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Citations to this article

Targeting VLA4 integrin and CXCR2 mobilizes serially repopulating hematopoietic stem cells
Darja Karpova, … , Daniel C. Link, John F. DiPersio
Darja Karpova, … , Daniel C. Link, John F. DiPersio
Published May 14, 2019
Citation Information: J Clin Invest. 2019;129(7):2745-2759. https://doi.org/10.1172/JCI124738.
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Research Article Article has an altmetric score of 5

Targeting VLA4 integrin and CXCR2 mobilizes serially repopulating hematopoietic stem cells

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Abstract

Mobilized peripheral blood has become the primary source of hematopoietic stem and progenitor cells (HSPCs) for stem cell transplantation, with a 5-day course of granulocyte colony-stimulating factor (G-CSF) as the most common regimen used for HSPC mobilization. The CXCR4 inhibitor plerixafor is a more rapid mobilizer, yet not potent enough when used as a single agent, thus emphasizing the need for faster acting agents with more predictable mobilization responses and fewer side effects. We sought to improve hematopoietic stem cell transplantation by developing a new mobilization strategy in mice through combined targeting of the chemokine receptor CXCR2 and the very late antigen 4 (VLA4) integrin. Rapid and synergistic mobilization of HSPCs along with an enhanced recruitment of true HSCs was achieved when a CXCR2 agonist was coadministered in conjunction with a VLA4 inhibitor. Mechanistic studies revealed involvement of CXCR2 expressed on BM stroma in addition to stimulation of the receptor on granulocytes in the regulation of HSPC localization and egress. Given the rapid kinetics and potency of HSPC mobilization achieved by the VLA4 inhibitor and CXCR2 agonist combination in mice compared with currently approved HSPC mobilization methods, the combination represents an exciting potential strategy for clinical development in the future.

Authors

Darja Karpova, Michael P. Rettig, Julie Ritchey, Daniel Cancilla, Stephanie Christ, Leah Gehrs, Ezhilarasi Chendamarai, Moses O. Evbuomwan, Matthew Holt, Jingzhu Zhang, Grazia Abou-Ezzi, Hamza Celik, Eliza Wiercinska, Wei Yang, Feng Gao, Linda G. Eissenberg, Richard F. Heier, Stacy D. Arnett, Marvin J. Meyers, Michael J. Prinsen, David W. Griggs, Andreas Trumpp, Peter G. Ruminski, Dwight M. Morrow, Halvard B. Bonig, Daniel C. Link, John F. DiPersio

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 Total
Citations: 1 8 5 1 9 5 3 32
Citation information
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Citations to this article (32)

Title and authors Publication Year
SERCA-mediated endoplasmic reticulum stress facilitates hematopoietic stem cell mobilization
Li L, Xu D, Huang X
Stem Cell Research & Therapy 2025
Small molecule-mediated CBP/p300 histone acetyltransferase inhibition mobilizes leukocytes from the bone marrow via the endocrine stress response
Jaschke NP, Breining D, Hofmann M, Pählig S, Baschant U, Oertel R, Traikov S, Grinenko T, Saettini F, Biondi A, Stylianou M, Bringmann H, Zhang C, Yoshida TM, Weidner H, Poller WC, Swirski FK, Göbel A, Hofbauer LC, Rauner M, Scheiermann C, Wang A, Rachner TD
Immunity 2024
Extramedullary hematopoiesis in cancer.
Barisas DAG, Choi K
Experimental & molecular medicine 2024
Targeting CXCR4, VLA-4, and CXCR2 for hematopoietic stem cell mobilization
Cancilla D, Rettig MP, Karpova D, Thakellapalli H, Singh M, Meyers MJ, Ruminski PG, Christ S, Chendamarai E, Gao F, Gehrs L, Ritchey JK, Prinsen M, DiPersio JF
Blood Advances 2024
A simplified G-CSF–free procedure allows for in vivo HSC gene therapy of sickle cell disease in a mouse model
Li C, Anderson AK, Ruminski P, Rettig M, Karpova D, Kiem HP, DiPersio JF, Lieber A
Blood Advances 2024
Development of VLA4 and CXCR4 Antagonists for the Mobilization of Hematopoietic Stem and Progenitor Cells
Ruminski PG, Rettig MP, DiPersio JF
Biomolecules 2024
Hematopoietic stem cell collection for sickle cell disease gene therapy
Leonard A, Weiss MJ
Current opinion in hematology 2024
Kmt2c restricts G-CSF-driven HSC mobilization and granulocyte production in a methyltransferase-independent manner
Wang HC, Chen R, Yang W, Li Y, Muthukumar R, Patel RM, Casey EB, Denby E, Magee JA
Cell reports 2024
Assessment of non-myelotoxic agents as a preparatory regimen for hematopoietic stem cell gene therapy.
Şeker ME, Erol ÖD, Pervin B, Wagemaker G, van Til NP, Aerts-Kaya F
Human cell 2024
Purinergic Signaling and Its Role in Mobilization of Bone Marrow Stem Cells.
Suszynska M, Adamiak M, Thapa A, Cymer M, Ratajczak J, Kucia M, Ratajczak MZ
Methods in molecular biology (Clifton, N.J.) 2023
Tumor-derived interleukin-1α and leukemia inhibitory factor promote extramedullary hematopoiesis.
Barisas DAG, Kabir AU, Wu J, Krchma K, Kim M, Subramanian M, Zinselmeyer BH, Stewart CL, Choi K
PLoS Biology 2023
Innovations in hematopoietic stem-cell mobilization: a review of the novel CXCR4 inhibitor motixafortide
Crees ZD, Rettig MP, DiPersio JF
Therapeutic Advances in Hematology 2023
Gata2 noncoding genetic variation as a determinant of hematopoietic stem/progenitor cell mobilization efficiency
Soukup AA, Bresnick EH
Blood Advances 2023
CXCR2 chemokine receptor – a master regulator in cancer and physiology
Lazennec G, Rajarathnam K, Richmond A
Trends in Molecular Medicine 2023
IL-1β expression in bone marrow dendritic cells is induced by TLR2 agonists and regulates HSC function
Li S, Yao JC, Oetjen KA, Krambs JR, Xia J, Zhang J, Schmidt AP, Helton NM, Fulton RS, Heath SE, Turnbull IR, Mbalaviele G, Ley TJ, Walter MJ, Link DC
Blood 2022
Hematopoietic Stem Cell Mobilization: Current Collection Approaches, Stem Cell Heterogeneity, and a Proposed New Method for Stem Cell Transplant Conditioning
JB Menendez-Gonzalez, J Hoggatt
Stem Cell Reviews and Reports 2021
Hematopoietic stem cell mobilization strategies to support high-dose chemotherapy: A focus on relapsed/refractory germ cell tumors
E Porfyriou, S Letsa, C Kosmas
World journal of clinical oncology 2021
TNF-α-induced alterations in stromal progenitors enhance leukemic stem cell growth via CXCR2 signaling
P Agarwal, H Li, K Choi, K Hueneman, J He, RS Welner, DT Starczynowski, R Bhatia
Cell Reports 2021
Comparison of the efficacy of hematopoietic stem cell mobilization regimens: a systematic review and network meta-analysis of preclinical studies
C Luo, L Wang, G Wu, X Huang, Y Zhang, Y Ma, M Xie, Y Sun, Y Huang, Z Huang, Q Song, H Li, Y Hou, , S Xu, J Chen
Stem Cell Research & Therapy 2021
In vitro and in vivo effects of AVA4746, a novel competitive antagonist of the ligand binding of VLA‑4, in B‑cell acute lymphoblastic leukemia
Y Ruan, H Kim, H Ogana, E Gang, S Li, HC Liu, D Bhojwani, A Wayne, M Yang, YM Kim
Experimental and therapeutic medicine 2021
The Nlrp3 inflammasome – the evolving story of its positive and negative effects on hematopoiesis
MZ Ratajczak, M Kucia
Current Opinion in Hematology 2021
Meloxicam with Filgrastim may Reduce Oxidative Stress in Hematopoietic Progenitor Cells during Mobilization of Autologous Peripheral Blood Stem Cells in Patients with Multiple Myeloma
AM Patterson, S Zhang, L Liu, H Li, P Singh, Y Liu, SS Farag, LM Pelus
Stem Cell Reviews and Reports 2021
Single-dose MGTA-145/plerixafor leads to efficient mobilization and in vivo transduction of HSCs with thalassemia correction in mice
C Li, KA Goncalves, T Raskó, A Pande, S Gil, Z Liu, Z Izsvák, T Papayannopoulou, JC Davis, HP Kiem, A Lieber
Blood Advances 2021
Extracellular Adenosine Triphosphate (eATP) and Its Metabolite, Extracellular Adenosine (eAdo), as Opposing “Yin–Yang” Regulators of Nlrp3 Inflammasome in the Trafficking of Hematopoietic Stem/Progenitor Cells
MZ Ratajczak, M Kucia
Frontiers in immunology 2021
G-CSF shifts erythropoiesis from bone marrow into spleen in the setting of systemic inflammation
W Jing, X Guo, F Qin, Y Li, G Wang, Y Bi, X Jin, L Han, X Dong, Y Zhao
2020
A Review of Advances in Hematopoietic Stem Cell Mobilization and the Potential Role of Notch2 Blockade
M Albakri, H Tashkandi, L Zhou
Cell Transplantation 2020
Uncovering the multifaceted roles played by neutrophils in allogeneic hematopoietic stem cell transplantation
C Tecchio, MA Cassatella
Cellular and Molecular Immunology 2020
Innate immunity orchestrates the mobilization and homing of hematopoietic stem/progenitor cells by engaging purinergic signaling—an update
MZ Ratajczak, M Adamiak, K Bujko, A Thapa, V Pensato, M Kucia, J Ratajczak, H Ulrich
Purinergic Signalling 2020
Salvage treatment with plerixafor in poor mobilizing allogeneic stem cell donors: results of a prospective phase II-trial
K Hölig, H Schmidt, G Hütter, M Kramer, R Teipel, K Heidrich, K Zimmer, F Heidenreich, M Blechschmidt, T Torosian, R Ordemann, F Kroschinsky, E Rücker-Braun, L Gopsca, EM Wagner-Drouet, U Oelschlaegel, AH Schmidt, M Bornhäuser, G Ehninger, J Schetelig
Bone Marrow Transplantation 2020
Bone marrow dendritic cells regulate hematopoietic stem/progenitor cell trafficking
Jingzhu Zhang, Teerawit Supakorndej, Joseph Krambs, Mahil Rao, Grazia Abou-Ezzi, Rachel Ye, Sidan Li, Kathryn Trinkaus, daniel c link
Journal of Clinical Investigation 2019
Mobilized peripheral blood: an updated perspective
D Karpova, MP Rettig, JF DiPersio
F1000Research 2019
An Overview of Novel Unconventional Mechanisms of Hematopoietic Development and Regulators of Hematopoiesis – a Roadmap for Future Investigations
K Bujko, M Cymer, M Adamiak, MZ Ratajczak
Stem Cell Reviews and Reports 2019

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