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Pericytes as adult stem cells

stem cells

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#1 timedilation

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Posted 12 January 2021 - 01:42 AM

Came across this interesting book chapter which argues that pericytes are adult pluripotent stem cells.  It doesn't seem to be a common idea, so I thought I would share it: https://sci-hub.se/1...-030-11093-2_13


Some relevant quotes:



The stem cells (ancestors) of the testicular Leydig cells are the pericytes and the smooth muscle cells of the microvasculature. Both cell types share the same lineage.  The pericytes are distributed during embryogenesis throughout the organism by the developing cardiovascular system that is the first functioning organ system during the embryonal development...The pericytes are pluripotent cells, such as the epiblast. They possess ectodermal, endodermal, and mesodermal lineage progeny which underlines their plasticity and heterogeneity.



The testis pericytes behave as authentic stem cells (Davidoff et al. 2004, 2009). After activation they start to proliferate, self-renew, and migrate out from the vascular niche to the perivascular space and the interstitium in form of transit-amplifying (intermediate) cells which transdifferentiate and generate multipotent stromal (mesenchymal) cells, resp., immature committed cells. The resulting cells, under the influence of the existing local factors, differentiate further as typical for an organ or cell culture mature cell phenotype (Leydig cells, smooth muscle cells, peritubular myoid cells, macrophages, fibroblasts, germ cells—DeFalco et al. 2015; Yoshida et al. 2007) characteristic for the organ or tissue in which they are situated. This illustrates the high plasticity of and how the pericytes adopt their phenotype when transplanted in another place or organ and provides evidence that the pericytes are true stem cells.



The pericytes are the ancestors of the multipotent adult stromal cells and the only authentic adult stem cell (ASC) phenotype of the vertebrate organism. Thus, the migrating transit-amplifying pericyte descendants represent the mul-tipotent mesodermal (until shortly mesenchymal stem) stromal cells.



It becomes evident that the pericytes represent the only true pluripotent adult stem cell in the mature vertebrate organism.



We propose that once the pericyte has migrated into the perivascular space it makes functional and phenotypic adjustments or adaptations that may include differentiation along multiple lineages and that this is the basis for their pluripotentiality...After their activation, proliferation, and migration, they become transit-amplifying cells that transdifferentiate to give different multipotent progenitors. With the continuation of the differentiation, the progenitor cells lose their multipotency and become oligopotent and unipotent.





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#2 timedilation

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Posted 12 January 2021 - 05:09 PM

Another good article on pericytes in brain injury: https://www.ncbi.nlm...les/PMC5350040/


Some highlights:


-Pericytes are pluripotent, can differentiate into SMC, fibroblast, endothelial cells, astrocytes, microglial cells, and even neurons in different induction.  "In mature adult brains, pericytes maintain low rate of turnover. Pathological insult can increase the proliferation rate of pericytes in pre-existing pools around brain vessels and recruit pericyte progenitor cells from bone marrow. Pericytes are not only self-renewable but also have the capacity to differentiate into other types of CNS cells."  They are reported to be involved in neurogenesis after brain injury.


-Pericytes help regulate BBB function by preventing leukocyte infiltration, assisting endothelial cells, regulating the basal lamina, and maintaining astrocytes.


-Pericytes can perform phagocytosis to clear debris.


-Regulate cerebral blood flow and induce angiogenesis.  Produce VEGF and have receptors for angiopoietin and PDGF-B.


-Can express BDNF and NGF.



And a bunch of other stuff too.  I wonder if we will eventually find that pericytes are a critical target for age-related decline and injury.  Increasing their proliferation or optimizing their function could potentially be a useful therapy in the future.



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