Delivery of human CD34+ cells and human peripheral non-selected blood mononuclear cells decreases neointima formation greater than culture-modified mononuclear cells in an immunodeficient rat carotid balloon injury model

2008 ◽  
Vol 9 (2) ◽  
pp. 118
Author(s):  
T Kiernan ◽  
B Yan ◽  
B Boilson ◽  
T Witt ◽  
R Simari
Keyword(s):  
Mononuclear Cells ◽  
Neointima Formation ◽  
Balloon Injury ◽  
Human Cd34 ◽  
Injury Model ◽  
Cd34 Cells ◽  
Blood Mononuclear Cells

scholarly journals Phenotype and function of human hematopoietic cells engrafting immune- deficient CB17-severe combined immunodeficiency mice and nonobese diabetic-severe combined immunodeficiency mice after transplantation of human cord blood mononuclear cells

Blood ◽  
1996 ◽  
Vol 88 (10) ◽  
pp. 3731-3740 ◽  
Author(s):  
F Pflumio ◽  
B Izac ◽  
A Katz ◽  
LD Shultz ◽  
W Vainchenker ◽  
...  
Keyword(s):  
Cord Blood ◽  
Progenitor Cells ◽  
Mononuclear Cells ◽  
Severe Combined Immunodeficiency ◽  
Human Cells ◽  
Scid Mice ◽  
Combined Immunodeficiency ◽  
Human Cd34 ◽  
Blood Mononuclear Cells ◽  
Cord Blood Mononuclear Cells

In an attempt to understand better the regulation of stem cell function in chimeric immunodeficient mice transplanted with human cells, and the filiation between progenitor cells identified in vitro and in vivo, we assessed the different compartments of hematopoietic progenitors found in the marrow of CB17-severe combined immunodeficiency (SCID) mice (34 mice, 9 experiments) after intravenous injection of 2 to 3 x 10(7) cord blood mononuclear cells. On average 6.3 +/-4 x 10(5) human cells were detected per four long bones 4 to 6 weeks after the transplant predominantly represented by granulomonocytic (CD11b+) and B lymphoid (CD19+) cells. Twenty five percent of these human cells expressed the CD34 antigen, of which 90% coexpressed the CD38 antigen and 50% the CD19 antigen. Functional assessment of progenitor cells (both clonogenic and long-term culture-initiating cells [LTC-IC]) was performed after human CD34+ cells and CD34+/CD38- cells have been sorted from chimeric CB17-SCID marrow 3 to 10 weeks after intravenous (IV) injection of human cells. The frequency of both colony-forming cells and LTC-IC was low (4% and 0.4%, respectively in the CD34+ fraction) when compared with the frequencies of cells with similar function in CD34+ cells from the starting cord blood mononuclear cells (26% +/- 7% and 7.2% +/- 5%, respectively). More surprisingly, the frequency of LTC-IC was also low in the human CD34+ CD38- fraction sorted from chimeric mice. This observation might be partly accounted for by the expansion of the CD34+ CD19+ B-cell precursor compartment. Despite their decreased frequency and absolute numbers, the differentiation capability of these LTC-IC, assessed by their clonogenic progeny output after 5 weeks in coculture with murine stromal cells was intact when compared with that of input LTC-IC. Furthermore the ratio between clonogenic progenitor cells and LTC-IC was similar in severe combined immunodeficiency (SCID) mice studied 4 weeks after transplant and in adult marrow or cord blood suspensions. Results generated in experiments where nonobese diabetic (NOD)-SCID mice were used as recipients indicate a higher level of engraftment but no change in the distribution of clonogenic cells or LTC-IC. These results suggest that the hierarchy of hematopoietic differentiation classically defined in human hematopoietic tissues can be reconstituted in immunodeficient SCID or NOD-SCID mice.

Abstract 14209: A New in vitro Methodology to Evaluate Blood Mononuclear Cells Regenerative Capacity in Diabetes Patients With Acute Myocardial Infarction

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Amankeldi A Salybekov ◽  
Katsuaki Sakai ◽  
Makoto Natsumeda ◽  
Kosit Vorateera ◽  
Yuji Ikari ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Cell Therapy ◽  
Mononuclear Cells ◽  
Roc Curve Analysis ◽  
Regenerative Capacity ◽  
Cd34 Cells ◽  
Blood Mononuclear Cells ◽  
M1 Type

Introduction & Hypothesis: Diabetes mellitus patients’(DMP) peripheral blood mononuclear cells (PBMNC) regenerative capacity level is impaired. An in vitro evaluation of PBMNC pre/post vasculogenic conditioning (VC) facilitates the assessment of immune cells regenerative potential (H1) and possible cell therapy for DMP with acute myocardial infarction (AMI) (H2). Materials & Methods: Eighteen DMP with the diagnosis of AMI enrolled. Blood drawn in heparin-coated syringes from AMI patients (between day 3 to 7) along with sixteen healthy control. Isolated PBMNC regenerative capability evaluated pre and post VC ( Fig 1 ) with EPCs colony formation assay/unit (EPC-CFA/U) and flow cytometry analysis. Results: An in vitro EPC-CFA revealed that DMP fresh PBMNC derived definitive EPC (DEPC) decreased compared to control. The differentiation rate of EPC, definitive vs. primitive in control groups composed equal (50%, PEPC vs. 50%, DEPC) while in DMP, PEPC prevails (70% vs. 30%). After VC, DEPC-CFU markedly increased while PEPC-CFU decreased, indicating EPC qualitatively and quantitatively improvement in DMP (Control, PBMNC vs. VC P>0.001; DMP, PBMNC vs. VC, P>0.01). DMP glycoalbumin and Hb1Ac inversely correlated with CD34+ cells (r= -0.48, P>0.03) while VC recovered CD34+ cells (r= 0.17, P<0.54). ROC curve analysis also confirmed that the CD34+ cell number is an independent risk classifier of cardiac vessel lesion (AUC=0.85, P>0.002). In contrast, VC preserved from the senescence by expansion and differentiation of CD34+ (AUC=0.54, P<0.7). Proinflammatory M1 type significantly increased in DMP compared to Control (P>0.03), while VC shifted the M1 type phenotype toward M2 type (P>0001). Conclusion: Our EPC-CFA enables us to precisely assess impaired EPC function, while VC enhanced differentiation from PEPC toward DEPC. Furthermore, these methodologies facilitate the evaluation of RACs capacities such as EPC, M1/M2, and Treg cells in DMP with AMI for cell therapy.

scholarly journals High potassium intake inhibits neointima formation in the rat carotid artery balloon injury model

2000 ◽  
Vol 13 (9) ◽  
pp. 1014-1020 ◽  
Author(s):  
G. Ma ◽  
D. B. Young ◽  
B. R. Clower ◽  
P. G. Anderson ◽  
H. Lin ◽  
...  
Keyword(s):  
Carotid Artery ◽  
Neointima Formation ◽  
Balloon Injury ◽  
High Potassium ◽  
Potassium Intake ◽  
Injury Model

Identification Of Specific Hematopoietic Populations Present In Peripheral Blood Mononuclear Cells That Increase Erythroid Output Directly Or Through Feeder/Stromal Cell-Like Properties

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3414-3414
Author(s):  
Esther Heideveld ◽  
Valentina Tirelli ◽  
Francesca Masiello ◽  
Fatemehsadat Esteghamat ◽  
Nurcan Yagci ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Fold Increase ◽  
Cell Contact ◽  
Peripheral Blood Mononuclear ◽  
Effector Cells ◽  
Cd34 Cells ◽  
Blood Mononuclear Cells

Abstract Hematopoietic development occurs in defined niches that ensure specific interactions and cross-talk with the surrounding stromal cells and different hematopoietic cells themselves. For instance, erythropoiesis occurs on the macrophage island within the bone marrow and the central macrophage is believed to regulate pro-erythroblast differentiation, the final stages of enucleation and reticulocyte maturation. We have observed that the expansion of erythroblasts from total peripheral blood mononuclear cells is increased compared to CD34+ Hematopoietic Stem/Progenitor Cells (HS(P)C) isolated from the same amount of blood [van den Akker, Haematologica, 2010]. This suggests i) the presence of CD34-cells that contribute to erythropoiesis and/or ii) that cell-cell contact or specific secreted growth factors by “helper” cells in these cultures can regulate hematopoiesis/erythropoiesis to increase erythroblast yield. Identifying the specific population(s) underlying the increased erythroid yield and understanding their way of action and regulatory mechanism during HSC differentiation and erythropoiesis is not only important to improve erythroblast culture conditions but may also provide clues to the function of hematopoietic effector cells in the various HS(P)C/erythroblast niches. Using specific lineage depletion (among which CD3 and CD14) we have identified and quantified various human erythroid and non-erythroid CD34+ and CD34- populations on the basis of CD36 co-expression in peripheral blood mononuclear cells (PBMC). Erythroid outgrowth from these CD34- populations and CD34+ populations and their contribution to the total erythroid yield from PBMC was assessed. Interestingly, total erythroid yield from the individual sorted populations did not reach the erythroid yield obtained from total PBMC. We hypothesized that support/feeder cells present in total PBMC are positively influencing in vitro erythropoiesis. In agreement with this, PBMC immuno-depletion of specific hematopoietic cell types identified CD14 cells (monocyte/macrophages) and to a lesser extend CD3 cells (lymphocytes) to be also partly responsible for the increased erythroblast yield. Compared to HS(P)C alone, co-culture of CD14 cells and HS(P)C isolated from PBMC resulted in a 5-10 times increase in CD71high/CD235med erythroblasts. Conditioned medium of CD14 cells as well as transwell experiments reconstituted the effect of the HS(P)C-CD14 co-cultures to 70%-80%, indicating that cell-cell contact plays a minor role. CD14 cells could elicit their effect at different stages during HSPC/HSC differentiation to erythroblasts. Co-culture of CD14 cells with pro-erythroblasts did not increase the cellular yield or proliferation rate. In contrast, two days of CD14 co-culture with CD34+ cells results in a 5 fold increase of total colony forming units without altering the colony lineage dynamics. In agreement with this a 5 fold increase in CD34+ cells was observed. These results indicate that CD14 cells elicit their effect on early hematopoietic progenitors but not on the erythroblast population. The results predict that depletion of CD14+ cells from PBMC should result in a decrease in the total number of CD34+cells. Indeed, we observed a 2 fold decrease of specifically HS(P)Cs and MEPs after two days of culture in PBMCs depleted for CD14 cells. Taken together our data i) identify previously unrecognized erythroid and non erythroid CD34- and CD34+ populations in peripheral blood that contribute to erythroid yield from total PBMC and ii) indicate modulation of HS(P)C outgrowth by specific hematopioietic effector cells present in peripheral blood that can also be found near specific hematopoietic niches in the bone marrow. The involvement of CD3 and CD14 immune cells suggests that HS(P)C and erythropoiesis may be modulated by immune-responses. Disclosures: No relevant conflicts of interest to declare.

Discovery of a Potent and Selective αvβ3 Integrin Antagonist with Strong Inhibitory Activity Against Neointima Formation in Rat Balloon Injury Model.

ChemInform ◽  
2004 ◽  
Vol 35 (39) ◽  
Author(s):  
Seiji Iwama ◽  
Tomoko Kitano ◽  
Fumiyo Fukuya ◽  
Yayoi Honda ◽  
Yuji Sato ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Αvβ3 Integrin ◽  
Neointima Formation ◽  
Balloon Injury ◽  
Injury Model

Platelet-derived microparticles bind to hematopoietic stem/progenitor cells and enhance their engraftment

Blood ◽  
2001 ◽  
Vol 98 (10) ◽  
pp. 3143-3149 ◽  
Author(s):  
Anna Janowska-Wieczorek ◽  
Marcin Majka ◽  
Jacek Kijowski ◽  
Monika Baj-Krzyworzeka ◽  
Ryan Reca ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Mononuclear Cells ◽  
Clinical Implications ◽  
Hematopoietic Stem ◽  
Human Cd34 ◽  
Hematopoietic Reconstitution ◽  
Cd34 Cells ◽  
Platelet Binding ◽  
Mobilized Peripheral Blood

Abstract Because human CD34+ and murine Sca-1+hematopoietic stem–progenitor cells (HSPCs) express platelet-binding sialomucin P-selectin (CD162) and integrin Mac-1 (CD11b–CD18) antigen, it was inferred that these cells might interact with platelets. As a result of this interaction, microparticles derived from platelets (PMPs) may transfer many platelet antigens (CD41, CD61, CD62, CXCR4, PAR-1) to the surfaces of HSPCs. To determine the biologic significance of the presence of PMPs on human CD34+ and murine Sca-1+ cells, their expressions on mobilized peripheral blood (mPB) and on nonmobilized PB- and bone marrow (BM)–derived CD34+ cells were compared. In addition, the effects of PMPs on the proliferation of CD34+ and Sca-1+ cells and on adhesion of HSPCs to endothelium and immobilized SDF-1 were studied. Finally, the hematopoietic reconstitution of lethally irradiated mice receiving transplanted BM mononuclear cells covered or not covered with PMPs was examined. It was found that PMPs are more numerous on mPB than on BM CD34+cells, do not affect the clonogenicity of human and murine HSPCs, and increase adhesion of these cells to endothelium and immobilized SDF-1. Moreover, murine BM cells covered with PMPs engrafted lethally irradiated mice significantly faster than those not covered, indicating that PMPs play an important role in the homing of HSPCs. This could explain why in a clinical setting human mPB HSPCs (densely covered with PMPs) engraft more rapidly than BM HSPCs (covered with fewer PMPs). These findings indicate a new role for PMPs in stem cell transplantation and may have clinical implications for the optimization of transplantations.

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