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Study Confirms the Presence of Bone Marrow-derived Myeloid Progenitors in the Brain

Review of "Bone marrow-derived myeloid progenitors in the leptomeninges of adult mice" from STEM CELLS by Stuart P. Atkinson

A range of studies has shown that brain tissue damage can induce the transit of hematopoietic stem/progenitor cells from the bone marrow through the peripheral blood to engraft in the brain and differentiate into microglia‐like cells [1-4]. Furthermore, another study highlighted the induced transit of hematopoietic stem/progenitor cells to the central nervous system after cerebral ischemia to potentially limit damage [5].

A new study from researchers led by Stefanie Kuerten (Rheinische Friedrich‐Wilhelm Universität Bonn, Bonn, Germany) hoped to fully understand the extent and nature of hematopoietic stem/progenitor cells transit through the central nervous system under steady‐state conditions. Reporting in a recent STEM CELLS article [6], Koeniger et al. now confirm the presence of bone marrow-derived myeloid progenitors in the leptomeninges of the brain (literally "thin meninges," and comprise the arachnoid and pia mater) and now provide a platform for a better understanding of central nervous system surveillance and local immune cell production.

Briefly, the authors identified a range of myeloid progenitors present in the leptomeninges of adult C57BL/6 mice (including common myeloid, granulocyte/macrophage, and megakaryocyte/erythrocyte progenitors) that gave rise to all major myelo‐erythroid lineages in clonogenic culture assays. Leptomeningeal myeloid progenitors appeared at a frequency of 7 ± 4 per 105 isolated cells, equating to an estimated total number of 40 to 70 progenitors per mouse brain.

Their persistence after tissue perfusion and their inaccessibility to intravenous antibodies suggested a localization behind the blood vessel endothelium, while lineage tracing and bone marrow transplantation provided evidence for their derivation from hematopoietic stem/progenitor cells and continuous replacement by cell trafficking. Interestingly, the study also revealed that alterations to the immunologic state of the central nervous system correlated with the appearance of leptomeningeal myeloid progenitors; as examples, experimental autoimmune encephalomyelitis and ischemic stroke in model mice prompted a reduction in the number of myeloid progenitors resident in the leptomeninges.

The authors underscore the future research aims that will clarify their findings; these include determining the possible residence of myeloid progenitors within the brain parenchyma and elucidating the functional roles of the leptomeningeal myeloid progenitor population, which may include central nervous system surveillance and local immune cell production.

For more on the role of hematopoietic stem/progenitor cells in the central nervous system, stay tuned to the Stem Cells Portal!


References

  1. Capotondo A, Milazzo R, Garcia-Manteiga JM, et al., Intracerebroventricular delivery of hematopoietic progenitors results in rapid and robust engraftment of microglia-like cells. Science Advances 2017;3:e1701211.
  2. Capotondo A, Milazzo R, Politi LS, et al., Brain conditioning is instrumental for successful microglia reconstitution following hematopoietic stem cell transplantation. Proceedings of the National Academy of Sciences 2012;109:15018.
  3. Kierdorf K, Katzmarski N, Haas CA, et al., Bone Marrow Cell Recruitment to the Brain in the Absence of Irradiation or Parabiosis Bias. PLOS ONE 2013;8:e58544.
  4. Ajami B, Bennett JL, Krieger C, et al., Infiltrating monocytes trigger EAE progression, but do not contribute to the resident microglia pool. Nature Neuroscience 2011;14:1142-1149.
  5. Mocco J, Afzal A, Ansari S, et al., SDF1-A Facilitates Lin−/Sca1+ Cell Homing following Murine Experimental Cerebral Ischemia. PLOS ONE 2014;9:e85615.
  6. Koeniger T, Bell L, Mifka A, et al., Bone marrow-derived myeloid progenitors in the leptomeninges of adult mice. STEM CELLS 2021;39:227-239.