The Homing of Stem Cells

For a long time, people have not been very clear about the concept of stem cell homing, only know that there is this concept. Returning to the nest, which nest to return to? Is it attributed to the injury or to a specific organization? What is the mechanism of homing? What are the benefits of homing? Today, Mr. Bubu will teach you how to talk about the homing of stem cells without making mistakes.

Stem cells can find their own "home" by themselves, and this home is a place suitable for her own survival, just like an old horse who knows the way, always knows where her home is. This is what we call "homing". They can come out of their homes and "walk" around in the peripheral blood, and then find and enter a "niche" with a suitable microenvironment and settle in it to live and work in peace and contentment.

From the word "homing"

To fully understand the homing of stem cells, we first need to know how the term came about.

Concept: homing

"Homing" (homing) originally refers to the tendency of lymphocytes circulating in the blood to migrate to the site of lymphocytes from which , such as lymph nodes. This regression phenomenon is called "lymphocyte homing", which means It was proposed by Gallation in 1983 [1] . Later, the concept of "homing" was gradually extended to stem cells.

Stem cell homing refers to the process in which endogenous or exogenous stem cells can migrate in a directional direction under the action of various factors, cross vascular endothelial cells to target tissues and colonize and survive, similar to the migration of a large number of white blood cells to the target tissue after a local inflammatory response in the human body. Inflammation around.

Concept: stem cell niche

The cells around the stem cells form a cradle-like environment to protect the stem cells, which is called the microenvironment (stem cell nest, niche). Niche not only provides nutrients to stem cells, but also guides the actions of stem cells and determines the direction of stem cell differentiation. The microenvironment is composed of various cells adjacent to stem cells, extracellular matrix (extracellular matrix, ECM) and various cytokines.

Homing of stem cells

In addition to hematopoietic stem cells, the homing of stem cells mainly refers to mesenchymal stem cells. In 2009, Krap et al. [2] proposed to define "mesenchymal stem cell homing" as the process in which MSCs are captured in the vasculature of the target tissue and then migrate across the vascular endothelial cells to the target tissue. A large number of studies have found that when the body is ischemic, hypoxic, or injured, MSCs in the body or exogenously have the characteristic of preferential distribution to the injury site. Homing is the key to the safe and effective clinical application of MSCs.

Changes in the microenvironment are the initiating factors for the homing of MSCs, and various signaling molecules such as chemokines, adhesion factors, and growth factors are expressed locally in tissue damage. Different microenvironments secrete different signaling molecules to attract MSCs to reach the tissue. Stem cells home, and finally home to the bone marrow, home to various organs, home to inflammation and trauma sites, and even home to tumor sites.

Member of Stem Cell Homing Group

The homing mechanism of stem cells is still unclear. In short, certain specific signaling molecules bind to corresponding receptors on the MSCs membrane to jointly drive their homing behavior. The successful homing of transplanted stem cells to the microenvironment requires that the signaling molecules at the injury site be consistent with the surface receptors of MSCs, which is also one of the factors that determine the success or failure of MSCs transplantation. There are many group members involved in homing behavior, such as chemokines, growth factors and adhesion molecules.

Chemokines: mainly responsible for moving from far to near.

Specific tissues secrete specific chemokines, and through the concentration gradient of chemokines, cells with chemokine receptors are attracted to the tissue.During injury, different tissue cells can release different chemokines, which can promote the migration of MSCs. Taking the CXCR4 receptor as an example, it generally only binds to CXCL12. Bone marrow contains more CXCL12 chemokines, so CXCR4 receptors can often be found in hematopoietic stem cells in bone marrow [ 3] . In general, chemokine receptors can sense the concentration of chemokines in the external environment and guide cells to places with higher concentrations of chemokines [4] .

Legend: Chemokine exchange between bone marrow, blood and surrounding tissues during inflammation. [4]

Adhesion molecules: mainly responsible for the outside-in.

MSCs in blood vessels adhere to the capillary wall and homing to target tissues across the endothelial cell layer. MSCs and extracellular matrix bind to cell adhesion molecules by expressing cell adhesion molecule ligands, mediating the homing of stem cells to specific targets.

In addition, inflammatory factors ( such as TGFα, etc. ) and growth factors ( such as HGF, etc. ) are also important members of the homing group.

Homing rate problem

MSCs can selectively home to injury sites in various tissues, and it is important to increase the homing rate of stem cells. Using various measures to improve the efficiency of stem cell homing will improve the effect of stem cell transplantation.

Pretreatment of MSCs: Repeated passage of MSCs will lead to the loss of its stemness, which will affect its therapeutic effect. The aging of MSCs in vitro and the accumulation of oxidative damage among cells weakened the proliferation and homing potential of cells.

Transplantation of MSCs: At present, the most important transplantation methods of stem cells are arterial transplantation, vein transplantation, and local injection transplantation. Intravenous reinfusion often occurs venous obstruction in the lungs and affects the curative effect, but the advantage is that the operation is simple; arterial injection is complicated, with large trauma and bleeding; local injection has a high homing rate and good curative effect.

Adhesive and adherent processing of MSCs: Adhesion to the wall is a prerequisite for transplanted stem cells to survive, survive and be effective. Studies have found that making MSCs in an adherent and adherent state before transplantation is conducive to cell survival and homing to the target tissue after transplantation. Therefore, the effect of MSCs in the culture period is better than that of MSCs just after recovery.

Transplantation time and quantity of MSCs: Transplantation time and quantity affect the homing effect, the earlier MSCs cells , the higher the homing rate after transplantation. If the quantity is sufficient, it is best not to undergo in vitro cultivation. Rombouts et al . [5] showed that freshly isolated MSCs had a stronger homing ability than cultured and subcultured cells. The homing efficiency of MSCs can drop from 55% to 65% to 10% after 24 hours of culture, but the number of newly isolated MSCs is often scarce, and a large number of culture expansions are usually carried out in vitro to increase the number of stem cells. Therefore, there is also a contradiction between the transplantation time and the number of cells.