Large Animal Models for Stem and Progenitor Cell Analysis

Donahue, Robert E.; Kuramoto, Ken; Dunbar, Cynthia E.

doi:10.1002/0471142735.im22a01s69

Cited by 32 publications

(43 citation statements)

References 36 publications

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“…Thus, we have undertaken a study using the well-established rhesus macaque model of mobilization and leukapheresis. 15,[18][19][20][21][22][23] Our results document rapid and significant mobilization of all conventional T-cell populations after exposure to AMD3100 as well as enhanced mobilization of Tregs and effector memory T-cell populations. These results suggest that AMD3100-based mobilization may promote a GVHD-protective lymphocyte content and are therefore significant both for allo-HSCT as well as for strategies designed to mobilize both effector and regulatory lymphocyte populations for adoptive cellular therapies.…”

Section: Introductionmentioning

confidence: 74%

Significant mobilization of both conventional and regulatory T cells with AMD3100

Kean

Sen

Onabajo

et al. 2011

Blood

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In this study, we used the rhesus macaque model to determine the impact that AMD3100 has on lymphocyte mobilization, both alone and in combination with G-CSF. Our results indicate that, unlike G-CSF, AMD3100 substantially mobilizes both B and T lymphocytes into the peripheral blood. This led to significant increases in the peripheral blood content of both effector and regulatory T-cell populations, which translated into greater accumulation of these cells in the resulting leukapheresis products. Notably, CD4 ؉ / CD25 high /CD127 low /FoxP3 ؉ Tregs were efficiently mobilized with AMD3100-containing regimens, with as much as a 4.0-fold enrichment in the leukapheresis product compared with G-CSF alone. CD8 ؉ T cells were mobilized to a greater extent than CD4 ؉ T cells, with accumulation of 3.7 ؎ 0.4-fold more total CD8؉ T cells and 6.2 ؎ 0.4-fold more CD8 ؉ effector memory T cells in the leukapheresis product compared with G-CSF alone.Given that effector memory T-cell subpopulations may mediate less GVHD compared with other effector T-cell populations and that Tregs are protective against GVHD, our results indicate that AMD3100 may mobilize a GVHD-protective T-cell repertoire, which would be of benefit in allogeneic hematopoietic stem cell transplantation. (Blood. 2011;118(25): 6580-6590) IntroductionThe widespread use of cytokine-mediated mobilization has had a major impact on hematopoietic stem cell transplantation (HSCT). For auto-HSCT, peripheral blood-derived stem cell (PBSC) transplantation is associated with more rapid hematopoietic reconstitution and better outcomes compared with bone marrow transplantation. [1][2][3][4][5] For allo-HSCT, the choice is more complex. A metaanalysis showed that PBSC transplants in adults resulted in more rapid hematopoietic reconstitution, decreased relapse, and increased disease-free survival compared with bone marrow transplantation 6 but did not lead to an overall survival advantage compared with bone marrow, except in patients with late-stage disease. 6 This was probably because of the higher T-cell content of PBSC grafts (10-to 50-fold more than bone marrow-derived allografts), [7][8][9] leading to a significantly greater risk of GVHD. 6 In pediatrics, this increased risk of GVHD and transplant-related mortality shifted the risk/benefit balance, favoring bone marrow over PBSCs. 10 These dichotomous results between pediatric and adult patients suggest that a narrow therapeutic window exists for infused lymphocytes.With the FDA approval of AMD3100 (Plerixafor or Mozobil), 11 mobilization can now occur by multiple regimens, including G-CSF alone, AMD3100 alone, or G-CSF plus AMD3100. Therefore, the risks and benefits of each of these mobilization strategies must be understood and compared with those associated with bone marrow transplantation. AMD3100 is US Food and Drug Administration (FDA)-approved for auto-HSCT, and the combination of G-CSF and AMD3100 was shown to be superior to G-CSF for stem cell mobilization. 12-14 Furthermore, there was accelerated lymphocyte recov...

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Section: Introductionmentioning

confidence: 74%

Significant mobilization of both conventional and regulatory T cells with AMD3100

Kean

Sen

Onabajo

et al. 2011

Blood

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“…2 On the last day of irradiation autologous CD34 1 cells were reinfused after being transduced once (multiplicity of infection [MOI] 5 50) with a SIV/HIV chimeric lentiviral vector expressing EGFP. 3 …”

Section: Cd34mentioning

confidence: 99%

“…After digestion, the reaction mixture was purified using protein A-Sepharose affinity chromatography (Thermo Scientific), followed by dialysis in phosphate-buffered saline (PBS) using a dialysis membrane cassette with 20-kDa molecular weight cutoff at 4°C for 22 hours, and concentrated using a Centriprep YM-50 membrane (Amicon) to a concentration of 5.2 mg/mL. Protein purity was assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (Invitrogen) and size-exclusion high-performance liquid chromatography (HPLC; Gilson) equipped with a size-exclusion TSK gel G3000SWXL column ( Tc between HYNIC-F(ab9) 2 and free HYNIC when analyzed by size-exclusion HPLC. The reaction mixture was diluted 10 times with the same PBS and concentrated by Amicon 50K.…”

Section: Preparation Of F(ab9) 2 Anti-cd4 Antibodiesmentioning

confidence: 99%

“…2 This model has allowed us to evaluate immune recovery of rhesus macaques transplanted with immunoselected CD34 1 cells transduced with retroviral vectors. Most recently, we developed a chimeric lentiviral vector containing portions of the HIV and the simian immunodeficiency virus (SIV) which efficiently transduces rhesus CD34 1 cells and expresses enhanced green fluorescent protein (EGFP) as a marker to determine the contributions of the transduced CD34 1 cells to various elements of the hematopoietic lineage posttransplant.…”

Section: Introductionmentioning

confidence: 99%

“…For lymphoid recovery, peripheral blood (PB) lymphocytes (PBLs) have been used for analysis, but they represent <2% of cells in lymphoid tissues (LTs). Using a combination of single-photon emission computed tomography imaging and a radiotracer ( 99m Tc-labeled rhesus immunoglobulin G1 anti-CD4R1 (Fab9) 2 ), we sequentially imaged CD4…”

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Discordance in lymphoid tissue recovery following stem cell transplantation in rhesus macaques: an in vivo imaging study

Donahue

Srinivasula

Uchida

et al. 2015

Blood

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Myeloid‐Lymphoid Ontogeny in the Rhesus Monkey (Macaca mulatta)

Batchelder

Duru

Lee

et al. 2014

The Anatomical Record

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Establishment of a functional immune system has important implications for health and disease, yet questions remain regarding the mechanism, location, and timing of development of myeloid and lymphoid cell compartments. The goal of this study was to characterize the ontogeny of the myeloid-lymphoid system in rhesus monkeys to enhance current knowledge of the developmental sequence of B cell (CD20, CD79), T cell (CD3, CD4, CD8, FoxP3), dendritic cell (CD205), and macrophage (CD68) lineages in the fetus and infant. Immunohistochemical assessments addressed the temporal and spatial expression of select phenotypic markers in the developing liver, thymus, spleen, lymph nodes, gut-associated lymphoid tissue (GALT), and bone marrow with antibodies known to cross-react with rhesus cells. CD3 was the earliest lymphoid marker identified in the first trimester thymus and, to a lesser extent, in the spleen. T cell markers were also expressed mid-gestation on cells of the liver, spleen, thymus, and in Peyer’s patches of the small and large intestine, and where CCR5 expression was noted. A myeloid marker, CD68, was found on hepatic cells near blood islands in the late first trimester. B cell markers were observed mid-second trimester in the liver, spleen, thymus, lymph nodes, bone marrow spaces, and occasionally in GALT. By the late third trimester and postnatally, secondary follicles with germinal centers were present in the thymus, spleen, and lymph nodes. These results suggest that immune ontogeny in monkeys is similar in temporal and anatomical sequence when compared to humans, providing important insights for translational studies.

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Large Animal Models for Stem and Progenitor Cell Analysis

Cited by 32 publications

References 36 publications

Significant mobilization of both conventional and regulatory T cells with AMD3100

Significant mobilization of both conventional and regulatory T cells with AMD3100

Discordance in lymphoid tissue recovery following stem cell transplantation in rhesus macaques: an in vivo imaging study

Myeloid‐Lymphoid Ontogeny in the Rhesus Monkey (Macaca mulatta)

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