In vivo depletion of hematopoietic stem cells in the rat by an anti-CD45 (RT7) antibody

Dahlke, Marc H.; Lauth, Oliver S.; Jäger, Mark D.; Roeseler, Till; Timrott, Kai; Jackobs, Stefan; Neipp, Michael; Wonigeit, K.

doi:10.1182/blood.v99.10.3566

Cited by 23 publications

(20 citation statements)

References 27 publications

(25 reference statements)

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“…The difference in expression rates of CD49f (integrin ·6) and Á‰TCR was marginal and no difference was noted in the expression rates of CD90 (Thy-1), CD34 and CD29 (integrin ß1) between the two fractions. Substantial expression of CD45 is known to be observed in virtually all committed hematopoietic cells (25,26). When the cells were analyzed after double immunolabeling, positive cells in the expression of CD117 or CD200 were found solely in the CD45-positive populations (Fig.…”

Section: Expression Of Marker Proteins In the Cells Recovered In Mnc mentioning

confidence: 93%

Efficient differentiation into skin cells of bone marrow cells recovered in a pellet after density gradient fractionation

Medina

Kataoka²,

Miyazaki³

et al. 2006

Int J Mol Med

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Abstract. We had previously demonstrated the participation of whole bone marrow cells from adult mice in the reconstitution of skin, including the epidermis and hair follicles. To get an insight into cell populations that give rise to the epithelial components of the reconstituted skin, we fractionated bone marrow cells derived from green fluorescent proteintransgenic mice by density gradient. Unexpectedly, we found that a substantial amount of mononucleated cells (~30%) was recovered in the pellet fraction and that the cells in the pellet fraction preferentially differentiated into epithelial components of skin, rather than the cells in the mononuclear cell fraction. The pellet fraction contained more CD45-negative (thus uncommitted to the hematopoietic cell lineage) cells than the mononuclear cell fraction. These results indicate that density gradient fractionation results in significant loss of specific progenitor cells into the usually discarded pellet fraction.

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Section: Expression Of Marker Proteins In the Cells Recovered In Mnc mentioning

confidence: 93%

Efficient differentiation into skin cells of bone marrow cells recovered in a pellet after density gradient fractionation

Medina

Kataoka²,

Miyazaki³

et al. 2006

Int J Mol Med

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“…An alternative, potentially more specific and thus less toxic approach to conditioning is the use of monoclonal antibodies directed against stem cell antigens or more common leukocyte antigens. 173 Although it is likely that side effects associated with conditioning regimens will be reduced significantly in the near future, this issue will continue to be an important aspect of the risk-benefit evaluation for stem cell-based gene therapy.…”

Section: Risks Related To Conditioning Use Of Selective Drugs and Cmentioning

confidence: 99%

Side effects of retroviral gene transfer into hematopoietic stem cells

Baum

Düllmann

et al. 2003

Blood

384

241

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Recent conceptual and technical improvements have resulted in clinically meaningful levels of gene transfer into repopulating hematopoietic stem cells. At the same time, evidence is accumulating that gene therapy may induce several kinds of unexpected side effects, based on preclinical and clinical data. To assess the therapeutic potential of genetic interventions in hematopoietic cells, it will be important to derive a classification of side effects, to obtain insights into their underlying mechanisms, and to use rigorous statistical approaches in comparing data. We here review side effects related to target cell manipulation; vector production; transgene insertion and expression; selection procedures for transgenic cells; and immune surveillance. We also address some inherent differences between hematopoiesis in the most commonly used animal model, the laboratory mouse, and in humans. It is our intention to emphasize the need for a critical and hypothesis-driven analysis of "transgene toxicology," in order to improve safety, efficiency, and prognosis for the yet small but expanding group of patients that could benefit from gene therapy. (Blood. 2003;

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“…Results from a congenic stem-cell transplantation study in rats demonstrated that by using an isoform-specific anti-CD45 mAb treatment, a significant depletion of host stem cells could indeed be obtained. 25 However, further research is needed to address the efficiency of this approach.NK-cell function is coordinated by complex interactions between different inhibitory and activating receptors, 26,27 making it difficult to study the mechanism responsible for NK-cell tolerance. Preliminary data of Ly49A and Ly49D expression on host NK cells support the conclusion that the observed NK-cell nonresponsiveness was indeed the result of NK-cell tolerance.…”

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confidence: 99%

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confidence: 99%

Long-term mixed chimerism after immunologic conditioning and MHC-mismatched stem-cell transplantation is dependent on NK-cell tolerance

Westerhuis

Maas

Willemze

et al. 2005

Blood

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IntroductionAllogeneic stem-cell transplantation (SCT) is a potential treatment modality for different malignant and nonmalignant diseases. 1 However, the application of this approach is hampered by the high conditioning-related toxicity, graft-versus-host disease, graft rejection, and the limited availability of major histocompatibility (MHC)-matched siblings. 2 A reduction in morbidity and mortality would greatly facilitate a widespread application of hematopoietic SCT. To achieve successful acceptance of allogeneic stem cells in the absence of cytoreduction, the induction of donor-specific tolerance is mandatory. Because T cells play a key role in the rejection of allogeneic stem cells, most transplantation studies have focused on the induction of T-cell tolerance.Natural killer (NK) cells represent another barrier that prevents engraftment following transplantation over MHC barriers. Because of their ability to kill virus-infected or malignant host cells without prior sensitization, NK cells are part of the first line of defense against pathogens. Their activation is coordinated by different inhibitory and activating receptors. Classic and nonclassic MHC class I molecules function as ligands for these receptors and a perturbation of the class I expression, due to virus-infection or tumorigenesis, can result in NK-cell activation. 3-5 Differences in MHC class I expression on allogeneic hematopoietic cells can also result in NK-cell alloreactivity, making NK cells potential effector cells in the early rejection of hematopoietic stem cells. 6 However, data concerning NK-cell elimination of allogeneic stem cells have been inconclusive. Some studies demonstrate an important role for NK cells in the elimination of allogeneic cells, 7-9 whereas other studies indicate that allogeneic stem cells are relatively resistant toward NK-cell cytotoxicity. 10,11 In this study, we used an in vivo cytotoxicity assay based on the infusion of differentially carboxyfluorescein succinimidyl ester (CFSE)-labeled syngeneic and allogeneic donor splenocytes to analyze the elimination kinetics of MHC-mismatched hematopoietic cells in an anti-CD40 ligand (anti-CD40L)-based BALB/c into C57BL/6 SCT model in the complete absence of cytoreduction. We demonstrate the importance of NK cells in the elimination of MHC-mismatched hematopoietic cells after the induction of T-cell tolerance and further show that transplantation of a high dose of stem cells is required to induce NK-cell tolerance. Finally, we show that additional NK-cell depletion allows engraftment and the induction of long-term chimerism after transplantation of a reduced number of stem cells. Materials and methods MiceC57BL/6 (H-2 b ), BALB/c (H-2 d ), C3H/J (H-2 k ), and BALB/c nu/nu (H-2 d ) mice were purchased from Charles River Laboratories (Maastricht, The Netherlands), and C57BL/6 nu/nu (H-2 b ) mice were purchased from EDRIS A. Brunink (Valburg, The Netherlands). All mice were female, 8 to 12 weeks old at the start of each experiment, and maintained in the animal faciliti...

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In vivo depletion of hematopoietic stem cells in the rat by an anti-CD45 (RT7) antibody

Cited by 23 publications

References 27 publications

Efficient differentiation into skin cells of bone marrow cells recovered in a pellet after density gradient fractionation

Efficient differentiation into skin cells of bone marrow cells recovered in a pellet after density gradient fractionation

Side effects of retroviral gene transfer into hematopoietic stem cells

Long-term mixed chimerism after immunologic conditioning and MHC-mismatched stem-cell transplantation is dependent on NK-cell tolerance

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