scholarly journals Inhibition of SGLT-2 rescues bone marrow cell traffic for vascular repair. Role of glucose control and ketogenesis

2021 ◽  
Author(s):  
Mattia Albiero ◽  
Serena Tedesco ◽  
Francesco Ivan Amendolagine ◽  
Marianna D’Anna ◽  
Ludovica Migliozzi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Marrow Cell ◽  
Vascular Protection ◽  
Cxcr4 Antagonist ◽  
Vascular Effect ◽  
Hematopoietic Stem ◽  
Glucose Levels ◽  
Circulating Cells ◽  
Endothelial Repair ◽  
Cell Mobilization

The mechanisms whereby sodium-glucose cotransporter-2 inhibitors (SGLT2i) improve cardiovascular outcomes in people with diabetes are incompletely understood. Recent studies show that SGLT2i may increase the levels of circulating cells with vascular regenerative capacity, at least in part by lowering glycemia. Here, we used mice with streptozotocin-induced diabetes treated with the SGLT2i dapagliflozin at a dose that reduced glucose levels by ~20%. Dapagliflozin improved the diabetes-associated defect of hematopoietic stem cell mobilization after stimulation with G-CSF. Dapagliflozin rescued the traffic of bone marrow (BM)-derived cells to injured carotid arteries and improved endothelial healing in diabetic mice. Defective homing of CD49d<sup>+</sup> granulocytes was causally linked with impaired endothelial repair and was reversed by dapagliflozin. The effects of dapagliflozin were mimicked by a similar extent of glucose reduction achieved with insulin therapy, and by a ketone drink that artificially elevated β-hydroxybutyrate. Inhibition of endothelial repair by resident cells using the CXCR4 antagonist AMD3100 did not abolish the vascular effect of dapagliflozin, indirectly supporting that endothelial healing by dapagliflozin was mediated by recruitment of circulating cells. In summary, we show that dapagliflozin improved the traffic of BM-derived hematopoietic cells to the site of vascular injury, providing a hitherto unappreciated mechanism of vascular protection.

scholarly journals Inhibition of SGLT-2 rescues bone marrow cell traffic for vascular repair. Role of glucose control and ketogenesis

2021 ◽  
Author(s):  
Mattia Albiero ◽  
Serena Tedesco ◽  
Francesco Ivan Amendolagine ◽  
Marianna D’Anna ◽  
Ludovica Migliozzi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Marrow Cell ◽  
Vascular Protection ◽  
Cxcr4 Antagonist ◽  
Vascular Effect ◽  
Hematopoietic Stem ◽  
Glucose Levels ◽  
Circulating Cells ◽  
Endothelial Repair ◽  
Cell Mobilization

The mechanisms whereby sodium-glucose cotransporter-2 inhibitors (SGLT2i) improve cardiovascular outcomes in people with diabetes are incompletely understood. Recent studies show that SGLT2i may increase the levels of circulating cells with vascular regenerative capacity, at least in part by lowering glycemia. Here, we used mice with streptozotocin-induced diabetes treated with the SGLT2i dapagliflozin at a dose that reduced glucose levels by ~20%. Dapagliflozin improved the diabetes-associated defect of hematopoietic stem cell mobilization after stimulation with G-CSF. Dapagliflozin rescued the traffic of bone marrow (BM)-derived cells to injured carotid arteries and improved endothelial healing in diabetic mice. Defective homing of CD49d<sup>+</sup> granulocytes was causally linked with impaired endothelial repair and was reversed by dapagliflozin. The effects of dapagliflozin were mimicked by a similar extent of glucose reduction achieved with insulin therapy, and by a ketone drink that artificially elevated β-hydroxybutyrate. Inhibition of endothelial repair by resident cells using the CXCR4 antagonist AMD3100 did not abolish the vascular effect of dapagliflozin, indirectly supporting that endothelial healing by dapagliflozin was mediated by recruitment of circulating cells. In summary, we show that dapagliflozin improved the traffic of BM-derived hematopoietic cells to the site of vascular injury, providing a hitherto unappreciated mechanism of vascular protection.

ALL Cells Mobilized by AMD3100 Are More Proliferative, and Remain In the Circulation Longer Than Normal HSC, Enhancing the Action of Vincristine

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2137-2137 ◽  
Author(s):  
Linda J. Bendall ◽  
Robert Welschinger ◽  
Florian Liedtke ◽  
Carole Ford ◽  
Aileen Dela Pena ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Peripheral Blood ◽  
Bone Marrow Microenvironment ◽  
Hematopoietic Progenitors ◽  
Cxcr4 Antagonist ◽  
Hematopoietic Stem ◽  
Stem And Progenitor Cells ◽  
Cell Mobilization ◽  
Cycle Dependent

Abstract Abstract 2137 The chemokine CXCL12, and its receptor CXCR4, play an essential role in homing and engraftment of normal hematopoietic cells in the bone marrow, with the CXCR4 antagonist AMD3100 inducing the rapid mobilization of hematopoietic stem and progenitor cells into the blood in mice and humans. We have previously demonstrated that AMD3100 similarly induces the mobilization of acute lymphoblastic leukemia (ALL) cells into the peripheral blood. The bone marrow microenvironment is thought to provide a protective niche for ALL cells, contributing to chemo-resistance. As a result, compounds that disrupt leukemic cell interactions with the bone marrow microenvironment are of interest as chemo-sensitizing agents. However, the mobilization of normal hematopoietic stem and progenitor cells may also increase bone marrow toxicity. To better evaluate how such mobilizing agents affect normal hematopoietic progenitors and ALL cells, the temporal response of ALL cells to the CXCR4 antagonist AMD3100 was compared to that of normal hematopoietic progenitor cells using a NOD/SCID xenograft model of ALL and BALB/c mice respectively. ALL cells from all 7 pre-B ALL xenografts were mobilized into the peripheral blood by AMD3100. Mobilization was apparent 1 hour and maximal 3 hours after drug administration, similar to that observed for normal hematopoietic progenitors. However, ALL cells remained in the circulation for longer than normal hematopoietic progenitors. The number of ALL cells in the circulation remained significantly elevated in 6 of 7 xenografts examined, 6 hours post AMD3100 administration, a time point by which circulating normal hematopoietic progenitor levels had returned to baseline. No correlation between the expression of the chemokine receptor CXCR4 or the adhesion molecules VLA-4, VLA-5 or CD44, and the extent or duration of ALL cell mobilization was detected. In contrast, the overall motility of the ALL cells in chemotaxis assays was predictive of the extent of ALL cell mobilization. This was not due to CXCL12-specific chemotaxis because the association was lost when correction for background motility was undertaken. In addition, AMD3100 increased the proportion of actively cells ALL cells in the peripheral blood. This did not appear to be due to selective mobilization of cycling cells but reflected the more proliferative nature of bone marrow as compared to peripheral blood ALL cells. This is in contrast to the selective mobilization of quiescent normal hematopoietic stem and progenitor cells by AMD3100. Consistent with these findings, the addition of AMD3100 to the cell cycle dependent drug vincristine, increased the efficacy of this agent in NOD/SCID mice engrafted with ALL. Overall, this suggests that ALL cells will be more sensitive to effects of agents that disrupt interactions with the bone marrow microenvironment than normal progenitors, and that combining agents that disrupt ALL retention in the bone marrow may increase the therapeutic effect of cell cycle dependent chemotherapeutic agents. Disclosures: Bendall: Genzyme: Honoraria.

Rapid Mobilization of Murine Hematopoietic Stem and Progenitor Cells with TG-0054, a Novel CXCR4 Antagonist.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3542-3542 ◽  
Author(s):  
Ying-Huey Huang ◽  
Yi-Chun Liu ◽  
Chi-Feng Yen ◽  
Hua-Chien Chen ◽  
Shu-Jen Chen ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Chemokine Receptors ◽  
Synergistic Effects ◽  
Stem Cell Mobilization ◽  
Cxcr4 Antagonist ◽  
Hematopoietic Stem ◽  
Cxcr4 Receptor ◽  
Cell Mobilization

Abstract Abstract 3542 Poster Board III-479 Background The interaction between SDF-1 and its receptor, CXCR4, is responsible for retaining of stem cells in the bone marrow. CXCR4 antagonist disrupts the SDF-1/CXCR4 interaction and mobilizes CD34+ hematopoietic stem cells (CD34+ HSCs) and CD133+ endothelial progenitor cells (CD133+ EPCs) from bone marrow into circulation, which can be used as a source for stem cell transplantation and other potential clinical indications. TG-0054 is a novel CXCR4 antagonist. In vitro CXCR4 antagonistic activity and in vivo stem cell mobilization activity of TG-0054 were determined in this study. Materials and Methods In vitro pharmacological assays, including GTP-binding assay, calcium mobilization assay, and chemotaxis assays, were performed to assess the potency of TG-0054 as a CXCR4 antagonist. In addition, receptor-binding assays against a panel of human chemokine receptors as well as other 68 cellular receptors were screened to evaluate the specificity of TG-0054. Kinetics and dose-dependent response of stem cell mobilization by TG-0054 were demonstrated in BALB/c mice. Activity of stem cell mobilization of TG-0054 when used alone or combined with G-CSF was also studied. Results TG-0054 blocked SDF-1-binding to CXCR4 receptor with an IC50 of 10 nM and inhibited SDF-1–induced GTP-binding (IC50 = 6 nM), chemotaxis (IC50 = 43 nM), and calcium mobilization (IC50 = 59 nM). TG-0054 showed greater than 3000-fold selectivity for CXCR4 receptor over other chemokine receptors. It is noteworthy that the IC50 for the inhibitory effect of TG-0054 on hERG potassium currents was greater than 1000 μM when human embryonic kidney (HEK) cells were used to examine the in vitro effects on the hERG potassium channel currents. In animal studies, TG-0054 rapidly and effectively mobilized CD34+ HSCs and CD133+ EPCs into circulation. Single intravenous (IV) administration of TG-0054 resulted in a rapid increase of total white blood cell (WBC) counts, as well as CXCR4+, CD34+, and CD133+ cells in peripheral blood between 1–3 hour post-injection and the cell counts returned to baseline within 6 hours. At their maximum tolerated doses (MTD), TG-0054 increased CXCR4+ cells by 28.7-fold in mice. Furthermore, TG-0054 efficiently mobilized CD34+ (14.5-fold) and CD133+ (7.9-fold) cells. The combined effects of TG-0054 and G-CSF on HSCs and EPCs mobilization from the bone marrow in mice were also investigated. G-CSF (100 μg/kg/day) was administered subcutaneously (SC) from Day 1 to Day 4 followed by a single IV injection of TG-0054 or AMD3100 on Day 5. Synergistic effects were observed in all cell types in mice receiving combination of G-CSF and 50 mg/kg of TG-0054 (total WBC 23.0-fold, CXCR4+ 29.0-fold, CD34+ 37.1-fold, CD133+ 110.8-fold of increase in combination group). Conclusion It was concluded that TG-0054 was a potent and selective CXCR4 antagonist intended for the use of stem cell transplant and other clinical indications. It showed strong stem cell mobilization activity comparable to G-CSF when used alone, and demonstrated synergistic effects when combined with G-CSF in a nonclinical model. Disclosures: Huang: TaiGen Biotechnology Inc.: Employment. Liu:TaiGen Biotechnology Inc.: Employment. Yen:TaiGen Biotechnology Inc.: Employment. Chen:TaiGen Biotechnology Inc.: Consultancy. Chen:TaiGen Biotechnology Inc.: Consultancy. King:TaiGen Biotechnology Inc.: Employment. Hsu:TaiGen Biotechnology, Inc.: Membership on an entity's Board of Directors or advisory committees.

scholarly journals Focus on Osteosclerotic Progression in Primary Myelofibrosis

Biomolecules ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 122
Author(s):  
Mariarita Spampinato ◽  
Cesarina Giallongo ◽  
Alessandra Romano ◽  
Lucia Longhitano ◽  
Enrico La Spina ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Marrow Cell ◽  
Myeloproliferative Neoplasm ◽  
Primary Myelofibrosis ◽  
Hematopoietic Stem ◽  
Clonal Proliferation ◽  
Cytokines And Chemokines ◽  
Bone Damage ◽  
Underlying Mechanisms ◽  
Modulating Functions

Primary myelofibrosis (PMF) is a myeloproliferative neoplasm characterized by hematopoietic stem-cell-derived clonal proliferation, leading to bone marrow (BM) fibrosis. Hematopoiesis alterations are closely associated with modifications of the BM microenvironment, characterized by defective interactions between vascular and endosteal niches. As such, neoangiogenesis, megakaryocytes hyperplasia and extensive bone marrow fibrosis, followed by osteosclerosis and bone damage, are the most relevant consequences of PMF. Moreover, bone tissue deposition, together with progressive fibrosis, represents crucial mechanisms of disabilities in patients. Although the underlying mechanisms of bone damage observed in PMF are still unclear, the involvement of cytokines, growth factors and bone marrow microenvironment resident cells have been linked to disease progression. Herein, we focused on the role of megakaryocytes and their alterations, associated with cytokines and chemokines release, in modulating functions of most of the bone marrow cell populations and in creating a complex network where impaired signaling strongly contributes to progression and disabilities.

scholarly journals CD34+ human marrow cells that express low levels of Kit protein are enriched for long-term marrow-engrafting cells

Blood ◽  
1996 ◽  
Vol 87 (10) ◽  
pp. 4136-4142 ◽  
Author(s):  
I Kawashima ◽  
ED Zanjani ◽  
G Almaida-Porada ◽  
AW Flake ◽  
H Zeng ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Marrow Cell ◽  
In Utero ◽  
Fetal Sheep ◽  
Hematopoietic Stem ◽  
Show Evidence ◽  
Marrow Cells

Using in utero transplantation into fetal sheep, we examined the capability of human bone marrow CD34+ cells fractionated based on Kit protein expression to provide long-term in vivo engraftment. Twelve hundred to 5,000 CD34+ Kit-, CD34+ Kit(low), and CD34+ Kit(high) cells were injected into a total of 14 preimmune fetal sheep recipients using the amniotic bubble technique. Six fetuses were killed in utero 1.5 months after bone marrow cell transplantation. Two fetuses receiving CD34+ Kit(low) cells showed signs of engraftment according to analysis of CD45+ cells in their bone marrow cells and karyotype studies of the colonies grown in methylcellulose culture. In contrast, two fetuses receiving CD34+ Kit(high) cells and two fetuses receiving CD34+ Kit- cells failed to show evidence of significant engraftment. Two fetuses were absorbed. A total of six fetuses receiving different cell populations were allowed to proceed to term, and the newborn sheep were serially examined for the presence of chimerism. Again, only the two sheep receiving CD34+ Kit(low) cells exhibited signs of engraftment upon serial examination. Earlier in studies of murine hematopoiesis, we have shown stage-specific changes in Kit expression by the progenitors. The studies of human cells reported here are in agreement with observations in mice, and indicate that human hematopoietic stem cells are enriched in the Kit(low) population.

Abstract 4020: The Novel TrkB Agonist, 7,8-Dihydroxyflavone Enhances Stem Cell Mobilization After Stroke.

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
J Mocco ◽  
Aqeela Afzal ◽  
Nagheme Thomas ◽  
Zuha Warraich ◽  
Jeffery Kleim
Keyword(s):  
Bone Marrow ◽  
Mononuclear Cells ◽  
Critical Role ◽  
Stroke Recovery ◽  
The Novel ◽  
Hematopoietic Stem ◽  
Post Surgery ◽  
Cell Mobilization ◽  
Neurotropic Factor ◽  
Oxidative Effects

Background: Increasing levels of circulating Hematopoietic Stem Cells (HSC)/Hematopoietic Progenitor Cells (HPC), bone marrow derived mononuclear cells that promote repair in areas of injury, have been demonstrated to correlate with improved neurological function following stroke, suggesting a potentially critical role for HSC/HPC’s in limiting stroke injury and/or facilitating stroke recovery. Flavonoids, found in plants and fruit, exert anti-oxidative effects. Recent studies have demonstrated that 7,8 Dihydroxyflavone (DHF) is a potent TrkB agonist mimicking Brain Derived Neurotropic Factor, thus making it a powerful potential tool for treating neurological disorders. Stromal Derived Growth Factor 1-Alpha (SDF1-A) along with its receptor CXCR4 is a potent chemo attractant released by areas of injury. SDF1-A has been shown to mobilize HSC/HPC from the bone marrow to the blood and lead to ‘homing’ of the cells to an area of injury. We investigated the effect of DHF on HSC/HPC function following cerebral ischemia. Methods: Ischemic damage was induced in adult male Long Evans hooded rats (350-400g) with a peri-MCA injection of the vasoconstriction peptide ET-1. The rats were sacrificed at 24 hours post surgery and their bone marrow and blood HSC/HPC enriched using nanoparticles tagged with LIN negative and CD90 markers. Results: Stroked animals showed an increase in bone marrow production of HSC/HPC versus control animals (31.9±7 versus 2±0.5, p<0.05). The mobilization of the HSC/HPC from the bone marrow to the blood was also significantly higher in the stroked animals versus control animals (43±19 versus 3.6±0.3, p<0.05). Following stroke, DHF pre-treated HSC/HPC’s demonstrated significantly improved migration along an SDF-1 gradient compared to controls (129±1.0 versus 108±1.15, p<0.05), despite the fact that DHF alone provided no independent migratory stimulus. Conclusions: The results suggest that DHF may be a viable compound to facilitate HSC/HPC migration post-stroke.

scholarly journals Albumin Modifies Responses to Hematopoietic Stem Cell Mobilizing Agents in Mice

Cells ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 4 ◽  
Author(s):  
Eva Danner ◽  
Halvard Bonig ◽  
Eliza Wiercinska
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Wild Type ◽  
Cxcr4 Antagonist ◽  
Hematopoietic Stem ◽  
Split Dose ◽  
Healthy Donors ◽  
Hematopoietic Stem Cell Mobilization ◽  
Csf Levels ◽  
Cell Mobilization

Albumin, the most abundant plasma protein, not only controls osmotic blood pressure, but also serves as a carrier for various small molecules, including pharmaceuticals. Its impact on pharmacological properties of many drugs has been extensively studied over decades. Here, we focus on its interaction with the following mobilizing agents: Granulocyte-colony stimulating factor (G-CSF) and AMD3100, where such analyses are lacking. These compounds are widely used for hematopoietic stem cell mobilization of healthy donors or patients. Using albumin-deficient (Alb−/−) mice, we studied the contribution of albumin to mobilization outcomes. Mobilization with the bicyclam CXCR4 antagonist AMD3100 was attenuated in Alb−/− mice compared to wild-type littermates. By contrast, mobilization with recombinant human G-CSF (rhG-CSF), administered twice daily over a five-day course, was significantly increased in Alb−/− mice. In terms of a mechanism, we show that rhG-CSF bioavailability in the bone marrow is significantly improved in Alb−/− mice, compared to wild-type (WT) littermates, where rhG-CSF levels dramatically drop within a few hours of the injection. These observations likely explain the favorable mobilization outcomes with split-dose versus single-dose administration of rhG-CSF to healthy donors.

Sphingosine-1-phosphate facilitates trafficking of hematopoietic stem cells and their mobilization by CXCR4 antagonists in mice

Blood ◽  
2012 ◽  
Vol 119 (3) ◽  
pp. 707-716 ◽  
Author(s):  
Julius G. Juarez ◽  
Nadia Harun ◽  
Marilyn Thien ◽  
Robert Welschinger ◽  
Rana Baraz ◽  
...  
Keyword(s):  
Stem Cells ◽  
Steady State ◽  
Hematopoietic Stem Cells ◽  
Progenitor Cell ◽  
Hematopoietic Progenitors ◽  
Cxcr4 Antagonist ◽  
Hematopoietic Stem ◽  
Sphingosine 1 Phosphate ◽  
Cxcr4 Antagonists ◽  
Cell Mobilization

Abstract CXCL12 and VCAM1 retain hematopoietic stem cells (HSCs) in the BM, but the factors mediating HSC egress from the BM to the blood are not known. The sphingosine-1-phosphate receptor 1 (S1P1) is expressed on HSCs, and S1P facilitates the egress of committed hematopoietic progenitors from the BM into the blood. In the present study, we show that both the S1P gradient between the BM and the blood and the expression of S1P1 are essential for optimal HSC mobilization by CXCR4 antagonists, including AMD3100, and for the trafficking of HSCs during steady-state hematopoiesis. We also demonstrate that the S1P1 agonist SEW2871 increases AMD3100-induced HSC and progenitor cell mobilization. These results suggest that the combination of a CXCR4 antagonist and a S1P1 agonist may prove to be sufficient for mobilizing HSCs in normal donors for transplantation purposes, potentially providing a single mobilization procedure and eliminating the need to expose normal donors to G-CSF with its associated side effects.

Differential Role for VLA-5 in Mobilization of Heamotopoieic Stem Cells Toward Peripheral Blood and Homing to Bone Marrow and Spleen.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2190-2190 ◽  
Author(s):  
Pieter K. Wierenga ◽  
Ellen Weersing ◽  
Bert Dontje ◽  
Gerald de Haan ◽  
Ronald P. van Os
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Progenitor Cells ◽  
Peripheral Blood ◽  
Hematopoietic Stem ◽  
Late Antigen ◽  
Cell Mobilization

Abstract Adhesion molecules have been implicated in the interactions of hematopoietic stem and progenitor cells with the bone marrow extracellular matrix and stromal cells. In this study we examined the role of very late antigen-5 (VLA-5) in the process of stem cell mobilization and homing after stem cell transplantation. In normal bone marrow (BM) from CBA/H mice 79±3 % of the cells in the lineage negative fraction express VLA-5. After mobilization with cyclophosphamide/G-CSF, the number of VLA-5 expressing cells in mobilized peripheral blood cells (MPB) decreases to 36±4%. The lineage negative fraction of MPB cells migrating in vitro towards SDF-1α (M-MPB) demonstrated a further decrease to 3±1% of VLA-5 expressing cells. These data are suggestive for a downregulation of VLA-5 on hematopoietic cells during mobilization. Next, MPB cells were labelled with PKH67-GL and transplanted in lethally irradiated recipients. Three hours after transplantation an increase in VLA-5 expressing cells was observed which remained stable until 24 hours post-transplant. When MPB cells were used the percentage PKH-67GL+ Lin− VLA-5+ cells increased from 36% to 88±4%. In the case of M-MPB cells the number increased from 3% to 33±5%. Although the increase might implicate an upregulation of VLA-5, we could not exclude selective homing of VLA-5+ cells as a possible explanation. Moreover, we determined the percentage of VLA-5 expressing cells immediately after transplantation in the peripheral blood of the recipients and were not able to observe any increase in VLA-5+ cells in the first three hours post-tranpslant. Finally, we separated the MPB cells in VLA-5+ and VLA-5− cells and plated these cells out in clonogenic assays for progenitor (CFU-GM) and stem cells (CAFC-day35). It could be demonstared that 98.8±0.5% of the progenitor cells and 99.4±0.7% of the stem cells were present in the VLA-5+ fraction. Hence, VLA-5 is not downregulated during the process of mobilization and the observed increase in VLA-5 expressing cells after transplantation is indeed caused by selective homing of VLA-5+ cells. To shed more light on the role of VLA-5 in the process of homing, BM and MPB cells were treated with an antibody to VLA-5. After VLA-5 blocking of MPB cells an inhibition of 59±7% in the homing of progenitor cells in bone marrow could be found, whereas homing of these subsets in the spleen of the recipients was only inhibited by 11±4%. For BM cells an inhibition of 60±12% in the bone marrow was observed. Homing of BM cells in the spleen was not affected at all after VLA-5 blocking. Based on these data we conclude that mobilization of hematopoietic progenitor/stem cells does not coincide with a downregulation of VLA-5. The observed increase in VLA-5 expressing cells after transplantation is caused by preferential homing of VLA-5+ cells. Homing of progenitor/stem cells to the bone marrow after transplantation apparantly requires adhesion interactions that can be inhibited by blocking VLA-5 expression. Homing to the spleen seems to be independent of VLA-5 expression. These data are indicative for different adhesive pathways in the process of homing to bone marrow or spleen.

Sign in / Sign up

Export Citation Format

Share Document