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Under the Microscope: Pericytes

  

María Dolores Salinas, MSc
University of Murcia
Murcia, Spain

Rut Valdor, PhD
University of Murcia
Murcia, Spain

Declarations of interest: none.

Staining for alpha-smooth muscle actin (α-SMA, in red) and NESTIN (in green). Scale bar: 50 μm.

What?
Pericytes are cells that surround the walls of small blood vessels and maintain the architecture of the endothelia in capillaries, venules and arterioles. Pericytes are a heterogeneous population in terms of origin, morphology and localization, presenting a different behaviour depending on the surrounding microenvironment. This cell type is not only involved in vessel contraction as smooth muscle cells would do in big vessels, but it also contributes in the angiogenesis process of new vessel formation. Importantly, pericytes are multipotent cells that present stem cell like-properties such as self-renewal, secretion of extracellular vesicles (EVs) with regenerative factors, release of cytokines and immunomodulation function. Pericytes act as defense cells with immune properties, phagocytic ability and, specifically in the central nervous system, pericytes are key components forming the neurovascular unit (NVU) to maintain and establish brain homeostasis through the integrity protection of the blood-brain barrier (BBB) (1–3).
Why?
Pericytes have the ability to filter substances, including drugs, thereby regulating what can pass through them to the tissue parenchyma. Moreover, due to their mesenchymal stromal cell (MSC) properties, pericytes have the capability to influence and modify the behaviour of the neighbouring cells in their immediate surroundings through their regenerative secretome with anti-inflammatory properties (1,4,5).
Who?
Carl Joseph Eberth and Charles Rouget are often credited as the first authors to describe pericytes in the 19th century. However the interest in this cell type has risen only in the last decade, due to their role in neurovascular coupling and cerebral blood flow deficits following cerebral ischemia and Alzheimer’s disease. In an in vivo glioblastoma (a very aggressive type of brain tumour) mouse model, pericytes deficient in a specific autophagy form, chaperone-mediated autophagy (CMA), presented the capacity and were sufficient to promote the elimination of glioblastoma cancer cells, by developing a pro-inflammatory phenotype that destabilizes the physical tumour cell interactions, increase the secretion of anti-tumour immune proteins and their ability to phagocytose tumour cell debris and present specific antigen to promote anti-tumour T cell responses (6,7).
When?
Pericytes are CD146+CD34- population isolated together with MSC from the vascular fraction of adipose tissue or other tissues (8). The manipulation of their CMA activity could be useful in the development of anti-tumour cell-based therapies for Glioblastoma treatment, provided that this type of cells is able to cross the BBB and reach tumour areas upon intravenous injection (7).
Where?
Currently, pericytes can be sourced from different suppliers, although for research use only. These include:

How? 
Pericytes are found in micro-vascularized tissues, such as the brain, placenta, retina, adipose tissue, spinal cord, lungs, breast, liver and kidneys. They can be isolated from microvessel-enriched fraction of disintegrated tissue by enzymatic digestion or microdissection techniques (9,10).

Did you know that… 
Pericytes are the known rouget cells within the capillary basement membrane with projections protruding to enwrap the vessel wall (11) which are well known as hepatic stellate cells (HSCs) in the liver (12). Pericytes are attracting interest in the field of tissue engineering due to their MSC characteristics and multiple roles in tissue repair (8).

References

  1. Gaceb A, Barbariga M, Özen I, Paul G. The pericyte secretome: Potential impact on regeneration. Biochimie. 1 de diciembre de 2018;155:16-25.
  2. Török O, Schreiner B, Schaffenrath J, Tsai HC, Maheshwari U, Stifter SA, et al. Pericytes regulate vascular immune homeostasis in the CNS. Proceedings of the National Academy of Sciences. 9 de marzo de 2021;118(10):e2016587118.
  3. Salinas MD, Valdor R. Chaperone-Mediated Autophagy in Pericytes: A Key Target for the Development of New Treatments against Glioblastoma Progression. International Journal of Molecular Sciences. enero de 2022;23(16):8886.
  4. Birbrair A, Zhang T, Wang ZM, Messi ML, Olson JD, Mintz A, et al. Type-2 pericytes participate in normal and tumoral angiogenesis. American Journal of Physiology-Cell Physiology. 2014;307(1):C25-38.
  5. Courtney JM, Sutherland BA. Harnessing the stem cell properties of pericytes to repair the brain. Neural Regeneration Research. 2020;15(6):102-2
  6. Valdor R, García-Bernal D, Riquelme D, Martinez CM, Moraleda JM, Cuervo AM, et al. Glioblastoma ablates pericytes antitumor immune function through aberrant up-regulation of chaperone-mediated autophagy. PNAS. 2019;116(41):20655-65.
  7. Molina ML, García-Bernal D, Salinas MD, Rubio G, Aparicio P, Moraleda JM, et al. Chaperone-Mediated Autophagy Ablation in Pericytes Reveals New Glioblastoma Prognostic Markers and Efficient Treatment Against Tumor Progression. Frontiers in Cell and Developmental Biology. 2022;10.
  8. Wang Y, Xu J, Chang L, Meyers CA, Zhang L, Broderick K, et al. Relative contributions of adipose-resident CD146+ pericytes and CD34+ adventitial progenitor cells in bone tissue engineering. npj Regen Med. 2019;4(1):1-9.
  9. Valdor R, García-Bernal D, Bueno C, Ródenas M, Moraleda JM, Macian F, et al. Glioblastoma progression is assisted by induction of immunosuppressive function of pericytes through interaction with tumor cells. Oncotarget. 2017;8(40):68614-26.
  10. Alvino VV, Mohammed KAK, Gu Y, Madeddu P. Approaches for the isolation and long-term expansion of pericytes from human and animal tissues. Front Cardiovasc Med. 2023;9:1095141.
  11. Attwell D, Mishra A, Hall CN, O’Farrell FM, Dalkara T. What is a pericyte? J Cereb Blood Flow Metab. 2016;36(2):451-5.
  12. Kostallari E, Shah VH. Pericytes in the liver. Adv Exp Med Biol. 2019;1122:153-67. 


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