Published on : Sep 22, 2017
In a defining study exploring the contrast between the cardiac tissues regeneration capability of humans and rodents, scientist have found that the complete cardiac repair in humans may rely on the body’s innate immune system, specifically on macrophages, large white blood cells integral to our immune system. The study conducted at Mount Desert Island Biological Laboratory, Maine, U.S., was led by the scientist James Godwin. The researchers exploring the role between macrophages and fibroblasts, the cells in connective tissues that promot healing, found that fibrosis is critical to impeding the regeneration and repair of heart. Fibrosis is the natural response to heart damage in adult mammals.
Adult Salamander Macrophage-Mediated Regeneration Template for Cardiac Recovery
The study was conducted on adult axolotl or Mexican salamander, the champions of scar-free regeneration of heart tissues, other than the urodele amphibian zebrafish, since they are naturally wired to replace lost cardiac tissues. The findings highlighted that inhibiting the process through macrophage-mediated control, along with the modification of extracellular matrix (ECM) promoted the complete regeneration in them.
This finding may act as a robust template to discover a therapeutic target for improving cardiac repair outcomes in mammals, especially humans. Though, as we grow, the regenerative ability of the heart tissues is lost and is mainly attributed to the lack of cardiomyocytes, the genetic programmability is due to other features of the ECM, mainly fibrosis.
Drug Therapies Using Macrophages to Promote Cardiac Repair Outcomes
The researchers used a cardiac cryo-injury model for the Mexican salamander and induced a necrotic ischemic injury. They found that despite the activation of cardiomyocytes proliferation, macrophages leads to early ECM maturation and blocks regeneration. Thus, the depletion of macrophages have been found to impede fibrosis. Cardiomyocytes that play a crucial role in the repair of heart muscles.
The investigators believe that the results will useful in designing drug therapies using macrophages to promote heart regeneration or to induce genetic programming to promote scar-free cardiac repair. Though, progressive scarring inhibits the functionality of macrophages, it isn’t yet clear that the scarring is the only factor responsible for preventing regeneration. At present, the team is is actively looking for these drug targets.