Pericytes are specialized cells that help structure and regulate the body’s smallest blood vessels. Their wide-ranging roles in health and disease make them a subject of intense scientific interest. However, accurately identifying these cells has been a persistent challenge. This difficulty led to the development of methods to distinguish them from other cells they closely resemble, known as pericyte markers, which are fundamental to studying these versatile cells.
What Are Pericytes and Why Are They Difficult to Identify?
Pericytes are mural cells, meaning they are part of the wall of blood vessels, specifically wrapping around capillaries and other microvessels. They possess a distinct cell body and long, branching cytoplasmic arms that make direct physical contact with the endothelial cells forming the vessel tube. This intimate association allows them to perform several functions, including regulating blood flow, maintaining the stability of blood vessels, and contributing to the integrity of barriers like the blood-brain barrier. Pericytes are also involved in the formation of new blood vessels (angiogenesis) and contribute to tissue repair.
Historically, identifying pericytes has been challenging. Their location, embedded within the vessel’s basement membrane, places them in close proximity to other perivascular cells like smooth muscle cells and fibroblasts, making visual distinction difficult. Early identification relied on microscopy, which could not always reliably separate pericytes from these other cell types based on appearance alone.
The challenge is compounded by the fact that pericytes are not a uniform population. Their characteristics and density can vary significantly depending on the organ, the specific type of blood vessel, and the body’s physiological state. This heterogeneity means that a pericyte in the brain might look and act differently from one in the skeletal muscle. This variability makes it hard to establish a single method for identification based on morphology alone, highlighting the need for molecular identifiers.
Defining and Identifying Pericyte Markers
A cell marker is a molecule, typically a protein, that is consistently found on a specific type of cell, allowing it to be distinguished from others. Pericyte markers are the specific molecules scientists use to reliably identify pericytes and separate them from the diverse cell populations surrounding blood vessels. Because no single marker is exclusive to all pericytes, researchers often use a combination of markers for accurate identification.
Several molecules are used as markers, though their presence can vary, underscoring why using a panel of markers is a common strategy. Frequently used markers include:
- Proteoglycan NG2 (also known as CSPG4), which is often present on developing or active pericytes.
- Platelet-Derived Growth Factor Receptor-β (PDGFRβ), a receptor involved in recruiting pericytes to blood vessels.
- CD146, an adhesion molecule, and Regulator of G-protein Signaling 5 (RGS5), a protein involved in cell signaling.
- Alpha-Smooth Muscle Actin (α-SMA) and desmin, muscle-associated proteins whose presence can vary. For instance, pericytes on capillaries may not express α-SMA, while those on arterioles often do.
The Significance of Pericyte Markers in Research and Medicine
The ability to accurately identify pericytes using molecular markers has been transformative for research and medicine. These tools allow scientists to visualize pericytes within tissues, isolate them for laboratory experiments, and investigate their functions. By tagging these cells, researchers can observe how pericytes contribute to vascular development, blood-brain barrier maintenance, and tissue healing.
In medicine, pericyte markers are important for understanding how these cells contribute to various diseases. In diabetic retinopathy, the loss of pericytes from retinal capillaries is an early event. In cancer, pericytes are involved in building the new blood vessels that tumors need to grow. Markers help researchers study these processes and identify pericytes as potential therapeutic targets.
Pericytes are also implicated in fibrosis, where they can transform into scar-producing cells, and in neurological disorders like Alzheimer’s disease and stroke. The use of markers helps clarify the role of pericytes in these conditions and opens the door for developing therapies aimed at modulating pericyte behavior to improve patient outcomes.
Limitations and Nuances of Pericyte Markers
Despite their utility, current pericyte markers have limitations. The most significant challenge is the lack of a single, universal marker that can identify every pericyte in every tissue and under all conditions. This issue stems from the inherent heterogeneity of pericytes, as they express different proteins depending on their location and whether the tissue is healthy or diseased.
Marker specificity further complicates identification. Many proteins used to identify pericytes are not exclusive to them and are also expressed by other cells, such as vascular smooth muscle cells and fibroblasts. For example, PDGFRβ is a common pericyte marker but is also found on fibroblasts, which can lead to misidentification if it is used in isolation.
To overcome these challenges, the standard approach is to use a panel of multiple markers simultaneously. By confirming the presence of several pericyte-associated proteins and the absence of markers for other cell types, scientists can be more confident in their identification. Marker expression can also be dynamic, changing as a cell matures or responds to injury. The ongoing search for more definitive pericyte markers remains an active area of vascular biology research.