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Busulfan as a Myelosuppressive Agent for Generating Stable High-level Bone Marrow Chimerism in Mice
Published on: April 1, 2015
The human bone marrow harbors a CD45- CD11B+ cell progenitor permitting rapid microglia-like cell derivative
Andreas Bruzelius1,2, Isabel Hidalgo1,3, Antonio Boza-Serrano4,5
1Division of Neurosurgery, Department of Clinical Sciences Lund, Skåne University Hospital, Lund Stem Cell Center, Lund, Sweden.
Abstract:
Microglia, the immune sentinel of the central nervous system (CNS), are generated from yolk sac erythromyeloid progenitors that populate the developing CNS. Interestingly, a specific type of bone marrow-derived monocyte is able to express a yolk sac microglial signature and populate CNS in disease. Here we have examined human bone marrow (hBM) in an attempt to identify novel cell sources for generating microglia-like cells to use in cell-based therapies and in vitro modeling. We demonstrate that hBM stroma harbors a progenitor cell that we name stromal microglial progenitor (STR-MP). STR-MP single-cell gene analysis revealed the expression of the consensus genetic microglial signature and microglial-specific genes present in development and CNS pathologies. STR-MPs can be expanded and generate microglia-like cells in vitro, which we name stromal microglia (STR-M). STR-M cells show phagocytic ability, classically activate, and survive and phagocyte in human brain tissue. Thus, our results reveal that hBM harbors a source of microglia-like precursors that can be used in patient-centered fast derivative approaches.
Insights
Researchers discovered a new source of microglia-like cells in human bone marrow stroma. These stromal microglial progenitors (STR-MPs) can be used for cell therapies and in vitro modeling of central nervous system (CNS) conditions.
Area of Science:
- Neuroimmunology
- Stem Cell Biology
- Cellular Therapeutics
Background:
- Microglia are the primary immune cells of the central nervous system (CNS), originating from yolk sac progenitors.
- Bone marrow-derived monocytes can adopt microglial signatures and infiltrate the CNS during disease states.
- Identifying alternative sources for microglia is crucial for cell-based therapies and research models.
Purpose of the Study:
- To investigate human bone marrow (hBM) for novel progenitor cells capable of generating microglia-like cells.
- To characterize these potential precursors for therapeutic and modeling applications in CNS disorders.
Main Methods:
- Single-cell gene expression analysis of cells isolated from hBM stroma.
- In vitro expansion and differentiation of identified progenitor cells.
- Functional assays including phagocytosis and classical activation of generated cells.
- Assessment of cell survival and function within human brain tissue.
Main Results:
- A novel progenitor cell, termed stromal microglial progenitor (STR-MP), was identified in hBM stroma.
- STR-MPs express key microglial signature genes, mirroring developmental and pathological profiles.
- STR-MPs can be expanded in vitro to generate microglia-like cells (STR-M).
- STR-M cells exhibit phagocytic activity, classical activation, and functionality in human brain tissue.
Conclusions:
- Human bone marrow stroma contains a valuable source of microglia-like precursors (STR-MPs).
- These precursors can be readily expanded and differentiated into functional microglia-like cells (STR-M).
- STR-MPs offer a promising avenue for patient-centered, rapid cell-based therapeutic strategies and in vitro CNS modeling.
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