14 September 2020

One is good, but three is better

Cell therapy for heart regeneration is a promising direction, but now there are problems with the long-term survival of transplanted cells. A new method combining three different cell types into a three-dimensional cluster can increase its effectiveness in reducing scar tissue and improving cardiac function after myocardial infarction.

The bioengineered CardioCluster method was developed by Megan Monsanto and Mark Sussman of the San Diego State University Heart Institute. They have shown that even in cell therapy, quantity matters.

CardioCluster cells restore heart function better than existing methods because they have much better survival rates compared to injections of single cells: clusters were preserved inside the heart walls of mouse models for five months after transplantation, which is a significant achievement.

The cluster combination includes mesenchymal stem cells, which help communicate and support other cells, endothelial progenitor cells lining the inside of blood vessels, and cardiac interstitial cells, which are key to the formation of cardiac tissue. This design uses the advantages inherent in three different types of cells, each of which has useful properties and restores damaged heart tissue in its own way.

Working in Sussman's lab with human heart cells surgically implanted into the hearts of immune-compromised mice, Monsanto genetically modified the transplanted cells to express a fluorescent tag for tracking. All cell types had labels of different colors, and after a few weeks, the labels of all three cell types were sequentially detected using confocal microscopy.

One of the reasons for CardioCluster's high survival rates is that they were cultured together before injection, and this "familiarity" improves intercellular interaction. In other words, the cells support each other when they get into the hostile environment of a damaged heart.

CardioCluster imitates the natural environment of the human body much better than separately cultured cells that are quickly removed from the heart. The large surface area of the cluster helps the cells to stay in the heart for a long time.

The more stable cells in the CardioCluster naturally move to the surface, while protecting the slower-growing cells in the center. During stress tests, external cells survived better, but when tested separately, about 50% of interstitial heart cells died.

Monsanto explained that each cell type in the cluster plays a role: mesenchymal stem cells are the glue, interstitial heart cells are the brain center, and endothelial progenitor cells are the backbone along which nutrients that support the life of the cluster move.

Clusters can be optimized for different needs, and the ratio of cells can be changed – this will be the next step in Monsanto and Sussman's research.

Cell therapy can become a fairly effective method of treating scarring after a myocardial infarction, and the CardioCluster approach will allow for significantly better recovery of the heart.

Article by M.M.Monsanto et al. Enhancing myocardial repair with CardioClusters is published in the journal Nature Communications.

Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru according to SDSU materials: To Repair a Damaged Heart, Three Cells are Better Than One.

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