Exploring the Role of Pericytes in Disease and Healing

Exploring the Role of Pericytes in Disease and Healing


The vasculature tissue consists of different types of cells: smooth muscle cells, endothelial cells, connective tissue cells, and pericytes (Johnson et al., 2002). Pericytes were discovered by Charles Marie Benjamin Rouget, a French physiologist, 140 years ago (Herndon et al., 2017). Pericytes are present in every vascularized body tissue and cover 22 to 99 % of the endothelial surfaces. Even though the discovery of pericytes happened early, their role was not clearly understood. Even today, the questions of ‘what are pericytes’ and ‘role of pericytes in blood vessel formation’ bewilder scientists and biomedical researchers alike. However, new research insights about pericytes and their interaction with other cell surface markers have shed light on their role in disease and healing (Bergers and Song, 2005).

What are Pericytes?

Pericytes are a heterogeneous population of cells lining the endothelial surfaces of blood vasculature. These cells display variability in ontogeny, localization, and morphology, besides having stem cell properties. Pericytes have been reported to differentiate into adipocytes, osteoblasts, chondroblasts, and smooth muscle cells (Bouacida et al., 2012). Pericytes are important in maintaining a healthy vasculature by building a functional unit along with endothelial cells to regulate microvascular stability (Kelly-Goss et al., 2014). Pericytes also play crucial roles in regulating blood flow, angiogenesis, wound healing, and maintaining blood-brain barrier permeability (Armulik et al., 2011).

As per-flow cytometry analysis, pericytes CD146 markers and commonly express surface proteins like SMA, Desmin, NG2, and PDGFR-β, like other cells at the same anatomical location (Kelly-Goss et al., 2014) (Gerhardt and Betsholtz, 2003). In the case of pericytes, researchers suggest that different tissue locations have an impact on cell function and phenotype.

Role of Pericytes in Blood Vessel Formation and Maintenance

As per research reports, pericytes are duly associated with blood vessel stabilization and blood flow maintenance. Pericytes can also produce vasoconstriction and vasodilation in capillary vessel beds to regulate the vascular diameter and blood flow (Rucker et al., 2000). These cells interact not only with the endothelial cells but also with immune cells and hematopoietic cells. Pericytes are crucial regulators of hematopoiesis (Itkin et al., 2016) and upon endothelial balance disruption, pericyte dysfunction can lead to pathological conditions by affecting the blood vasculature in cases of diabetic retinopathy (Chou et al., 2014) and cancer (Bergers and Song, 2005).

Role of Pericytes in the Retina

Loss of pericytes has been suggested to hamper blood vessel remodeling, and possibly cause abnormalities of the eye. This is observed in the case of diabetic retinopathy (Beltramo et al., 2013). Several reports suggest that vascular endothelial cells release PDGFB to recruit PDGFRβ-expressing pericytes in order to facilitate stabilization during blood vessel development (Sweeney et al., 2016). A study report also demonstrates that PDGFB/PDGFRβ signaling is indispensable when it comes to the formation and maturation of the blood-retinal-barrier through active pericyte recruitment onto growing retinal vessels (Park et al., 2017). The study further suggests that pericytes are important in the adult retina also in the form of regulators by controlling the expression of FOXO1, Ang2, and VEGFR2 genes for protecting retinal vessels against stress and injuries.

Role of Pericytes in Cancer

Pericytes play a very crucial role in regulating the tumor microenvironment. Due to their potential of angiogenesis, pericytes take part in tumor neovascularization and blood vessel stabilization. Pericytes are present in the tumor microenvironment, for the stabilization of new blood vessels. Pericytes, present in the tumor microenvironment, show different features than the normal pericytes. This suggests that there is a tumor-associated pericyte population that corresponds with deregulated vascularization in the case of cancers. New studies have shown the role of anti-pericyte agents along with anti-cancer agents as a beneficial strategy to inhibit cancer progression, as killing off the pericyte population in the tumor microenvironment prevents angiogenesis and limits metastasis (Birbrair et al., 2014).

Role of Pericytes in Healing

Besides playing a role in diseases, pericytes also play a crucial role in tissue development, regeneration, and healing (van Dijk et al, 2015). When endothelial cells migrate to new tissue during angiogenesis, healing pericyte populations lead the way and subsequently mature into cells of different specificities, as seen during bone development or bone injuries where pericytes express osteoblast-like features (Ono et al., 2014). Scientists have taken this regenerative potential of the pericytes into account when it comes to devising the strategies for tissue regeneration in case of tissue-damaging disorders (Herrmann et al., 2016).

Current Pericyte research is strongly focusing on identifying pericyte-associated pathological processes and new drug targets. A good understanding of the diverse pericyte population and their functions can give better insights into the communication between pericytes and other body cells, leading to discoveries of new therapies. For more information on culturing primary cells, visit https://kosheeka.com/

 

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