Repairing the injured heart — Regenerative medicine takes another step forward
Think heart failure is incurable? Think again. Regenerative medicine could restore an injured heart – just by an injection to the heart.
Regenerative medicine is an increasingly popular field in the health sciences. Whereas traditional regenerative medicine looked at embryonic stem cells, more and more researchers are investigating adult pluripotent stem cells (stem cells deriving from adult cells). One of the advantages of using adult pluripotent stem cells is that complications arising from rejection after transplant can be avoided if a person’s own cells are used. Furthermore, some researchers are interested in reprogramming adult cells directly into another cell type without the cells having to go through stem cell stage; this prevents the unwanted possibility of stem cells forming into tumors at the site of transplant.
A team of researchers at the University of California, San Francisco, is trying to apply regenerative medicine to treat heart failure. Despite intensive investigation in the development of better treatment, heart disease remains the leading cause of deaths worldwide, affecting 14 million people. One of the difficulties in treating heart failure is that cardiomyocytes, or muscle cells of the heart that cause the heart to beat, have little or no regenerative capability, meaning that they are permanently lost after heart attack. While cardiomyocytes do not regenerate after heart injury, non-muscle cardiac fibroblasts migrate to the injury site and start dividing there, forming a scar and decreasing the pumping strength of the heart. Fibroblasts make up over 50% of the cells in the heart. The researchers in the study hypothesize that these cardiac fibroblasts can serve as the source of cardiomyocytes in the same heart using regenerative medicine.
The study involved inducing heart injury in mice, after which the mice received treatment that allows their existing cardiac fibroblasts to be converted into cardiomyocyte-like cells. This reprogramming of cardiac fibroblasts was done by locally injecting retrovirus at the site of the heart injury. The retrovirus infection delivers genes for specific cocktail of transcription factors that turn fibroblasts into cardiomyocyte-like cells.
The cardiomyocyte-like cells resulting from reprogramming cardiac fibroblasts behaved similarly to native cardiomyocytes. Not only did they express proteins found in cardiomyocytes, but they were also able to perform cell-cell communications with neighboring cells, showing that they are fully integrated into the heart tissue. Moreover, these cells were able to contract in response to electrical stimulation, which is the normal function of cardiomyocytes – causing the heart to beat and pump blood. Importantly, mice treated with fibroblast reprogramming treatment after heart attack showed significant improvement in the performance of the heart within 8-12 weeks and up to 3 months (which was the duration of the study).
The study demonstrates promising results, but it is still not ready for real application. Reprogramming efficiency of fibroblasts in the study was only about 12%. The gene delivery method needs optimization in order to increase the efficiency of converting fibroblasts into cardiomyocytes. Also, even though viral infection is already often used in gene therapy, alternative method might be preferred by patients – afterall, injecting yourself with active virus may not be the safest thing to do. Regardless of the remaining issues that need to be solved, the authors of the study are hopeful that by tweaking out the reprogramming efficiency, they will be able to achieve greater improvement in the injured heart. As a matter of fact, a new study published this week has managed to increase the reprogramming efficiency by including an extra component in the transcription factor cocktail. The new study also demonstrated an improved heart performance following regenerative treatment in mice with heart injury compared to those not receiving the treatment.
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If you enjoyed this post, you may also enjoy my earlier post about using regenerative therapy for hair growth.