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Updated: Aug 6, 2026
In Vivo Osteo-organoid Approach for Harvesting Therapeutic Hematopoietic Stem/Progenitor Cells
Published on: February 16, 2024
SOCS up-regulation mobilizes autologous stem cells through CXCR4 blockade
Oscar M Pello1, María del Carmen Moreno-Ortiz, José Miguel Rodríguez-Frade
1Centro Nacional de Biotecnología/CSIC, Darwin 3, Campus de Cantoblanco, E-28049, Madrid, Spain.
Abstract:
The chemokine CXCL12 influences self-renewal and differentiation of hematopoietic stem cell precursors in bone marrow by directing them toward specific stromalcell components. CXCL12 up-regulates members of the SOCS family through JAK/STAT activation, a mechanism that attenuates chemokine responses. SOCS expression may thus modulate retention of hematopoietic precursors (Sca-1(+) c-Kit(+)Lin(-) cells) in bone marrow. We show that in bovine growth hormone transgenic mice and in growth hormone-treated mice, SOCS up-regulation correlated with a large number of Sca-1(+) c-Kit(+)Lin(-) cells in blood. Retroviral transduction of SOCSs blocked in vitro migration of Sca-1(+)c-Kit(+)Lin(-) cells, as well as their capacity to reconstitute lethally irradiated mice. Furthermore, in lethally irradiated mice reconstituted with bone marrow infected by a tetracycline-regulated, SOCS-expressing lentiviral vector, doxycycline treatment promoted rapid, extensive precursor mobilization to the periphery. The results indicate that by blocking CXCR4-mediated functions, SOCSs modulate hematopoietic precursor cell retention in bone marrow, and suggest the therapeutic interest of SOCS manipulation in several pathologic situations.
Insights
Suppressor of Cytokine Signaling (SOCS) proteins regulate hematopoietic stem cell precursors in bone marrow. Manipulating SOCS expression can mobilize these cells, suggesting therapeutic potential.
Area of Science:
- Hematology
- Immunology
- Molecular Biology
Background:
- Chemokine CXCL12 directs hematopoietic stem cell precursors in bone marrow.
- CXCL12 signaling involves JAK/STAT activation and SOCS family upregulation.
- SOCS expression impacts hematopoietic precursor retention in bone marrow.
Purpose of the Study:
- To investigate the role of SOCS in hematopoietic precursor cell mobilization.
- To explore the therapeutic potential of modulating SOCS expression.
Main Methods:
- Utilized bovine growth hormone transgenic and growth hormone-treated mice models.
- Employed retroviral transduction and lentiviral vectors for SOCS manipulation.
- Assessed Sca-1(+) c-Kit(+)Lin(-) cell counts in blood and bone marrow.
- Evaluated in vitro cell migration and in vivo reconstitution capacity.
Main Results:
- SOCS upregulation correlated with increased Sca-1(+) c-Kit(+)Lin(-) cells in blood.
- Retroviral SOCS transduction inhibited cell migration and reconstitution potential.
- Doxycycline-induced SOCS expression promoted rapid precursor mobilization to the periphery.
Conclusions:
- SOCS proteins modulate hematopoietic precursor retention in bone marrow by affecting CXCR4-mediated functions.
- Targeting SOCS offers potential therapeutic strategies for various pathological conditions.
