Apolipoprotein A-I Stimulates Cell Proliferation in Bone Marrow Cell Culture

Usynin, I. F.; Dudarev, A. N.; Gorodetskaya, A Yu; Miroshnichenko, Svetlana; Tkachenko, T. A.; Tkachenko, V I

doi:10.1007/s10517-018-3978-0

Cited by 5 publications

(5 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition to its role in cholesterol trafficking, Apo-A, a multifunctional protein, participates in inflammatory and immune responses [27]. It also stimulates the proliferation of monocytes, granulocytes and their progenitor cells and bone marrow MSCs [28] and supports MSC survival under stress conditions [29], which might be beneficial for hematopoiesis recovery [20]. Some studies revealed that exogenousfree Apo-A alters the characteristics of progenitor cell populations [30].…”

Section: Discussionmentioning

confidence: 99%

Apolipoprotein-A is a potential prognostic biomarker for severe aplastic anemia patients treated with ATG-based immunosuppressive therapy: a single-center retrospective study

Liu

Dong

et al. 2022

Lipids Health Dis

View full text Add to dashboard Cite

Background Anti-thymoglobulin (ATG)-based immunosuppressive treatment (IST) is the standard first-line management for patients with severe AA/very severe AA (SAA/VSAA) and is not suitable for allogeneic stem cell transplantation. The response predictor was not fully investigated. Objective The present study attempted to explore other characteristics, such as serum lipid changes, during ATG-based IST and analyzed their significance in predicting IST response and survival. Methods A total of 61 newly diagnosed SAA/VSAA patients who received ATG-based IST were enrolled from January 2011 to June 2019. The blood lipid levels, immunoglobulins, and peripheral T lymphocytes were retrospectively collected, and their correlations with IST response, estimated 8.5-year overall survival (OS) and event-free survival (EFS) were analyzed. Results The overall response (OR)/complete remission (CR) at 3, 6, and 9 months was 24.6%/6.6%, 52.5%/14.8%, and 65.6%/23.0%, respectively. Based on the 9-month response effect, patients were divided into IST-response (IST-R) and IST-nonresponse (IST-NR) groups. The subgroup baseline characteristics showed that the disease severity grade, absolute neutrophil granulocyte count (ANC), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and apolipoprotein-A (Apo-A) differed between the IST-R and IST-NR groups. Patients with lower Apo-A (< 1.205 g/L) level pretreatment had a better event-free survival (EFS), and a moderate negative correlation was established between the pretreatment Apo-A and 9-month response (P = 0.004). In addition, the T-cell subset and immunoglobulin analyses showed that the responsive patients had a low serum IgA level, which decreased further after therapy. Additionally, a moderate negative correlation was established between the 3-month IgA and 9-month response (P = 0.006). Conclusion Serum Apo-A is a prognostic biomarker for newly diagnosed < 60-year-old SAA/VSAA patients who received ATG-based IST (registered at chictr.org.cn as # ChiCTR2100052979).

show abstract

Section: Discussionmentioning

confidence: 99%

Apolipoprotein-A is a potential prognostic biomarker for severe aplastic anemia patients treated with ATG-based immunosuppressive therapy: a single-center retrospective study

Liu

Dong

et al. 2022

Lipids Health Dis

View full text Add to dashboard Cite

show abstract

“…As mentioned, ApoA-I itself is a biologically active protein that exhibits many properties in the body. The regulatory effect of ApoA-I on the proliferation and stem properties of mesenchymal stromal cells is shown in Miroshnichenko [ 58 ]. However, it should be emphasized that the activity of ApoA-I was manifested at concentrations [ 57 , 58 ] three orders of magnitude higher than the concentration of the recombinant forms of ryGM-CSF-ApoA-I and ryG-CSF-ApoA-I.…”

Section: Discussionmentioning

confidence: 99%

“…The regulatory effect of ApoA-I on the proliferation and stem properties of mesenchymal stromal cells is shown in Miroshnichenko [ 58 ]. However, it should be emphasized that the activity of ApoA-I was manifested at concentrations [ 57 , 58 ] three orders of magnitude higher than the concentration of the recombinant forms of ryGM-CSF-ApoA-I and ryG-CSF-ApoA-I. Other researchers obtained human interferon α2b (IFN) fused with ApoA-I, which showed more pronounced immunostimulatory activity, reduced hematotoxicity, and better pharmacokinetic properties compared to authentic IFN [ 59 ].…”

Section: Discussionmentioning

confidence: 99%

Construction of Recombinant Human GM-CSF and GM-CSF-ApoA-I Fusion Protein and Evaluation of Their Biological Activity

et al. 2021

View full text Add to dashboard Cite

In this study, two strains of the yeast P. pastoris were constructed, one of which produced authentic recombinant human granulocyte-macrophage colony-stimulating factor (ryGM-CSF), and the other was a chimera consisting of ryGM-CSF genetically fused with mature human apolipoprotein A-I (ApoA-I) (ryGM-CSF-ApoA-I). Both forms of the cytokine were secreted into the culture medium. The proteins’ yield during cultivation in flasks was 100 and 60 mg/L for ryGM-CSF and ryGM-CSF-ApoA-I, respectively. Both forms of recombinant GM-CSF stimulated the proliferation of human TF-1 erythroleukemia cells; however, the amount of chimera required was 10-fold that of authentic GM-CSF to induce a similar proliferative effect. RyGM-CSF exhibited a 2-fold proliferative effect on BFU-E (burst-forming units—erythroid) at a concentration 1.7 fold less than non-glycosylated E. coli-derived GM-CSF. The chimera together with authentic ryGM-CSF increased the number of both erythroid precursors and BMC granulocytes after 48 h of incubation of human bone marrow cells (BMCs). In addition, the chimeric form of ryGM-CSF was more effective at increasing the viability of the total amount of BMCs, decreasing apoptosis compared to the authentic form. ryGM-CSF-ApoA-I normalized the proliferation, maturation, and segmentation of neutrophils within the physiological norm, preserving the pool of blast cells under conditions of impaired granulopoiesis. The chimera form of GM-CSF exhibited the properties of a multilinear growth factor, modulating the activity of GM-CSF and, perhaps, it may be more suitable for the normalization of granulopoiesis.

show abstract

“…Highdensity lipoprotein (HDL) is a natural nanocarrier responsible for the transport of fat and other biomolecules (5). apoA-I is the major protein constituent of native HDL and interacts with scavenger receptors and the adenosine triphosphate (ATP)-binding cassette transporters ABCA1 and ABCG1, abundantly present on myeloid cells (6). On the basis of apoA-I, we developed innate immune cell-targeting nanocarriers, which we termed nanobiologics.…”

Section: Developing Nanobiologics With High Affinity For Myeloid Cellsmentioning

confidence: 99%

A modular approach toward producing nanotherapeutics targeting the innate immune system

et al. 2021

View full text Add to dashboard Cite

Immunotherapies controlling the adaptive immune system are firmly established, but regulating the innate immune system remains much less explored. The intrinsic interactions between nanoparticles and phagocytic myeloid cells make these materials especially suited for engaging the innate immune system. However, developing nanotherapeutics is an elaborate process. Here, we demonstrate a modular approach that facilitates efficiently incorporating a broad variety of drugs in a nanobiologic platform. Using a microfluidic formulation strategy, we produced apolipoprotein A1–based nanobiologics with favorable innate immune system–engaging properties as evaluated by in vivo screening. Subsequently, rapamycin and three small-molecule inhibitors were derivatized with lipophilic promoieties, ensuring their seamless incorporation and efficient retention in nanobiologics. A short regimen of intravenously administered rapamycin-loaded nanobiologics (mTORi-NBs) significantly prolonged allograft survival in a heart transplantation mouse model. Last, we studied mTORi-NB biodistribution in nonhuman primates by PET/MR imaging and evaluated its safety, paving the way for clinical translation.

show abstract

Apolipoprotein A-I Stimulates Cell Proliferation in Bone Marrow Cell Culture

Cited by 5 publications

References 11 publications

Apolipoprotein-A is a potential prognostic biomarker for severe aplastic anemia patients treated with ATG-based immunosuppressive therapy: a single-center retrospective study

Apolipoprotein-A is a potential prognostic biomarker for severe aplastic anemia patients treated with ATG-based immunosuppressive therapy: a single-center retrospective study

Construction of Recombinant Human GM-CSF and GM-CSF-ApoA-I Fusion Protein and Evaluation of Their Biological Activity

A modular approach toward producing nanotherapeutics targeting the innate immune system

Contact Info

Product

Resources

About