To repair a damaged heart, three cells are better than one

Date:
September 15, 2020
Source:
San Diego State University
Summary:
CardioClusters use three types of cells to reduce scar tissue and
improve function by integrating into and persisting within damaged
heart tissue.



FULL STORY ==========================================================================
Cell therapy for cardiac regeneration, while promising, has been hampered
by issues with long-term survival of the transplanted cells. Now, a
technique that combines three different types of cells in a 3D cluster
could improve its efficacy in reducing scar tissue and improving cardiac function after a heart attack.


========================================================================== Called CardioCluster, the bioengineering technique was developed by
Megan Monsanto, a recent doctoral candidate who worked with Mark Sussman, distinguished professor of biology at the San Diego State University Heart Institute. They found there is strength in numbers, even in cell therapy.

Their research shows the cell clusters improve heart function because
they have much better retention rates compared to single cell injections
-- the clusters persisted inside the heart walls of mice models for as
long as five months after transplantation, a significant advancement.

As a master's student in bioengineering at SDSU, Monsanto became very interested in tissue culture of cells for cardiac research. This led her
to Sussman, a molecular biologist and longtime principal investigator
at the institute.

When she learned about the challenges in getting injected cells to
persist and survive inside the heart walls, she came up with the idea
of a 3D cluster of cells that would interact with each other and stick together. But even she was surprised at how long they survived as
a cluster.

"At 20 weeks we were still able to see the cells," Monsanto said. "Our
design takes advantage of the inherent beneficial attributes of
three distinct cardiac cell types, each known to possess beneficial
properties that blunt heart disease in their own unique way." The cluster combination she arrived at after extensive research comprises mesenchymal
stem cells which help communicate and support other cells, endothelial progenitor cells which line the insides of blood vessels, and cardiac interstitial cells which are key to forming cardiac tissue. The study
was published in Nature Communications in August.



========================================================================== Working in the Sussman lab with human heart cells surgically implanted
into the hearts of immune-compromised mice, she genetically modified the transplanted cells to express a fluorescent tag to enable tracking. Each
cell type has a different tag or color, so weeks later when she tracked
them, all three color tags were consistently found by confocal microscopy imaging.

One reason for their high rates of retention and longevity is that they
were cultured together before injection, and this familiarity maximizes cell-to-cell interaction.

"When you need to go into a bad neighborhood, it's better to go with
some friends," Sussman explained. "Since these cells talk to each other,
they support each other when they enter the hostile environment of the
damaged heart." CardioClusters closely mimic the natural environment
within the human body much better than 2D cultured single cells that
are easily pumped out of the heart.

Their larger surface area as a cluster helps with retention.

"The tougher cells naturally go to the outside while protecting the
slower growing cells in the center," Sussman said. "The cells seem to
know what to do and they spontaneously figured out how to assemble within
the cluster." When Monsanto subjected the cluster cells to stress tests,
the outer cells survived better. But when tested separately, about 50%
of the cardiac interstitial cells died.



==========================================================================
Each cell type within the cluster plays a specific role -- the mesenchymal
stem cells are the glue, the cardiac interstitial cells are the brain,
and the endothelial progenitor cells are the highway on which nutrients
travel which keeps the cluster alive, she explained.

The clusters can be modified and optimized for different needs, and cell
ratios can be tweaked, which will form the next step in their research.

"While there are many who are skeptical of cardiac cell therapy, it's
important to try innovative approaches like CardioClusters to build upon
what we have learned and improve outcomes rather than becoming frustrated
and giving up," Sussman said.

"For more than a decade, a major limitation of cell therapy has been
that the cells don't stick around so the effectiveness of treatment is
lost. With this approach, we get significantly better recovery and repair,
and we are able to see the cells months later, which is groundbreaking."

========================================================================== Story Source: Materials provided by San_Diego_State_University. Original written by Padma Nagappan. Note: Content may be edited for style and
length.


========================================================================== Journal Reference:
1. Megan M. Monsanto, Bingyan J. Wang, Zach R. Ehrenberg, Oscar
Echeagaray,
Kevin S. White, Roberto Alvarez, Kristina Fisher,
Sharon Sengphanith, Alvin Muliono, Natalie A. Gude, Mark
A. Sussman. Enhancing myocardial repair with CardioClusters. Nature
Communications, 2020; 11 (1) DOI: 10.1038/s41467-020-17742-z ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/09/200915110005.htm

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