽  
Primary Myelofibrosis ◽  
Jak2v617f Mutation ◽  
Stem Cell Population ◽  
Cell Populations ◽  
Cd34 Cells

Abstract Primary Myelofibrosis (PMF) is a chronic myeloproliferative neoplasm of alleged stem cell origin. To define the characteristics of malignant PMF stem cells previous studies have focused on the isolation and xenotransplantation of circulating and/or splenic, PMF patient - derived CD34+ stem/progenitor cells. Despite the reported engraftment of CD34+ cell pool, former analyses failed to reproduce major PMF parameters attributed to abnormal human myeloid cell differentiation. The focus of our work was to identify the stem cell population responsible for initiation and development of PMF. To assess the presence of malignant stem cells we analyzed peripheral blood of 30 PMF patients for expression of LT-HSC antigen CD133. To exclude committed myeloid and lymphoid circulating progenitors we performed lineage depletion of PBMCs and isolated CD133+ and/or CD34+ stem cells. Variable CD133+/CD34 ± and CD133-/CD34+ stem cell fractions from 15 PMF patients were assessed for their clonogenic potential in semisolid media and for reproduction of PMF morbidity in a xenotransplantation mouse model. JAK2V617F mutation was used as a genetic marker to track clonal evolution both in vitro and in vivo. In patients' PBMC we detected the consistent presence of a CD133+ population ranging from 0.3% to >30%, which varies in the expression of CD34. CD133 marks overlapping but also distinct cell populations as compared to CD34. To determine the differentiation potential of disparate stem cell populations, CD133+CD34+, CD133-CD34+ and CD133+CD34- cells were subfractionated from PB of 7 patients and assessed for clonogenic capacity. Strikingly, CD133+CD34+ cells exhibited multipotent, bipotent, and unipotent myeloid (including erythroid) and endothelial-like output, whereas CD133-CD34+ cells gave rise predominantly to lineage-restricted granulocyte/monocyte (GM) progenitors or endothelial-like progenitors. Thus, in contrast to circulating CD133-/CD34+ cells in PMF patients, CD133+ cells have a broader and more robust differentiation capacity to all myeloid cell types, including megakaryocyte /erythrocyte lineages. Four JAK2V617F+ patient samples were used to assess mutation burden at the single-cell level from representative colony types. Obtained results demonstrate an early acquisition of JAK2V617F mutation in the primitive CD133+ stem cell compartments, but also revealed an unexpected variability in the genotypes of emerging progenitors. Homozygous JAK2617F/617F progenitors were detectable in all analyzed patient samples, even if a relative low JAK2V617F burden (30%) was determined from the initial pool of CD133+ cells. A disproportionately high incidence of a homozygous JAK2V617F genotype was observed in erythroid progenitors, indicating a skewing for this lineage. Homozygosity was additionally detected in megakaryocytic and multipotent progenitors. In vivo xenotransplantation experiments of various subfractions confirm the origin of multipotent JAK2V617F+ progenitors from CD133+/CD34± stem cells. Transplantation of PMF patient-derived CD133+/CD34± stem cells in immuno-compromised mice induces abnormal human JAK2V617F+ erythroid, megakaryocytic, and monocytic differentiation, splenomegaly, bone marrow/splenic fibrosis and anemia, reproducing many aspects of PMF development. Our data provide the first evidence for the existence of a CD133+ LT-HSC population responsible for development of PMF. It is for the first time demonstrated that JAK2V617F mutation in PMF occurs at the level of a multipotent stem cell, from which all abnormal myeloid cells emanate during evolution of the disease. Identification of the stem cell compartment involved in the triggering and progression of PMF provides the basis to elucidate the nature of the complex niche interactions in myeloproliferative neoplasms. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Phenotypic and Functional Changes Induced at the Clonal Level in Hematopoietic Stem Cells After 5-Fluorouracil Treatment

Blood ◽  
1997 ◽  
Vol 89 (10) ◽  
pp. 3596-3606 ◽  
Author(s):  
Troy D. Randall ◽  
Irving L. Weissman
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Cell Population ◽  
Stem Cell Population ◽  
Normal Bone Marrow ◽  
Hematopoietic Stem ◽  
Normal Bone

A significant fraction of hematopoietic stem cells (HSCs) have been shown to be resistant to the effects of cytotoxic agents such as 5-fluorouracil (5-FU), which is thought to eliminate many of the rapidly dividing, more committed progenitors in the bone marrow and to provide a relatively enriched population of the most primitive hematopoietic progenitor cells. Although differences between 5-FU–enriched progenitor populations and those from normal bone marrow have been described, it remained unclear if these differences reflected characteristics of the most primitive stem cells that were revealed by 5-FU, or if there were changes in the stem-cell population itself. Here, we have examined some of the properties of the stem cells in the bone marrow before and after 5-FU treatment and have defined several activation-related changes in the stem-cell population. We found that long-term reconstituting stem cells decrease their expression of the growth factor receptor c-kit by 10-fold and increase their expression of the integrin Mac-1 (CD11b). These changes begin as early as 24 hours after 5-FU treatment and are most pronounced within 2 to 3 days. This activated phenotype of HSCs isolated from 5-FU–treated mice is similar to the phenotype of stem cells found in the fetal liver and to the phenotype of transiently repopulating progenitors in normal bone marrow. We found that cell cycle is induced concomitantly with these physical changes, and within 2 days as many as 29% of the stem-cell population is in the S/G2/M phases of the cell cycle. Furthermore, when examined at a clonal level, we found that 5-FU did not appear to eliminate many of the transient, multipotent progenitors from the bone marrow that were found to be copurified with long-term repopulating, activated stem cells. These results demonstrate the sensitivity of the hematopoietic system to changes in its homeostasis and correlate the expression of several important surface molecules with the activation state of HSCs.

scholarly journals Long-term repopulation of irradiated mice with limiting numbers of purified hematopoietic stem cells: in vivo expansion of stem cell phenotype but not function

Blood ◽  
1995 ◽  
Vol 85 (4) ◽  
pp. 1006-1016 ◽  
Author(s):  
GJ Spangrude ◽  
DM Brooks ◽  
DB Tumas
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Cell Surface ◽  
Hematopoietic Stem Cells ◽  
Peripheral Blood ◽  
Antigen Expression ◽  
Hematopoietic Stem ◽  
Surface Antigen Expression

Hematopoietic stem cells were isolated from normal adult mouse bone marrow based on surface antigen expression (Thy-1.1(low)Lin(neg)Ly- 6A/E+) and further selected for low retention of rhodamine 123. This population of cells (Rh-123low) could mediate radioprotection and long- term (greater than 12 months) repopulation after transplantation of as few as 25 cells. Transfer of five genetically marked Rh-123low cells in the presence of 10(5) normal bone marrow cells resulted in reconstitution of peripheral blood by greater than 10% donor cells in 64% (30 of 47) of recipient mice. Of 46 animals surviving after 24 weeks, 10 had over 50% donor-derived cells in peripheral blood. Two general patterns of long-term reconstitution were observed: one in which many donor-derived cells were observed 5 to 6 weeks after reconstitution and another in which donor-derived cells were rare initially but expanded with time. This result suggests that two classes of long-term repopulating hematopoietic stem cells exist, differing in their ability to function early in the course of transplantation. Alternatively, distinct anatomic sites of engraftment may dictate these two outcomes from a single type of cell. As an approach to measure the extent of self-renewal by the injected cells, recipients of five or 200 stem cells were killed 8 to 13 months after the transplants, and Thy- 1.1(low)Lin(neg)Ly-6A/E+ progeny of the original injected cells were isolated for a second transplant. While a numerical expansion of cells expressing the cell surface phenotype of stem cells was observed, along with activity in the colony-forming unit-spleen assay, the expanded cells were vastly inferior in radioprotection and long-term reconstitution assays when compared with cells freshly isolated from normal animals. This result demonstrates that in stem cell expansion experiments, cell surface antigen expression is not an appropriate indicator of stem cell function.

Abstract 239: Stem Cell Therapy Improves Critical Limb Ischemia

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Alaa Marzouk
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Embryonic Stem ◽  
Limb Ischemia ◽  
Control Group ◽  
Chronic Limb Ischemia

Introduction: The journey from single cell to complex being is attributable to stem cells role. Adult stem cells originate during ontogeny & persist in specialized niches within organs. Asymmetric division of each stem cell during differentiation produces : one daughter stem cell & one daughter transit amplifying/intermediate cell having migratory properties. Forced migration of hematopoietic stem/progenitor cells (HSPC) from bone marrow into peripheral blood is called mobilization. Accumulating evidence suggests that attenuation of the chemokine stromal derived factor-1(SDF-1)-CXCR4 axis that plays a pivotal role in retention of HSPC in bone marrow (BM) results in the release of these cells from the BM into peripheral blood. Recently, adult cells have been genetically reprogrammed to an embryonic stem cell like state. Induced pluripotent stem cells (IPSCs) were similar to human embryonic stem cells in morphology, proliferative capacity, expression of cell surface antigens, & gene expression. Treatment of ischemic vascular disease of lower limbs remains a significant challenge. Unfortunately, if medical & surgical salvage procedures fail, amputation is an unavoidable result for those patients. Aim of Work: (Hypothesis) To assess the application of implantation of autologous stem/progenitor cell in the treatment of chronic limb ischemia & to evaluate the safety, efficacy & feasibility of this novel therapeutic approach. Methods: A total of 24 patients with chronic limb ischemia not eligible for arterial reconstruction or endovascular procedures were enrolled & randomized (1:1) to either the implanted group or the control group. Control group: Conventional medical therapy in the form of anti platelet therapy & vasodilators. Implanted group: Subcutaneous injection of 300μ g/day of recombinant human granulocyte colony stimulating factor (G-CSF) for 5 days to mobilize stem/progenitor cells from BM. Total leucocytic count is measured daily to follow up successful mobilization of bone marrow mononuclear cells (BMMNCs). Stem cell Harvesting After 5 days peripheral blood mononuclear cells (PBMNCs) were harvested using a cell separator. Samples from apheresis products are subjected to TLC measurement & immunophenotypic characterization of CD34+ cells by flow cytometry. The collected PBMNCs were implanted by multiple intramuscular injections into ischemic limbs. Results: There was significant increase in pain free walking distance & ankle/brachial index (ABI) & significant decreased rest pain. Effectiveness was documented by : reduced number of amputation, increase ABI & improvement of the quality of life in therapeutic group compared to control group. Conclusion: The novel therapeutic approach of PBMNCs implantation in patients with chronic limb ischemia is safe, feasible & effective in decreasing co-morbidity & rate of amputation. Safety was manifested by absence of complications during G-CSF therapy or during harvesting & injection of the stem cells. Recommendations: 1- Future studies on larger number of patients & longer follow up. 2- Controlled studies using different methods & different cell population (PBMNCs, BMMNCs or MSCs) to compare the outcome of each. 3-Studing the role of endothelial progenitor cell dysfunction in different ischemic diseases to develop successful gene therapy.

Growth factor treatment prior to low-dose total body irradiation increases donor cell engraftment after bone marrow transplantation in mice

Blood ◽  
2002 ◽  
Vol 100 (1) ◽  
pp. 312-317 ◽  
Author(s):  
Estelle J. K. Noach ◽  
Albertina Ausema ◽  
Jan H. Dillingh ◽  
Bert Dontje ◽  
Ellen Weersing ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Growth Factors ◽  
Low Dose ◽  
Donor Cell ◽  
Hematopoietic Growth Factors ◽  
Cell Engraftment ◽  
Total Body

Abstract Low-toxicity conditioning regimens prior to bone marrow transplantation (BMT) are widely explored. We developed a new protocol using hematopoietic growth factors prior to low-dose total body irradiation (TBI) in recipients of autologous transplants to establish high levels of long-term donor cell engraftment. We hypothesized that treatment of recipient mice with growth factors would selectively deplete stem cells, resulting in successful long-term donor cell engraftment after transplantation. Recipient mice were treated for 1 or 7 days with growth factors (stem cell factor [SCF] plus interleukin 11 [IL-11], SCF plus Flt-3 ligand [FL], or granulocyte colony-stimulating factor [G-CSF]) prior to low-dose TBI (4 Gy). Donor cell chimerism was measured after transplantation of congenic bone marrow cells. High levels of donor cell engraftment were observed in recipients pretreated for 7 days with SCF plus IL-11 or SCF plus FL. Although 1-day pretreatments with these cytokines initially resulted in reduced donor cell engraftment, a continuous increase in time was observed, finally resulting in highly significantly increased levels of donor cell contribution. In contrast, G-CSF treatment showed no beneficial effects on long-term engraftment. In vitro stem cell assays demonstrated the effect of cytokine treatment on stem cell numbers. Donor cell engraftment and number of remaining recipient stem cells after TBI were strongly inversely correlated, except for groups treated for 1 day with SCF plus IL-11 or SCF plus FL. We conclude that long-term donor cell engraftment can be strongly augmented by treatment of recipient mice prior to low-dose TBI with hematopoietic growth factors that act on primitive cells.

scholarly journals Mobilization of long-term reconstituting hematopoietic stem cells in mice by recombinant human interleukin 7.

1995 ◽  
Vol 181 (1) ◽  
pp. 369-374 ◽  
Author(s):  
K J Grzegorzewski ◽  
K L Komschlies ◽  
S E Jacobsen ◽  
F W Ruscetti ◽  
J R Keller ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Peripheral Blood ◽  
Peripheral Blood Leukocytes ◽  
Gene Modification ◽  
Blood Leukocytes ◽  
Hematopoietic Stem ◽  
Interleukin 7 ◽  
Cell Repopulation

Administration of recombinant human interleukin 7 (rh)IL-7 to mice has been reported by our group to increase the exportation of myeloid progenitors (colony-forming unit [CFU]-c and CFU-granulocyte erythroid megakarocyte macrophage) from the bone marrow to peripheral organs (blood, spleen[s], and liver). We now report that IL-7 also stimulates a sixfold increase in the number of more primitive CFU-S day 8 (CFU-S8) and day 12 (CFU-S12) in the peripheral blood leukocytes (PBL) of mice treated with rhIL-7 for 7 d. Moreover, > 90% of lethally irradiated recipient mice that received PBL from rhIL-7-treated donor mice have survived for > 6 mo whereas none of the recipient mice that received an equal number of PBL from diluent-treated donors survived. Flow cytometry analysis at 3 and 6 mo after transplantation revealed complete trilineage (T, B, and myelomonocytic cell) repopulation of bone marrow, thymus, and spleen by blood-borne stem/progenitor cells obtained from rhIL-7-treated donor mice. Thus, IL-7 may prove valuable for mobilizing pluripotent stem cells with long-term repopulating activity from the bone marrow to the peripheral blood for the purpose of gene modification and/or autologous or allogeneic stem cell transplantation.

scholarly journals Self-repopulating recipient bone marrow resident macrophages promote long-term hematopoietic stem cell engraftment

Blood ◽  
2018 ◽  
Vol 132 (7) ◽  
pp. 735-749 ◽  
Author(s):  
Simranpreet Kaur ◽  
Liza J. Raggatt ◽  
Susan M. Millard ◽  
Andy C. Wu ◽  
Lena Batoon ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Hematopoietic Stem ◽  
Cell Engraftment ◽  
Key Points ◽  
Bone Marrow Engraftment

Key Points Recipient macrophages persist in hematopoietic tissues and self-repopulate via in situ proliferation after syngeneic transplantation. Targeted depletion of recipient CD169+ macrophages after transplant impaired long-term bone marrow engraftment of hematopoietic stem cells.

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