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Microglia, a Product of Bone Marrow Stem Cells, Tie up Loose Ends of Ruptured Blood Vessels

Jun 13, 2016 1:00:50 PM / by Steffen Porwollik

Bone Marrow_AdobeStock_96184508-978099-edited.jpegScientists discover and visualize the astonishing capability of microglia, macrophages circulating in the brain, to repair broken blood vessels. This finding may open up new avenues for treatment of hemorrhagic strokes and brain microbleeds associated with dementia and cognitive decline.

Every four minutes, a person dies from a stroke in the US. A staggering 15 million people worldwide suffer from an occurrence of this disease every year. Strokes are thus incredibly common and extremely serious. The majority of these strokes is caused by a disruption of the blood flow to the brain, and therapy approaches using pluripotent stem cells show much promise. However, about 13% of strokes are hemorrhagic in nature, where brain blood vessels rupture and blood flows freely into the brain tissue.

In addition to these “macro-breaks”, small blood vessels in the brain rupture all the time, as people age. Usually, these microbleeds remain symptomless, but repeated occurrence is strongly associated with dementia and a general decline in cognitive abilities. Given the importance of blood vessel integrity, particularly in the brain, it is perhaps surprising that our knowledge on the mechanisms of cerebral vascular repair is still fairly rudimentary. A team of Chinese scientists set about to change that and recently published its astonishing observations. [1]

The researchers wanted to find out if and how the body can repair blood vessel ruptures in the brain. They turned to genetically modified zebrafish, which allowed fluorescent visualization of both brain vasculature and immune cells. Then they shot laser beams into the animals’ brains, introducing clean blood vessel breaks. Once the damage was done, they watched what would happen next.

About 30 minutes after the laser treatment, microglia, the bone-marrow derived brain-specific macrophages, were recruited to the sites of vessel rupture. The scientists looked on, probably open-mouthed, as one microgliocyte positioned itself between the ruptured ends of the blood vessel, extended its “arms” – filopodia or lamellopodia of up to 50 µm in length – on both sites, “glued” itself to the broken ends of the vascular cell and then used traction to pull the ends back together. The blood vessel was effectively repaired in about 3 hours. Once the repair job was done, the microgliocyte innocently floated away.

Using clever genetic modifications and imaging, the scientists went on to further characterize this wondrous process. They determined that external ATP was the signal that attracted microglia to the rupture sites. Repair was inhibited by blebbistatin, a myosin II inhibitor, which prevented traction, and latrunculin B, a depolymerization agent that prevented microfilament assembly by the microglia. Transcriptional analysis identified up-regulation of multiple genes, including Pl3K, which enables movement of the microglia, and Rac, which is needed to form the “arms” and adhesions. When both these genes were inhibited, the microglia were not able to do their repair job.

Microglia, such as those observed and visualized in this study, can be differentiated in vitro from non-adhesive bone marrow-derived stem cells. [2] HemaCare offers unprocessed bone marrow and bone marrow-derived stem cell populations for your research – do not hesitate to contact us at (877) 397-3087 to explore how our reasonably-priced cell products can further your research.

How will the new knowledge of microglia-dependent blood vessel repair be useful for therapies? Numerous potential avenues exist, including therapeutics that modify the number of microglia, those that work on Pl3K or Rac, or those that increase functionality of the microglia ATP receptors. Thanks to the Chinese scientists, it may not take a stroke of genius anymore to identify improved treatment options against one of the most common killers of human life.

References:

[1] Liu C, Wu C, Yang Q, Gao J, Li L, Yang D, et al. Macrophages mediate the repair of brain vascular rupture through direct physical adhesion and mechanical traction. Immunity. 2016 May 17; 44:1–15.

[2] Hinze A, Stolzing A. Microglia differentiation using a culture system for the expansion of mice non-adherent bone marrow stem cells. J Inflamm. 2012; 9:12.

Topics: Bone Marrow, Macrophages, Stem Cells, Basic Research

Steffen Porwollik

Written by Steffen Porwollik

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