Good text. Opportunities and five challenges for stem cell therapy for heart disease.

Guide: At present, hpSC-CMs have made substantial progress in clinical treatment, but its potential molecular mechanism is still in the fog.
heart is one of the most important organs in human beings, and its role is to pump blood into all parts of the body to give us the power of life.
because of the specificity of heart tissue, humans can be protected from "heart cancer", but all kinds of cardiovascular diseases make us helpless.
recently, stem cell journals published a review summarizing the latest advances and clinical application challenges in heart disease therapy, heart model building, and drug development in human erythmatic stem cell-derived cardiomyocytes (hPSC-CMs).
authors believe that hPSC-CMs have made substantial progress in clinical treatment, but their potential molecular mechanisms are still in the fog.
has so far solved the mystery of human erythrial stem cells, the only reliable source of human heart muscle cells is human erythebic stem cells, including embryonic stem cells and induced erythmatic stem cells.
stem cells are crucial to the development of regenerative medicine.
patients can directly use their own blood cells, skin cells, after recoding into induced erythmic stem cells, and eventually differentiated into myocardial cells, nerve cells and any other desired regenerative cells.
in general, this stem cell therapy not only compensates for the ethical shortcomings of embryonic stem cells, but also greatly reduces the risk of immune rejection.
's cardiac regeneration capacity is limited, what are the "strange tricks" of stem cells? Adults have limited ability to regenerate the heart, and after myocardial infarction often results in the loss of myocardial cells or their replacement by fibrosis tissue, which can eventually lead to fatal heart failure.
studies have shown that injecting human embryonic stem cell-induced myocardial cells into the heart muscle can improve and reshape isotromic myocardial function in rats 7-10 days after the death of myocardial isoemia and then perfusion damage or permanent myocardial infarction.
same time, the researchers found the same results when they injected human-induced obstructive stem cell-produced myocardial cells into rodent infarction models.
, human embryonic stem cell-induced heart muscle cells can also electrically couple to suppress arrhyth arrhythmics in the heart of injured guinea pigs.
Clinically from 2002 to the present, there have been many cases of stem cells to treat heart disease, such as: TOPCARE-DCM, CardiAMP and other clinical trials, most clinical trials are currently focused on bone marrow-filled stem cells through coronary infusion, self-source or interstitial stem cell transplantation to treat cardiovascular disease.
is a erypotent stem cell with all the commonalities of stem cells, i.e. self-renewal and multi-way differentiation.
is currently the most widely studied in clinical applications, such as combined with hematopoietic stem cells, which can improve the success rate of transplantation and accelerate hematopoietic reconstruction.
recent years, interstitiogenic stem cells have made major clinical breakthroughs in solving various blood system diseases, cardiovascular diseases, cirrhosis, neurological diseases and autoimmune diseases, saving the lives of more and more patients.
electroscopic diagram of myocardial cells injected into the heart of rats with human-induced erythmatic stem cells (1) The five challenges of cardiomyopathic stem cell therapy have not only made substantial progress in the expected application of cell replacement and cellless therapy, but have also been effective in treating heart disease or hereditary heart disease caused by abnormal physiological damage.
, however, the functional development and maturation of human pluripotent stem cells are complex, their potential molecular mechanisms are not yet fully clear, and the electrophysiological mechanisms in cells still need to be studied in depth.
there are five main challenges in heart stem cell therapy: 1. The quality of stem cells.
example, there are differences in the expression of exons of myocardial cells (hESC-CMs)/iPSC-sourced cardiomyocytes (hiPSC-CMs) from embryonic stem cell sources under hypoxia conditions.
Therefore, we need to strictly control every step of cell production, including cell production, cell line selection, and genomic stability testing;
addition, new methods are needed to reduce the heterogeneity of cells in terms of mass, subtype and maturity levels.
2. Maturity of myocardial cells.
that stem cell transplants perform better on the 20th or 30th day of differentiation than on the 8th or 30th day.
the maturity of the cells affects proliferation and treatment after they are moved into the host heart, and implanting immature cells into the adult heart can lead to arrhythmic arrhythmics.
Researchers promote the maturation of human omnicric stem cell-derived heart muscle cells through extracellular substitutation, cell arrangement techniques, electrical stimulation, mechanical stretching, mitochondrial engineering, and microRNAs and hormone interventions, but they have not yet reached the maturity of adult heart muscle cells, so effective cardiac stem cell therapy also needs to carefully adjust the optimal maturation of stem cells to balance cell survival and risk of arrhythmic disorders after transplantation.
3. Cell survival rate.
Cell survival and long-term retention are important reasons hindering cell therapy, in order to solve this problem, the researchers suggest that cells can be pretreated before transplantation to enhance their resistance, the joint application of supportive biological materials, manipulation of the local immune environment of the infarction heart to optimize the host tissue to receive transplants and other methods to solve the problem.
4. Risk of arrhyth arrhythmics.
at different maturity levels may have varying degrees of functional coupling, hetero-activation, and regional conduction, and produce abnormal pulses.
Therefore, in future large-scale animal studies, it is important to test the feasibility of a variety of anti-arrhythmic methods, including determining suitable cell surface markers to prepare high-purity stem cells, determining appropriate transplant maturity, fine-tuning the number of transplanted cells, and using them in combination with anti-arrhythmic drugs.
5. Exclusive reaction.
immune rejection is one of the stumbling blocks of cardiacial stem cell therapy, and this problem is also a hot topic in immunology.
study showed that in large animals receiving stem cell therapy for heart disease, the use of immunosuppressive drugs reduced part of the animal's immunity, as well as some side effects.
human erythroid stem cells derive myocardial cells that produce an immune rejection response through an adaptive immune system mediated by the main tissue-compatible complex, the human white blood cell antigen system.
researchers found that the immune rejection response of foreign cells could be significantly reduced by fine matching of the main tissue-compatible complex cells and the subject cells in Category I.
, the relevant biolibrary hPSC system with extensive diversity of human le white blood cell antigens, the universal and immune-compatible supply hPSC system is also being further developed. The application of
human cynic stem cell-derived myocardial cells in heart disease modeling and repair Looks ahead to the current, many clinical trial results show that stem cells are effective in treating all types of heart disease, heart stem cell therapy has great potential in alleviating patients' conditions, prolonging patients' life and improving patients' quality of life, and more researchers are also involved in the study of cardiac stem cell therapy.
, however, there are also great challenges and many problems that need to be addressed in the clinical application of cardiac stem cell therapy, and as these challenges are overcome, it is believed that stem cell therapy for heart disease will benefit more patients in the future.
References: 1. Heart regeneration using pluripotent stem cells.#fig00052. Perspective on human pluripotent stem cell-derived cardiomyocytes in heart disease modeling and repair.