Stem cell therapy may help mend a broken heart staff (2014). “Medical gallery of Blausen Medical 2014

Dilated cardiomyopathy (DCM), a condition where the muscles of the heart are weak and can lead to heart failure, is considered rare in children. However, because the symptoms are not always easy to recognize the condition can go unnoticed for many years, and in severe cases can damage the heart irreparably. In that case the child’s only option is a heart transplant, and a lack of organ donors means that is not always available.

Now, new research out of Japan – published in the journal Science Translation Medicine – could lead the way to new treatments to help children avoid the need for a transplant.

In the study, researchers at Okayama University used heart stem cells called cardiosphere-derived cells (CDCs) to try and repair the damage caused by DCM.  

In a news release, lead researcher Professor Hidemasa Oh, says previous work has shown that because CDCs have the ability to turn into heart tissue they have the potential of reversing damage, but it’s not clear if this would work in children.

“I have been working on cardiac regeneration therapy since 2001. In this study, my team and I assessed the safety and efficacy of using CDCs to treat DCM in children.”

Tests in animal models with DCM showed that the CDCs resulted in a thickening of the heart muscle leading to increased blood flow around the body. This increased blood supply helped repair damaged tissue. Based on this trial the researcher determined what might be a suitable dose of CDCs for children with DCM and were granted permission to carry out a Phase 1 clinical trial.

Five young patients were treated and the results were cautiously encouraging. After a year none of the patients had experienced any severe side effects, but all had indications of improved heart function.

The study also gave the researchers some strong clues as to how the therapy seem to work. They found that when the CDCs were transplanted into the patient they secreted exosomes, which play an important role in cells communicating with one another. These exosomes then helped create a series of actions within the body; they blocked further damage to the heart tissue and they also helped kickstart the repair process.

The Okayama team are now hoping to carry out a Phase 2 clinical trial with more patients. Ultimately, they hope to be able to see if this approach could help prevent the need for a heart transplant in children, and even adults.

One thought on “Stem cell therapy may help mend a broken heart

  1. Exosomes are nanoscale lipid bilayer vesicles mediate cell-cell communication and transferring distinction payload of microRNA (mRNA) and other non-coding RNA specific to the parents cell types. The content of exosomes are a rich source of cytosolic proteins, lipids and nucleic acid (miRNA) and various cells released exosomes to mediate intracellular signaling and communication via cargo. Exosomes from cardiac myocytes or stem/progenitor cells can promote cardiac repair and regeneration. For instance, CDC-derived exosomes can modify the content of exosomes secreted by recipient fibroblasts leading to amplify therapeutic effect of decreasing scar content by increasing the amount of fibroblasts and collagen degradation but reducing collagen production. Exosomes released by CDC can replicate cardioprotective, cardiac regenerative properties and improve heart function in a variety of cardiac diseases . Thus, exosomes from donor cells induce subsequent physiological changes in recipient cells through binding to specific receptors, fusion of membranes and release of their cargo. Several studies showed that human CDC-derived exosomes can reduce acute ischaemia-reperfusion injuries, half chronic post-MI adverse and remodelling in pigs when delivered by IM injection. Exosomes are acellular, do not instigate major immune response and secret many paracrine factors to reduce local inflammatory reaction and infiltration of inflammatory cells in the recipient. Therefore, the used of CDC-derived exosomes in human is likely to be safe. Immune response mediated by immune cells play important and complicated roles in progression of various cardiovascular diseases such as MI and atherosclerosis. The exosomes derived from immune cells have shown pleiotroplc effects in the pathological state, whether similar to or different from their parents cells. T cells like professional antigen-presnting cells interact and release exsomes with heterogeneous characteristics. These vesicles can targeted to different sort of immune cells and modify their function. They act like antigen-presenting vesicles involved in stimulating T/B cells to induce either cellular adaptive immunity or humoral immunity. For instance, MI required intense but transient inflammatory response and triggered by MI essential for cardiac repair, clear the infarcted area of dead cells and extracellular matrix debris. The exists of sophisticated regulation of the balance between inflammatory reaction and repression of inflammation prepared the infected area for subsequent proliferation phase of healing. Thus, immune cells are paramount importance to cardiac immune response, they rather than injured cardiomyocytes are predominant modulator of this inflammatory balance.

    However, very few studies had been reported on exosomes regulated immune response on cardiac repair. Further characterize the roles of nucleic acid of exosomes and investigate the impacts of exosomes on immune system and cardiovascular diseases may reveal an important clues to improve efficacy and safety of therapeutic in heart diseases.

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