New bacterial proteins can help stem cells repair damaged heart tissue

Nov 29, 2019

A study has found that a surface material in stem cells could improve retention and homing on damaged heart tissues.

Adhesins, the sticky proteins in stem cells, play an important role in finding and repairing cardiac tissue. The finding paves the way for new methods to be introduced in repairing damaged heart cells.

One of the challenges in treating the aftershocks of a cardiac arrest via stem cells is finding the right location and getting them to survive long enough to begin repairs. A research team from Bristol University, spearheaded by Adam Perriman, Paul Race and other researchers, has found a method that allowed stem cells to home in on damaged areas and stay there.

The original protein was discovered by Catherine Back in 2017. The streptococcus gordonii is a microbe normally found on tooth surfaces that could bind to damaged heart tissues using sticky molecules.

The sticky protein, called CshA works via a catch-clamp mechanism, where a lasso made up of peptides readily interacts with fibronectin, a protein that shows itself in wounds. When the peptide lasso finds a myocardial fibronectin, it ‘latches’ on, and the second portion ‘clamps’ on to the target and stays there.

Using this knowledge, the group synthesized a sort of chimeric construct that fused the CshA’s gene sequence with a positively supercharged protein and expressed the characteristic onto an Escherichia coli material. After purifying via metal affinity chromatography, the group introduced the material to a molecule that had a long alkyl chain and negatively-charged carboxylate group. The negative charge held the supercharged protein, and the alkyl chain settled inside the stem cell membrane’s phospholipid bi-layer.

Perriman says that the surfactant was almost unnecessary – the interactive supercationic protein material had negative charges and was absorbed by the surrounding cells quickly, but lent a remarkable property that allowed the stem cells to persist for longer, thereby ensuring a successful clamping of the lasso and reaching the right heart tissue.

The research team then moved on to mice models after the homing construct and bindings were verified with assays. What they found there was remarkable – the stem cells’ homing propensity was increased and proved to be non-cytotoxic. Barbara Bernadim, a chemical biologist at the UK Cambridge University says that the technology used in cell delivery could be adapted for therapeutic cell delivery to other diseases and damaged organs. The group’s work could potentially open up new avenues in terms of regenerative medicine.

Netherland’s Christine Mummery at the University Medical Center of Leiden has positive remarks about the innovative delivery system and its clever makeup. As the research uses MSCs, or mesenchymal stem cells, Mummery mentions that the therapeutic value and potential should not be taken at face value and warrants further investigation.

Perriman addresses the concern, stating that the non-specific technology can be used on just about anything, or on any cell. The surfactant construct and the supercharged fluorescent protein CshA may hold other kinds of cells, including therapeutic ones. The professor jests that not all people may want to have neon green cells, so the next step is to develop the next batch of anchor regions in collaboration with Cytoseek, a spin-off company.

 

To your health,

The Healing Miracle Team

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