Immuno Haematological Reconstitution after T-Cell-Depleted HLA-Haploidentical Stem Cell Transplantation for Thalassemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1774-1774
Author(s):  
Antonella Isgrò ◽  
Buket Erer ◽  
Pietro Sodani ◽  
Paola Polchi ◽  
Marco Marziali ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Stem Cell ◽  
T Cell ◽  
Nk Cells ◽  
Progenitor Cells ◽  
Stromal Cells ◽  
Cd4 T Cells ◽  
Normal Subjects

Abstract Background. We evaluated haematological and immunological characteristics of four thalassemia patients after T-cell-depleted HLA-haploidentical stem cell transplantation Methods. We evaluated the clonogenic capability by the colony forming cell assay (CFC) and the long term culture-initiating cell (LTC-IC) assay at baseline and 20 days after transplant. Stromal cells were obtained from long term culture of bone marrow mononuclear cells (BMMCs) and analysed by immunohystochemistry. Lymphocyte subsets were studied by flow cytometry; and stromal IL-7 production by BMMCs was analysed by ELISA. Results. At baseline, no significant differences were observed in haematological and in immunological parameters in thalassemia patients when compared with a group of normal subjects Day + 20 after transplant, a reduced clonogenic capability was observed (4 ± 2 vs. 41 ± 40 CFU-E, 17 ± 9 vs. 109 ± 22 BFU-E, 3 ± 1 vs. 9 ± 6 CFU-GEMM and 16 ± 10 vs. 66 ± 23 CFU-GM). The number of primitive bone marrow (BM) progenitor cells was also decreased (1.8 ± 1.4 vs. 15.4 ± 3.6 LTC-CFC/106 BMMCs). In addition, stromal cells secreted lower IL-7 levels (0.3 + 0.1 pg/mL vs. 0.8 + 0.1 pg/mL, in controls) and displayed by immunohistochemistry an altered phenotype. Upon light microscopy examination, the majority (75%) of these cells appeared as moderately large cells, frequently rounded, with abundant cytoplasm, whereas in control subjects about 90% of the stromal cells exhibited a different morphology characterized by irregular or spindle shape and branching cytoplasmic processes (fibroblast-like). Compared with normal subjects, thalassemia patients showed: reduction of naïve CD4+ T-cells (2 ± 0.5% vs 50 ± 10%), reduction of thymic naïve CD4+ T-cells (1 ± 0.2% vs 40 ± 12%,) and a significant increase of CD4+ cells activation markers (CD95, HLA-DR and CCR5). IL-7 receptor (CD127) expression was also significantly decreased on CD4+ T-cells and on naïve CD4+ T-cells (CD4+/CD45RA+CD62L+/CD127+). NK cells were among the first lymphocytes to repopulate the peripheral blood, and up to 70% of these cells were CD56 brigh whereas CD16+ NK cells were decreased. Conclusions. Twenty days post transplant, an impaired growth and differentiation capacity of stem/progenitor cells were observed in thalassemia patients, in parallel with an altered homeostasis of T-cells and a reduction of T-cell naïve compartment. We hypothesize that the damage of T cell compartment may be at least partially due to an altered production of new T cells starting from the haematopoietic stem/progenitor cells. CD56+ NK cells develop more rapidly than other lymphocytes, but CD16+ NK cells (with cytotoxic potential) require more prolonged exposure to maturation factors (IL-2) in the bone marrow. An IL7/IL7R pathway dysregulation has been also observed, possibly involving bone marrow stromal cells. In vitro studies are ongoing about the use of cytokines (IL-2, IL-7, IL-2 plus IL-7) supporting T cell development.

Early T Cell Recovery of Thymus-Derived Naive T Cells and NK Cells in Pediatrics Patients after T-Cell Depleted HLA-Haploidentical Stem Cell Transplantation for Thalassemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3816-3816 ◽  
Author(s):  
Antonella Isgro’ ◽  
Pietro Sodani ◽  
Marco Marziali ◽  
Buket Erer ◽  
Cecilia Alfieri ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Stem Cell ◽  
T Cell ◽  
Nk Cells ◽  
Cd8 T Cells ◽  
Stromal Cells ◽  
Cd4 T Cells ◽  
Th Cells ◽  
Post Transplant

Abstract Delayed immune recovery post transplant remains a significant obstacle and results in increased risk of infections. T cells are regenerated via 2 pathway, thymus-derived and peripheral expansion, processes for which IL-7 is critical. To analyse the mechanisms involved in immunological reconstitution, we studied six thalassemia patients after 20 and 60 days post T-cell-depleted HLA-haploidentical stem cell transplantation. The mean age ranged from 14 to 5 years. As controls, 6 healthy donors matched by sex and age with the patients were included. We analysed T cell subsets by flow cytometry. Stromal cells, obtained from long term culture of bone marrow mononuclear cells were analysed by immunohystochemistry and the stromal IL-7 production was analysed by ELISA. Day + 20 post transplant, the patients had significantly lower CD4+ T cells in comparison to the controls (1.9 ± 1.4% vs. 47.5 ± 6% respectively), and this reduced number was mainly observed in CD45RA+CD62L+ (naive phenotype) subset (1.3 ± 2% in patients vs. 52 ± 12% in controls). A significant decrease of peripheral CD45RA+CD31+ Th cells (thymic naive Th cells) (on average 0.5 ± 0.3% in patients vs. 37 ± 10% in controls) was observed, whereas CD8+ T cells numbers did not statistically differ between patients and controls (24.2 ± 33.7% vs. 20 ± 7%). NK cells were among the first lymphocytes to repopulate the peripheral blood, and up to 70% of these cells were CD56 bright whereas CD56dim CD16+ NK cells were reduced. Day + 60 post transplant an increase in the percentages of CD4+ T cells, naïve CD4+ cells and in thymic naïve Th cells were observed (3 ± 1.2%, 2.9 ± 2.1%, 2.7 ± 1%, respectively). CD8+ T cells were also increased (in mean 35 ± 27.5%). Compared with normal subjects, thalassemia patients showed a significant increase of CD4+ cell activation markers (CD95, HLA-DR and CCR5) and this was observed after 60 days post transplant, in parallel with the increase of the CD56dim CD16+ NK cells especially in the patients with full engraftment. Stromal cells secreted lower IL-7 levels (0.3 + 0.1 pg/mL vs. 0.8 + 0.1 pg/mL, in controls) and displayed by immunohistochemistry an altered phenotype (“macrophage-like” morphology). A significant decrease in total lymphocyte counts and depletion of CD4+ T cells expressing predominantly the CD45RA+CD62L+ phenotype were observed after 60 days post transplant. Also the CD4+CD45RA+CD31+ T cell subset was initially reduced but an increase has been observed at day + 60 post transplant, suggesting a thymus involvement in these patients. An IL7/IL7R pathway dysregulation has been also observed, possibly involving bone marrow stromal cells. NK cells were among the earliest lymphocytes to repopulate the peripheral blood, but. CD56dim CD16+ NK cells were increased after 60 days post transplant, especially in the patients with full engraftment, suggesting a role of donor NK cells on bone marrow engraftment. We hypothesize that the recovery of T cell compartment may be due to a deregulated production of new T cells starting from haematopoietic stem cells under the influence of stromal cytokines production.

Graft-Versus-Host Tolerance in Dogs Following T-Cell Depleted Bone Marrow Transplantation with Absorbed ATG or CD6-Antibody.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2338-2338
Author(s):  
Julia Zorn ◽  
Hans Jochem Kolb
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Stem Cell ◽  
Bone Marrow Transplantation ◽  
T Cell ◽  
Nk Cells ◽  
Marrow Transplantation ◽  
Graft Versus Host ◽  
Host Tolerance ◽  
Rabbit Complement

Abstract Graft-versus-host disease (GvHD) is the major obstacle of allogeneic stem cell transplantation. Depletion of T-cells from the graft reduces the risk of GvHD, but results in a higher risk of leukemia relapse. Adoptive immunotherapy with donor lymphocyte transfusion (DLT) has been shown to control leukemia in patients after T-cell depleted allogeneic stem cell transplantation. However, GvHD may occur, if DLT is given too early after transplantation. In canine models of DLA-identical and DLA-haploidentical bone marrow transplantation, we compared different methods of T-cell depletion (TCD) and investigated the potential of DLT at different times after transplantation to induce GvHD. T-cell depletion was performed either with absorbed anti-thymocyte globuline (aATG) or with a combination of CD6-antibody and baby rabbit complement. ATG was absorbed with erythrocytes, liver, kidney and spleen for eliminating antibodies against stem cells. CD6-antibody (M-T606) and rabbit complement depleted T-cells effectively without affecting hematopoietic progenitor cells. Unlike aATG, monoclonal CD6-antibody spares natural killer (NK) cells and some CD8-positive cells. Treatment of bone marrow with aATG prevented GvHD in 9 dogs following DLA-identical transplantation. DLT on days 1 and 2 or 21 and 22 induced fatal GvHD in two dogs each. However, it did not induce GvHD when given on days 61 and 62 and later. In DLA-haploidentical bone marrow recipients, non-manipulated marrow produced fatal GvHD in all dogs (n=7), whereas marrow treated with aATG (vol:vol 1:100 and 1:200) produced fatal GvHD in 5 out of 16 dogs only. CD6-depletion prevented GvHD in 3 of 3 DLA-haploidentically transplanted dogs. DLT produced fatal GvHD in one dog each, when given on day 3, 7 or 14 after CD6-depleted haploidentical bone marrow transplantation. However, it produced fatal GvHD in only 2 of 4 dogs transfused on day 20 post grafting. Thus, DLT could be given earlier in DLA-haploidentical animals transplanted with CD6-depleted marrow than in DLA-identical animals transplanted with aATG treated marrow without producing GvHD. These findings support the hypothesis that graft-versus-host tolerance can be induced earlier with grafts not depleted of NK cells. NK cells in the graft may inactivate host dendritic cells necessary for the induction of GvHD. In grafts depleted with aATG, NK cells are depleted as well, because aATG still retains broad specificity despite extensive absorptions. This leaves host DCs unaffected. Transfused donor T-cells encountering this environment will thus be activated which results in severe GvHD. In contrast, monoclonal CD6-antibody spares NK cells, so that donor lymphocytes cannot be activated by host DCs at the time of DLT and thus won’t trigger GvHD. CD6-depletion is the preferred method if adoptive immunotherapy with DLT is planned.

Expression of CD10 and CD7 Defines Distinct In Vivo Lymphoid Reconstituting Capacity within Human Cord Blood CD34+CD38-Cells.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3184-3184
Author(s):  
Shuro Yoshida ◽  
Fumihiko Ishikawa ◽  
Leonard D. Shultz ◽  
Noriyuki Saito ◽  
Mitsuhiro Fukata ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
B Cells ◽  
Cord Blood ◽  
Nk Cells ◽  
Progenitor Cells ◽  
Human Cord Blood ◽  
Cd34 Cells

Abstract Human cord blood (CB) CD34+ cells are known to contain both long-term hematopoietic stem cells (LT-HSCs) and lineage-restricted progenitor cells. In the past, in vitro studies suggested that CD10, CD7 or CD127 (IL7Ra) could be candidate surface markers that could enrich lymphoid-restricted progenitor cells in human CB CD34+ cells (Galy A, 1995, Immunity; Hao QL, 2001, Blood; Haddad R, 2004, Blood). However, in vivo repopulating capacity of these lymphoid progenitors has not been identified due to the lack of optimal xenogeneic transplantation system supporting development of human T cells in mice. We aim to identify progenitor activity of human CB CD34+ cells expressing CD10/CD7 by using newborn NOD-scid/IL2rgKO transplant assay that can fully support the development of human B, T, and NK cells in vivo (Ishikawa F, 2005, Blood). Although LT-HSCs exist exclusively in Lin-CD34+CD38- cells, not in Lin-CD34+CD38+ cells, CD10 and CD7 expressing cells are present in Lin-CD34+CD38- cells as well as in Lin-CD34+CD38+ cells (CD10+CD7+ cells, CD10+CD7- cells, CD10-CD7+ cells, CD10-CD7- cells accounted for 4.7+/−2.7%, 10.5+/−1.9%, 7.6+/−4.4%, and 77.1+/−5.2% in Lin-CD34+CD38- CB cells, respectively). We transplanted 500–6000 purified cells from each fraction into newborn NOD-scid/IL2rgKO mice, and analyzed the differentiative capacity. CD34+CD38-CD10-CD7- cells engrafted long-term (4–6 months) in recipient mice efficiently (%hCD45+ cells in PB: 30–70%, n=5), and gave rise to all types of human lymphoid and myeloid progeny that included granulocytes, platelets, erythroid cells, B cells, T cells, and NK cells. Successful secondary reconstitution by human CD34+ cells recovered from primary recipient bone marrow suggested that self-renewing HSCs are highly enriched in CD34+CD38–CD10–CD7- cells. CD10–CD7+ cells were present more frequently in CD34+CD38+ cells rather than in CD34+CD38- cells. Transplantation of more than 5000 CD34+CD38+CD10–CD7+ cells, however, resulted in less than 0.5% human cell engraftment in the recipients. Within CD34+CD38–CD10+ cells, the expression of CD7 clearly distinguished the distinct progenitor capacity. At 8 weeks post-transplantation, more than 70% of total human CD45+ cells were T cells in the CD10+CD7+ recipients, whereas less than 30% of engrafted human CD45+ cells were T cells in the CD10+CD7– recipients. In the CD10+CD7- recipients, instead, more CD19+ B cells and HLA–DR+CD33+ cells were present in the peripheral blood, the bone marrow and the spleen. Both CD34+CD38–CD10+CD7+ and CD34+CD38–CD10+CD7- cells highly repopulate recipient thymus, suggesting that these progenitors are possible thymic immigrants. Taken together, human stem and progenitor activity can be distinguished by the expressions of CD7 and CD10 within Lin-CD34+CD38- human CB cells. Xenotransplant model using NOD-scid/IL2rgKO newborns enable us to clarify the heterogeneity of Lin-CD34+CD38- cells in CB by analyzing the in vivo lymphoid reconstitution capacity.

Tigit, CD226 and PD-L1/PD-1 Are Highly Expressed By Marrow-Infiltrating T Cells in Patients with Multiple Myeloma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2102-2102 ◽  
Author(s):  
Mahesh Yadav ◽  
Cherie Green ◽  
Connie Ma ◽  
Alberto Robert ◽  
Andrew Glibicky ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Flow Cytometry ◽  
T Cells ◽  
T Cell ◽  
Nk Cells ◽  
Cd8 T Cells ◽  
Cd4 T Cells ◽  
Plasma Cells ◽  
Color Flow

Abstract Introduction:TIGIT (T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif [ITIM] domain) is an inhibitory immunoreceptor expressed by T and natural killer (NK) cells that is an important regulator of anti-tumor and anti-viral immunity. TIGIT shares its high-affinity ligand PVR (CD155) with the activating receptor CD226 (DNAM-1). We have recently shown that TIGIT blockade, together with PD-L1/PD-1 blockade, provides robust efficacy in syngeneic tumor and chronic viral infection models. Importantly, CD226 blockade abrogates the benefit of TIGIT blockade, suggesting additional benefit of TIGIT blockade through elaboration of CD226-mediated anti-tumor immunity, analogous to CTLA-4/CD28 regulation of T-cell immunity. Whether TIGIT and CD226 are expressed in patients with multiple myeloma (MM) and how TIGIT expression relates to PD-L1/PD-1 expression is unknown. Here we evaluate expression of TIGIT, CD226, PD-1 and PD-L1 in patients with MM to inform novel immunotherapy combinations. Methods:We performed multi-color flow cytometry (n = 25 patients), and multiplex qRT-PCR (n = 7) on bone marrow specimens from patients with MM to assess expression of TIGIT, CD226, PD-1, and PD-L1 on tumor and immune cells. Cells were stained with fluorescently conjugated monoclonal antibodies to label T cells (CD3, CD4, CD8), NK cells (CD56, CD3), plasma cells (CD38, CD45, CD319, CD56), inhibitory/activating receptors (PD-1, TIGIT, PD-L1, CD226), and an amine-reactive viability dye (7-AAD). Stained and fixed cells were analyzed by flow cytometry using BD FACSCanto™ and BD LSRFortessa™. Results:TIGIT, CD226 and PD-L1/PD-1 were detectable by flow cytometry in all patients with MM who were tested, with some overlapping and distinct expression patterns. TIGIT was commonly expressed by marrow-infiltrating CD8+ T cells (median, 65% of cells), CD4+ T cells (median, 12%) and NK cells. In contrast, CD226 was more commonly expressed by marrow-infiltrating CD4+ T cells (median, 74%) compared with CD8+ T cells (median, 38%). PD-1 was expressed by marrow-infiltrating CD8+ T cells (median 38%) and CD4+ T cells (median, 16%). TIGIT was co-expressed with PD-1 on CD8+ T cells (67%-97% TIGIT+ among PD-1+), although many PD-1-negative CD8+ T cells also expressed TIGIT (39%-78% of PD-1-negative). PD-L1 was also expressed by CD8+ (median, 23%) and CD4+ (median, 8%) T cells in addition to MM plasma cells (median, 95%), albeit with significantly lower intensity on T cells compared with plasma cells. The expression of TIGIT and PD-L1 mRNA was highly correlated (R2 = 0.80). Analysis of PVR expression will also be presented. Conclusions: TIGIT, CD226, PD-1, and PD-L1 were commonly expressed in MM bone marrow, but with different patterns. Among CD8+ T cells, the frequency of TIGIT+ T cells was almost twice that of PD-1+ T cells, whereas the majority of CD4+ T cells expressed CD226. TIGIT blockade may complement anti-PD-L1/PD-1 immunotherapy by activating distinct T-cell/NK-cell subsets with synergistic clinical benefit. These results provide new insight into the immune microenvironment of MM and rationale for targeting both the PD-L1/PD-1 interaction and TIGIT in MM. Disclosures Yadav: Genentech, Inc.: Employment. Green:Genentech, Inc.: Employment. Ma:Genentech, Inc.: Employment. Robert:Genentech, Inc.: Employment. Glibicky:Makro Technologies Inc.: Employment; Genentech, Inc.: Consultancy. Nakamura:Genentech, Inc.: Employment. Sumiyoshi:Genentech, Inc.: Employment. Meng:Genentech, Inc.: Employment, Equity Ownership. Chu:Genentech Inc.: Employment. Wu:Genentech: Employment. Byon:Genentech, Inc.: Employment. Woodard:Genentech, Inc.: Employment. Adamkewicz:Genentech, Inc.: Employment. Grogan:Genentech, Inc.: Employment. Venstrom:Roche-Genentech: Employment.

scholarly journals Mesenchymal Stromal Cells from Osteoarthritic Synovium Are a Distinct Population Compared to Their Bone-Marrow Counterparts regarding Surface Marker Distribution and Immunomodulation of Allogeneic CD4+ T-Cell Cultures

2016 ◽  
Vol 2016 ◽  
pp. 1-17 ◽  
Author(s):  
Sebastien Hagmann ◽  
Claudia Rimmele ◽  
Florin Bucur ◽  
Thomas Dreher ◽  
Felix Zeifang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Cd4 T Cells ◽  
Surface Marker ◽  
Cd4 T Cell ◽  
T Cell Proliferation

Introduction. The participation of an inflammatory joint milieu has been described in osteoarthritis (OA) pathogenesis. Mesenchymal stromal cells (MSCs) play an important role in modulating inflammatory processes. Based on previous studies in an allogeneic T-cell coculture model, we aimed at further determining the role of synovial MSCs in OA pathogenesis.Methods. Bone-marrow (BM) and synovial membrane (SM) MSCs from hip joints of late stage OA patients and CD4+ T-cells from healthy donors were analysed regarding surface marker expression before and after coculture. Proliferation upon CD3/CD28 stimulation and cytokine analyses were compared between MSCs.Results. SM-MSCs differed from BM-MSCs in several surface markers and their osteogenic differentiation potential. Cocultures of both MSCs with CD4+ T-cells resulted in recruitment of CD45RA+ FoxP3+ regulatory T-cells. Upon stimulation, only SM-MSCs suppressed CD4+ T-cell proliferation, while both SM-MSCs and BM-MSCs modified cytokine profiles through suppressing IL-2 and TNF-αas well as increasing IL-6 secretion.Conclusions. Synovial MSCs from OA joints are a unique fraction that can be distinguished from their bone-marrow derived counterparts. Their unique ability to suppress CD3/CD28 induced CD4+ T-cell proliferation makes them a potential target for future therapeutic approaches.

Allogeneic Rejection of High Grade Lymphoma: Evidence for Immune Escape in a Haploidentical Murine Model.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3171-3171
Author(s):  
Madhusudhanan Sukumar ◽  
Andrea Wilke ◽  
Josef Mautner ◽  
Hans-Jochem Kolb ◽  
Georg Bornkamm ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Stem Cell ◽  
T Cell ◽  
Cell Expansion ◽  
Immune Escape ◽  
High Grade ◽  
Lymphoma Cells ◽  
T Cell Expansion

Abstract Allogeneic stem cell transplantation for high grade lymphoma typically suffers from high transplant related mortality and minimal success in achieving long term complete remission. The immunological aspects behind rejection of high grade lymphoma are poorly understood, partly due to the lack of animal models. Using a transgenic mouse lymphoma model, where the proto-oncogene c-myc is driven by parts of the immunoglobulin lambda locus representing a t(8;22) translocation as found in Burkitt’s lymphoma, we developed a haploidentical transplantation model. c-myc-lambda transgenic C57/BL6 mice were crossbred with DBA mice, giving rise to a B6D2F1 generation which develops high grade lymphoma spontaneously within the first 6 months post birth. Primary F1-lymphoma cell lines displayed low MHC class I and class II expression compared to wild type B-cells. When transferred into immune-competent, healthy C57/BL6 parental mice, F1-lymphoma cells were rejected even at high doses of 50 Mio. cells, whereas the syngeneic transfer of 10,000 cells into B6D2F1 mice resulted in 100% mortality due to lymphoma growth. Immunosuppression of C57/BL6 mice by lethal total body irradiation and transplantation of T-cell depleted bone marrow allowed F1-lymphoma to grow when animals were challenged at day +1 after bone marrow transplantation with 1 Mio. cells. Addback of 2.5 or 10 Mio. parental T-cells together with F1-lymphoma on day +1 completely prevented lymphoma growth, and resulted in long term survival for more than 60 days. When T-cell addback was delayed until day +3 or +6 after lymphoma challenge, animals died due to lymphoma progression 7–8 days later. By using “green” T-cells from GFP transgenic C57/BL6 mice we could show that spleens 7 days after T-cell addback contained only 0.5% (15% of total CD3+ cells) GFP positive T-cells, whereas up to 15% (55%–75% of total CD3+ cells) of total splenocytes were GFP positive in long term survivors that rejected lymphoma. Similar results were obtained when T-cells were labelled with CFDA. This indicates that T-cell expansion is associated with lymphoma rejection; animals that receive T-cells after lymphoma has been established do not show any T-cell expansion, even when lymphoma cells display a haplo-mismatch and mature T-cells are co-localized within the spleen. T-Cell expansion is suppressed when lymphoma cells are present in splenic tissue, indicating efficient immune escape. Similar results were observed when bone marrow and T-cells from C57BL/6 donors were transplanted into irradiated B6D2F1 mice and 1 Mio. F1-lymphoma cells were injected on day +1 post transplantation. Despite the presence of GvHD when low number of T-cells (0.5–2.0 Mio.) were used lymphoma growth was measurable and animals eventually died due to disease progression. These results point to the crucial role of pretransplant lymphoma burden for the success of allogeneic stem cell transplantation in high grade lymphoma.

Chemotactic and chemokinetic activities of stem cell factor on murine hematopoietic progenitor cells

Blood ◽  
1996 ◽  
Vol 87 (10) ◽  
pp. 4100-4108 ◽  
Author(s):  
N Okumura ◽  
K Tsuji ◽  
Y Ebihara ◽  
I Tanaka ◽  
N Sawai ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Progenitor Cells ◽  
Stromal Cells ◽  
Stem Cell Factor ◽  
Hematopoietic Progenitor Cells ◽  
Hematopoietic Progenitor ◽  
Murine Bone Marrow ◽  
Checkerboard Assay

We investigated the effects of stem cell factor (SCF) on the migration of murine bone marrow hematopoietic progenitor cells (HPC) in vitro using a modification of the checkerboard assay. Chemotactic and chemokinetic activities of SCF on HPC were evaluated by the numbers of HPC migrated on positive and negative gradients of SCF, respectively. On both positive and negative gradients of SCF, HPC began to migrate after 4 hours incubation, and their numbers then increased time- dependently. These results indicated that SCF functions as a chemotactic and chemokinetic agent for HPC. Analysis of types of colonies derived from the migrated HPC showed that SCF had chemotactic and chemokinetic effects on all types of HPC. When migrating activities of other cytokines were examined, interleukin (IL)-3 and IL-11 also affected the migration of HPC, but the degrees of each effect were lower than that of SCF. The results of the present study demonstrated that SCF is one of the most potent chemotactic and chemokinetic factors for HPC and suggest that SCF may play an important role in the flow of HPC into bone marrow where stromal cells constitutively produce SCF.

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