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Credit: Mesenchymal Stromal Cell

Mobilizing mesenchymal stromal cells could promote bone formation after surgery

March 24, 2020

Scientists have examined the therapeutic benefits of mobilizing mesenchymal stromal cells in patients with orthopedic injuries
This method circumvents many of the limitations of traditional cell-based therapies and reduces both cost and time
A new study has shown that two drugs which are already FDA approved, when used in combination, can mobilize MSCs from bone marrow to blood
The group believes endocannabinoid receptors are involved in the MSC mobilization

Mesenchymal stromal cells (MSCs) are multipotent cells found in the bone marrow and fat tissue. MSCs can differentiate into different types of cells in the body, including bone. There are many therapeutic approaches currently being evaluated that involve intravenous injection or direct site injection of autologous (from the same person) or allogeneic (from the same species, i.e., a donor) MSCs to treat orthopedic injuries. MSCs are believed to release regenerative factors that aid bone formation. Now, a new study published in the journal Regenerative Medicine has looked at the possibility of mobilizing MSCs directly from the bone marrow into the blood, thereby bypassing many technical and regulatory hurdles. Researchers have conducted experiments in mice and rats and found that three drugs (beta-3AR agonist, CXCR4 antagonist, and AMD3100/ Mozobil/ Plerixafor) can accomplish this. The experiments were conducted in mice and rats. Studies have previously shown that rodents with injury have higher levels of circulating MSCs. In humans, patients of heart attack or burns have higher levels of circulating stromal cells in their blood. The scientists postulated that increasing the number of circulating MSCs could help accelerate bone formation in areas of fracture and enhance tissue regeneration in skin wounds. The idea was to identify drugs that can mobilize MSCs as a potential regenerative therapy. This would save time and money because there would be no need to harvest the stromal cells, expand the cell lines, and inject the MSCs into the patient, a process that is required in conventional cell therapy approaches. CXCR4 antagonists and AMD3100 are used to mobilize hematopoietic stem cells from the bone marrow. This treatment combination is FDA approved for patients with multiple myeloma and non-Hodgkin’s lymphoma who are poor hematopoietic mobilizers. Previously, this combination of drugs has been found to be ineffective in mobilizing MSCs from the bone marrow. However, the researchers demonstrated that pre-treatment with VEGF-A (vascular endothelial growth factor A) followed by treatment with a CXCR4 antagonist allowed MSCs to be mobilized into the blood. The use of a beta-3AR agonist BRL37344 in combination with a CXCR4 antagonist (AMD3100) was able to mobilize MSCs into the blood with demonstration of enhanced bone healing in a rodent spine fusion model. The scientists believe that the MSC mobilization is regulated through endocannabinoid receptors. The results indicate that pharmacological strategies to mobilize MSCs can be used to promote bone formation in fracture patients. What’s interesting is that this new combination treatment uses two clinically approved drugs to mobilize the MSCs and can be put to therapeutic use in patients with orthopedic injuries. The fact that these drugs are FDA approved means these findings could translate rapidly into clinical use.

References: https://www.nature.com/articles/s41536-020-0088-1#Abs1

Mobilizing mesenchymal stromal cells could promote bone formation after surgery

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