scholarly journals Engraftment, fate, and function of HoxB8-conditional neutrophil progenitors in the unconditioned murine host

2021 ◽  
Author(s):  
Joshua T. Cohen ◽  
Michael Danise ◽  
Kristina D. Hinman ◽  
Brittany M. Neumann ◽  
Renita Johnson ◽  
...  
Keyword(s):  
Cell Lines ◽  
Progenitor Cell ◽  
Dependent Manner ◽  
Myeloid Progenitor ◽  
Myeloid Progenitor Cell ◽  
Innovative Tool ◽  
And Function ◽  
Hematopoietic Niche ◽  
Β2 Integrins

The development and use of murine myeloid progenitor cell lines that are conditionally immortalized through expression of HoxB8 has provided a valuable tool for studies of neutrophil biology. Recent work has extended the utility of HoxB8-conditional progenitors to the in vivo setting via their transplantation into irradiated mice. Here, we describe the isolation of HoxB8-conditional progenitor cell lines that are unique in their ability to engraft in the naïve host in the absence of conditioning of the hematopoietic niche. Our results indicate that HoxB8-conditional progenitors engraft in a β1 integrin-dependent manner and transiently generate donor-derived mature neutrophils. Furthermore, we show that neutrophils derived in vivo from transplanted HoxB8-conditional progenitors are mobilized to the periphery and recruited to sites of inflammation in a manner that depends on the C-X-C chemokine receptor 2 and β2 integrins, the same mechanisms that have been described for recruitment of endogenous primary neutrophils. Together, our studies advance the understanding of HoxB8-conditional neutrophil progenitors and describe an innovative tool that, by virtue of its ability to engraft in the naïve host, will facilitate mechanistic in vivo experimentation on neutrophils.

IL-31 Receptor and IL-31 in the Positive Regulation of Myeloid Progenitor Cell Proliferation/Survival.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1347-1347
Author(s):  
Hal E. Broxmeyer ◽  
Nico Ghilardi ◽  
Giao Hangoc ◽  
Scott Cooper ◽  
Wen Tao ◽  
...  
Keyword(s):  
Colony Formation ◽  
Progenitor Cell ◽  
S Phase ◽  
Oncostatin M ◽  
Littermate Control ◽  
Gm Csf ◽  
Myeloid Progenitor ◽  
Myeloid Progenitor Cell

Abstract Interleukin (IL)-31 receptor (R), also called gp130-like monocyte-receptor (GLM-R; Ghilardi et al. J. Biol. Chem.277:16831, 2002) is related to gp130 (~25% homology), and G-CSF-R (~24%). Its signaling activates STAT3 and STAT5. IL-31 is a four helix bundle cytokine preferentially produced by T helper 2 cells. Nothing is known of the possible hematopoietic effects of IL-31R and IL-31. However, since: IL-31 signals through a receptor composed of IL-31RA and Oncostatin M R (Dillon et al. Nature Immunol. 5:752,2004), Oncostatin M is implicated in homeostasis of myeloid progenitor cells (Broxmeyer et al. Immunity.16:815, 2002), and STAT3 and 5 are implicated by a number of groups in cytokine regulation of hematopoiesis, we hypothesized that the IL-31/IL-31R axis would be involved in regulation of hematopoiesis. We first compared myeloid progenitor cell (MPC: CFU-GM, BFU-E, and CFU-GEMM) numbers and cycling status in marrow and spleen of IL-31R −/− vs. littermate control mice (+/+) using a combination of Epo, SCF and PWMSCM to stimulate in vitro the cells taken from these mice. IL-31R −/− mice had significantly decreased numbers of MPC per femur (~51%) and spleen (~36–45%) with significantly decreased MPC cycling status in marrow (% MPC in S-phase: 0–3% in IL-31R −/− vs. 41–53% in +/+ mice). MPC in spleen of IL-31 −/− and +/+ were both in a slow or non cycling state (0–3% in S-phase). In contrast to CFU-GM from +/+ mice, CFU-GM from IL-31R −/− mice demonstrated little or no synergistic response to combined stimulation in vitro with GM-CSF or IL-3 with either SCF or Flt3-ligand (FL). This translated to decreased absolute numbers per femur of GM-CSF+SCF-, GM-CSF+FL-, IL-3+SCF-, and IL-3+FL- responsive CFU-GM in IL-31R −/− mice. However, there were no significant differences between GM-CSF- or IL-3- responsive CFU-GM per femur between IL-31R −/− vs. +/+ mice suggesting effects on immature subsets of MPC. Recombinant IL-31 was assessed for effects in vitro. IL-31, at concentrations up to 100ng/ml, did not stimulate colony formation by marrow MPC, nor did it enhance or suppress colony formation stimulated by GM-CSF, Epo, Epo+SCF, or Epo+SCF+GM-CSF. However, IL-31 did enhance survival of MPC subjected to delayed growth factor addition in a manner similar to, but not as potent as, that of SDF-1/CXCL12. IL-31 manifested no chemotaxis activity for +/+ MPC, and IL-31R −/− and +/+ MPC were equally responsive to the chemotactic effects of SDF-1/CXCL12. These results suggest that the IL-31R in vivo acts to positively regulate numbers and cycling of immature subsets of MPC in the marrow, and that IL-31 has survival enhancing effects on MPC in vitro.

scholarly journals Grafts Derived from an α-Synuclein Triplication Patient Mediate Functional Recovery but Develop Disease-Associated Pathology in the 6-OHDA Model of Parkinson’s Disease

2020 ◽  
pp. 1-14
Author(s):  
Shelby Shrigley ◽  
Fredrik Nilsson ◽  
Bengt Mattsson ◽  
Alessandro Fiorenzano ◽  
Janitha Mudannayake ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Lines ◽  
Functional Recovery ◽  
Embryonic Stem ◽  
Hesc Line ◽  
Alternative Source ◽  
And Function

Background: Human induced pluripotent stem cells (hiPSCs) have been proposed as an alternative source for cell replacement therapy for Parkinson’s disease (PD) and they provide the option of using the patient’s own cells. A few studies have investigated transplantation of patient-derived dopaminergic (DA) neurons in preclinical models; however, little is known about the long-term integrity and function of grafts derived from patients with PD. Objective: To assess the viability and function of DA neuron grafts derived from a patient hiPSC line with an α-synuclein gene triplication (AST18), using a clinical grade human embryonic stem cell (hESC) line (RC17) as a reference control. Methods: Cells were differentiated into ventral mesencephalic (VM)-patterned DA progenitors using an established GMP protocol. The progenitors were then either terminally differentiated to mature DA neurons in vitro or transplanted into 6-hydroxydopamine (6-OHDA) lesioned rats and their survival, maturation, function, and propensity to develop α-synuclein related pathology, were assessed in vivo. Results: Both cell lines generated functional neurons with DA properties in vitro. AST18-derived VM progenitor cells survived transplantation and matured into neuron-rich grafts similar to the RC17 cells. After 24 weeks, both cell lines produced DA-rich grafts that mediated full functional recovery; however, pathological changes were only observed in grafts derived from the α-synuclein triplication patient line. Conclusion: This data shows proof-of-principle for survival and functional recovery with familial PD patient-derived cells in the 6-OHDA model of PD. However, signs of slowly developing pathology warrants further investigation before use of autologous grafts in patients.

Strontium can increase some osteoblasts without increasing hematopoietic stem cells

Blood ◽  
2008 ◽  
Vol 111 (3) ◽  
pp. 1173-1181 ◽  
Author(s):  
Stefania Lymperi ◽  
Nicole Horwood ◽  
Stephen Marley ◽  
Myrtle Y. Gordon ◽  
Andrew P. Cope ◽  
...  
Keyword(s):  
Trabecular Thickness ◽  
Hematopoietic Stem ◽  
Hematopoietic Recovery ◽  
Parallel Change ◽  
Hsc Niche ◽  
And Function ◽  
Hematopoietic Niche ◽  
In Vitro Treatment

Abstract Osteoblasts are a key component in the regulation of the hematopoietic stem cell (HSC) niche. Manipulating osteoblast numbers results in a parallel change in HSC numbers. We tested the activity of strontium (Sr), a bone anabolic agent that enhances osteoblast function and inhibits osteoclast activity, on hematopoiesis. In vitro treatment of primary murine osteoblasts with Sr increased their ability to form bone nodules, and in vivo it increased osteoblast number, bone volume, and trabecular thickness and decreased trabecular pattern factor. However, the administration of Sr had no influence on primitive HSCs, although the number of hematopoietic progenitors was higher than in control cells. When Sr-treated mice were used as donors for HSC transplantation, no difference in the engraftment ability was observed, whereas hematopoietic recovery was delayed when they were used as recipients. Despite the changes in osteoblast numbers, no increment in the number of N-cadherin+ osteoblasts and N-cadherin transcripts could be detected in Sr-treated mice. Therefore, increasing the overall number and function of osteoblasts without increasing N-cadherin+ cells is not sufficient to enhance HSC quantity and function. Our study further supports the notion that N-cadherin+ osteoblasts are fundamental in the hematopoietic niche.

scholarly journals Silver Nanoparticles Induce Mitochondrial Protein Oxidation in Lung Cells Impacting Cell Cycle and Proliferation

Antioxidants ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 552 ◽  
Author(s):  
Reetta J. Holmila ◽  
Stephen A. Vance ◽  
S. Bruce King ◽  
Allen W. Tsang ◽  
Ravi Singh ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Silver Nanoparticles ◽  
Ionizing Radiation ◽  
Cell Lines ◽  
Protein Oxidation ◽  
Mitochondrial Protein ◽  
Antibacterial Properties ◽  
Dependent Manner ◽  
Mitochondrial Redox State ◽  
And Function

Silver nanoparticles (AgNPs) are widely used nanomaterials in both commercial and clinical biomedical applications, due to their antibacterial properties. AgNPs are also being explored for the treatment of cancer in particular in combination with ionizing radiation. In this work, we studied the effects of AgNPs and ionizing radiation on mitochondrial redox state and function in a panel of lung cell lines (A549, BEAS-2B, Calu-1 and NCI-H358). The exposure to AgNPs caused cell cycle arrest and decreased cell proliferation in A549, BEAS-2B and Calu-1, but not in NCI-H358. The mitochondrial reactive oxygen species (ROS) and protein oxidation increased in a time- and dose-dependent manner in the more sensitive cell lines with the AgNP exposure, but not in NCI-H358. While ionizing radiation also induced changes in the mitochondrial redox profiles, in general, these were not synergistic with the effects of AgNPs with the exception of NCI-H358 and only at a higher dose of radiation.

scholarly journals Alantolactone inhibits cell autophagy and promotes apoptosis via AP2M1 in acute lymphoblastic leukemia

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Ce Shi ◽  
Wenjia Lan ◽  
Zhenkun Wang ◽  
Dongguang Yang ◽  
Jia Wei ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Tumor Growth ◽  
Cell Lines ◽  
Lymphoblastic Leukemia ◽  
Dependent Manner ◽  
Nude Mouse Model ◽  
Hematopoietic Malignancy ◽  
Induced Apoptosis ◽  
Anti Tumor Activity

Abstract Background Acute lymphoblastic leukemia (ALL) is an aggressive hematopoietic malignancy that is most commonly observed in children. Alantolactone (ALT) has been reported to exhibit anti-tumor activity in different types of cancer. The aim of the present study was to investigate the anti-tumor activity and molecular mechanism of ALT in ALL. Methods ALL cell lines were treated with 1, 5 and 10 μM ALT, and cell viability was assessed using an MTT assay and RNA sequencing. Flow cytometry, JC-1 staining and immunofluorescence staining assays were used to measure cell apoptosis and autophagy. Additionally, western blot analysis was used to detect expression of apoptosis and autophagy related proteins. Finally, the effects of ALT on tumor growth were assessed in a BV173 xenograft nude mouse model. Results ALT inhibited the proliferation of ALL cells in a dose-dependent manner. Additionally, it was demonstrated that ALT inhibited cell proliferation, colony formation, autophagy, induced apoptosis and reduced tumor growth in vivo through upregulating the expression of adaptor related protein complex 2 subunit mu 1 (AP2M1). Moreover, the autophagy activator rapamycin, attenuated the pro-apoptotic effects of ALT on BV173 and NALM6 cell lines. Overexpression of AP2M1 decreased the expression of Beclin1 and the LC3-II/LC3-1 ratio, and increased p62 expression. Knockdown of Beclin1 increased the levels of bax, cleaved caspase 3 and cytochrome C, and decreased bcl-2 expression. Conclusions The present study demonstrated that ALT exerts anti-tumor activity through inducing apoptosis and inhibiting autophagy by upregulating AP2M1 in ALL, highlighting a potential therapeutic strategy for treatment of ALL.

scholarly journals Recombinant granulocyte colony-stimulating factor administration to healthy volunteers: induction of immunophenotypically and functionally altered neutrophils via an effect on myeloid progenitor cells

Blood ◽  
1993 ◽  
Vol 82 (11) ◽  
pp. 3265-3272 ◽  
Author(s):  
JM Kerst ◽  
M de Haas ◽  
CE van der Schoot ◽  
IC Slaper-Cortenbach ◽  
M Kleijer ◽  
...  
Keyword(s):  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Myeloid Progenitor ◽  
Leukocyte Alkaline Phosphatase ◽  
Subcutaneous Dose ◽  
Myeloid Progenitor Cells ◽  
Membrane Bound ◽  
And Function ◽  
Stimulating Factor

Abstract We performed a detailed kinetic study on the in vivo effect of a single subcutaneous dose of granulocyte colony-stimulating factor (G-CSF; 300 micrograms) in four healthy individuals on the expression and function of neutrophil Fc gamma receptors (Fc gamma R). G-CSF did not induce Fc gamma RI (CD64) on circulating neutrophils. However, neutrophils newly formed in response to G-CSF were Fc gamma RI positive and were able to perform antibody-dependent cellular cytotoxicity in an Fc gamma RI- dependent way. Fc gamma RII (CD32) expression was not changed significantly. Fc gamma RIII (CD16, phosphatidylinositol-linked) expression, slightly increased immediately (30 minutes) postinjection, was found to be strongly decreased on the newly formed population. For comparison, we studied the expression of the PI-linked proteins leukocyte alkaline phosphatase (LAP) and CD14. Intracellular levels of LAP mirrored the biphasic expression pattern as membrane-bound Fc gamma RIII. In contrast, CD14 expression on neutrophils was initially constant, followed by high levels on the newly formed neutrophils. Soluble CD14 levels were found to be elevated transiently, whereas peak levels of soluble Fc gamma III were observed as late as 6 days postinjection. In conclusion, we have shown that G-CSF results in an immunophenotypically and functionally altered neutrophil population for an important part as a result of its effect on myeloid precursor cells.

scholarly journals Normal myeloid progenitor cell subset-associated gene signatures for acute myeloid leukaemia subtyping with prognostic impact

PLoS ONE ◽  
2020 ◽  
Vol 15 (4) ◽  
pp. e0229593 ◽  
Author(s):  
Anna A. Schönherz ◽  
Julie Støve Bødker ◽  
Alexander Schmitz ◽  
Rasmus Froberg Brøndum ◽  
Lasse Hjort Jakobsen ◽  
...  
Keyword(s):  
Acute Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Progenitor Cell ◽  
Cell Subset ◽  
Prognostic Impact ◽  
Gene Signatures ◽  
Myeloid Progenitor ◽  
Myeloid Progenitor Cell ◽  
Acute Myeloid
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