The recently discovered subpopulation of mesenchymal stem cells will accelerate the healing of fractures

Mesenchymal stem cells (MSCs) have tremendous potential in regenerative medicine, the goal of which is to repair damaged tissues. However, until now, not much has been known about their in vivo plasticity.

Researchers at the University of Tsukuba, Japan, have found a subpopulation of MSCs that promote bone fracture regeneration and exhibit an increased ability to differentiate into various cell types.

New mesenchymal stem cells are found in the bone marrow. They are “multipotent”, i.e., they can not only be renewed but also differentiate into various specialized types of cells, such as cells of bones, adipose, and cartilaginous tissues.

In earlier studies, scientists of the University of Tsukuba created a mouse line in which cells expressing the CD73 molecule were labeled with a green fluorescent protein for imaging. In a new study, the study of bone marrow in these animals showed that a subpopulation of MSCs expresses CD73 and sinusoidal endothelial cells (sECs), which are part of the vascular system of the bone marrow.

It was observed that MSCs expressing the CD73 molecule proliferate more actively than the CD73-negative subpopulation of MSCs and have a higher potential for differentiation into various cell types. This indicates that this group of mesenchymal stem cells may be particularly effective in bone repair. The researchers decided to study in more detail the function of CD73+ MSCs in fracture repair.

Fracture healing takes place in several stages. In the first stage, known as the Inflammatory Phase, a hematoma or a blood cell clot forms at the injury site. During the second Repairing Stage, a callus of fibrous tissue and cartilage forms in the fracture area with callus formation. Normal bone tissue replaces the callus in the third Remodeling Stage, and the bone returns to its natural shape.

“The generation of the callus is critically dependent on the recruitment of MSCs from the surrounding tissue and the bone marrow. Therefore, fracture healing models are helpful for exploring the cellular dynamics of mesenchymal stem cells migration and differentiation during tissue regeneration,” – says Kenichi Kimura, Assistant Professor at the University of Tsukuba and lead author of the study published in Bone Reports.

The researchers noticed that CD73+ MSCs move to the fracture site and form new cartilage and bone cells for healing. CD73+ sECs have also been involved in fracture healing by promoting the process of “neovascularization” – the formation of new blood vessels to support the repaired bone.

Scientists have demonstrated that transplantation of CD73+ MSCs into the fracture site markedly improved the healing process compared to the control group, which received CD73 MSCs.

Assistant Professor Kimura says: “The identification of this subpopulation of MSCs could be of great benefit for regenerative medicine and the treatment of fractures.”