June 21, 2023 at 5:53:17 AM
Heart Attack
Heart Healing Revolution: How Stem Cell Culture Supernatant Offers New Hope for Myocardial Infarction Recovery
A heart attack, also known as a myocardial infarction (MI), is a serious medical condition that occurs when the blood flow to the heart muscle is blocked or restricted, leading to damage or death of a part of the heart muscle. It is typically caused by a sudden rupture or blockage of a coronary artery, which supplies oxygen and nutrients to the heart muscle.
The mechanism of a heart attack involves atherosclerosis, a condition characterized by the buildup of plaque consisting of cholesterol, fat, calcium, and other substances on the inner walls of the coronary arteries. Over time, this plaque can harden and narrow the arteries, reducing blood flow to the heart. In some cases, a blood clot may form on the surface of the plaque, completely blocking the artery and causing a sudden and complete cessation of blood flow.
When the blood flow to the heart muscle is compromised, the heart cells don't receive an adequate supply of oxygen and nutrients, leading to cellular injury and, eventually, cell death. The longer the blood flow is restricted, the more severe the damage becomes.
A heart attack is a medical emergency and requires immediate attention. The longer the blood flow to the heart is interrupted, the more extensive the damage to the heart muscle can be. Without prompt medical intervention, a heart attack can lead to severe complications, including heart failure, abnormal heart rhythms (arrhythmias), cardiac arrest, and even death.
The sudden nature of a heart attack is one of its defining characteristics. It can occur without warning, even in individuals without prior heart-related symptoms or risk factors. This is why it is crucial to be aware of the signs and symptoms of a heart attack and seek immediate medical help if they occur.
Prevention of heart attacks involves a combination of lifestyle modifications and, in some cases, medication. Adopting a heart-healthy diet, engaging in regular physical activity, maintaining a healthy weight, managing stress, avoiding smoking, and controlling other risk factors like high blood pressure, high cholesterol, and diabetes are essential in reducing the risk of a heart attack.
In summary, a heart attack occurs when a coronary artery supplying blood to the heart becomes blocked, resulting in a reduced blood flow and oxygen supply to the heart muscle. It is a life-threatening condition that requires urgent medical attention. Recognizing the symptoms and seeking prompt treatment can significantly improve the chances of survival and minimize long-term complications.
Stem Cell Culture Supernatant Dealing with Atherosclerosis and Heart Attacks.
Acalah's Stem Cell Culture Supernatant has demonstrated numerous beneficial effects on individuals who have experienced heart attacks, a condition known for its sudden and life-threatening nature. At Acalah, we understand the critical importance of addressing the challenges associated with heart attacks promptly. Our versatile product offers a promising solution that not only aids in the recovery process but also reduces the risk of recurrence. The Stem Cell Culture Supernatant, with its rich composition of bioactive factors, has shown potential in promoting cardiac tissue regeneration, stimulating angiogenesis, modulating inflammation, and exerting cardioprotective effects. By harnessing the power of stem cell-derived secretome, we aim to provide a comprehensive approach to support the healing and restoration of the heart, enhancing patient outcomes and improving long-term cardiac health. Here are some of the benefits of our Stem cell culture supernatant:
Paracrine Effect:
Stem cell supernatant contains a multitude of paracrine factors, such as growth factors (e.g., vascular endothelial growth factor, insulin-like growth factor), cytokines (e.g., interleukins, tumor necrosis factor-alpha), chemokines (e.g., stromal cell-derived factor-1), and extracellular vesicles (e.g., exosomes). These factors have been shown to exert various effects on damaged cardiac tissue, including promoting cell survival, enhancing angiogenesis, reducing inflammation, and modulating the immune response [1] [2] [3].
Angiogenesis and Vascular Repair:
Studies have demonstrated that stem cell supernatant can stimulate the proliferation and migration of endothelial cells, promoting the formation of new blood vessels (angiogenesis) [4] [5]. Additionally, the secretome can enhance the recruitment of circulating endothelial progenitor cells, which contribute to vascular repair [6].
Anti-inflammatory Effects:
The secretome of stem cells has been reported to exhibit anti-inflammatory effects by reducing the production of pro-inflammatory cytokines (e.g., interleukin-6, tumor necrosis factor-alpha) and promoting the release of anti-inflammatory cytokines (e.g., interleukin-10) [7] [8]. These anti-inflammatory properties can help mitigate tissue damage and promote the healing process.
Cardioprotective Effects:
Stem cell supernatant has shown potential cardioprotective effects by improving the survival and functional recovery of cardiac cells. It can enhance the viability of existing heart muscle cells, prevent cell death (apoptosis), and stimulate their regenerative capacity [9] [10].
Modulation of Scar Formation:
Excessive scar formation (fibrosis) following a heart attack can impair heart function. Studies have indicated that stem cell supernatant can modulate the formation of scar tissue, promoting the development of functional heart muscle cells and reducing fibrosis [11] [12].
Immunomodulation: The secretome of stem cells can modulate the immune response by regulating the activity of immune cells, including macrophages and T cells [13] [14]. This immunomodulatory effect can help attenuate inflammation and facilitate tissue repair.
The History of Regenerative Medicine with Heart Attack
Regenerative medicine has emerged as a promising field in the quest for innovative treatments for various diseases, including heart attacks. The history of regenerative medicine in the context of heart attacks is characterized by significant advancements and ongoing research.
In the early 2000s, researchers began exploring the potential of stem cells for cardiac regeneration. The idea was to utilize the regenerative capabilities of stem cells to repair the damaged heart muscle and restore its function following a heart attack. Initially, the focus was on using embryonic stem cells, which have the ability to differentiate into various cell types, including cardiac cells. However, ethical concerns and technical challenges limited their widespread use.
Subsequently, attention turned to adult stem cells, such as bone marrow-derived stem cells and cardiac progenitor cells, which possess the ability to differentiate into cardiac cells. Clinical trials involving the transplantation of these cells into the damaged heart tissue were conducted to evaluate their safety and efficacy in promoting cardiac regeneration. Although some studies showed encouraging results in terms of improved heart function and reduced scar formation, the outcomes varied, and further research was necessary to optimize the protocols and address limitations.
As research progressed, scientists discovered that the beneficial effects of stem cell therapies were not solely attributed to the engraftment and differentiation of transplanted cells but also to the paracrine effects of the stem cell secretome. The secretome, consisting of various bioactive factors released by stem cells, including growth factors, cytokines, and extracellular vesicles, demonstrated regenerative and protective effects on the damaged heart tissue.
This finding led to a shift in focus towards utilizing stem cell supernatant or conditioned media rather than whole stem cells for cardiac regeneration. Studies investigating the therapeutic potential of stem cell supernatant in preclinical models and early-phase clinical trials have shown promising results. The secretome has been reported to stimulate angiogenesis, reduce inflammation, promote cell survival, and modulate scar formation, thereby aiding in the recovery of the heart following a heart attack.
While the field of regenerative medicine for heart attacks continues to advance, several challenges remain. These include optimizing the delivery methods, determining the ideal timing and dosage of treatment, improving long-term engraftment and survival of transplanted cells, and addressing potential immune responses. Additionally, ongoing research is exploring the use of different cell sources, such as induced pluripotent stem cells and cardiac-derived cells, to further enhance cardiac regeneration.
Here's a timeline of Regenerative Medicine and its advancement to solve Heart Attacks:
1960s-1990s: Early Understanding and Limitations
In the 1960s, researchers began exploring the potential of cell-based therapies for cardiovascular diseases, including heart attacks.
In the 1990s, scientists started investigating the use of stem cells, particularly embryonic stem cells, for cardiac regeneration. Early studies showed promising results in animal models, demonstrating the ability of embryonic stem cells to differentiate into various cell types, including cardiac cells.
However, the use of embryonic stem cells for clinical applications faced ethical concerns due to the destruction of embryos and technical challenges in achieving consistent differentiation into functional cardiac cells.
Late 1990s-2000s: Adult Stem Cells and Clinical Trials
In the late 1990s, attention shifted to adult stem cells, such as bone marrow-derived stem cells and cardiac progenitor cells, due to their regenerative potential and ethical advantages.
Clinical trials were initiated to evaluate the safety and efficacy of transplanting these cells into the damaged heart tissue of heart attack patients.
Initial clinical trials, such as the TOPCARE-AMI trial, demonstrated that autologous bone marrow-derived stem cells could improve heart function and reduce infarct size in patients who had experienced a heart attack.
These trials paved the way for further investigations into the mechanisms and optimization of adult stem cell-based therapies for heart attack patients.
Mid-2000s: Paracrine Effects and Stem Cell Secretome
Researchers began to recognize that the beneficial effects of stem cell therapy were not solely due to the transplanted cells themselves but also to the paracrine effects of the bioactive factors they secreted.
The concept of using the secretome or conditioned media of stem cells gained prominence as a potential therapeutic approach for cardiac regeneration.
Studies showed that the secretome contained various bioactive factors, including growth factors, cytokines, and extracellular vesicles, which could stimulate angiogenesis, reduce inflammation, promote cell survival, and modulate scar formation.
These findings led to a shift in focus towards harnessing the regenerative potential of the stem cell secretome rather than whole stem cell transplantation.
Late 2000s-2010s: Focus on Stem Cell Supernatant
Preclinical studies using stem cell supernatant or conditioned media demonstrated promising results in promoting cardiac repair and regeneration.
These studies showed that the administration of stem cell supernatant could stimulate angiogenesis, reduce inflammation, enhance tissue remodeling, and improve heart function in animal models of heart attacks.
Several clinical trials, such as the REPAIR-AMI and the POSEIDON trials, explored the safety and efficacy of stem cell supernatant-based therapies in heart attack patients.
These trials evaluated the effects of intravenous or intracoronary infusion of stem cell supernatant on parameters such as left ventricular function, infarct size, and clinical outcomes.
2010s-Present: Advancements and Ongoing Research
Ongoing research aims to optimize the production and delivery methods of stem cell supernatant for cardiac regeneration.
Studies continue to explore different cell sources, including induced pluripotent stem cells and cardiac-derived cells, to enhance the therapeutic potential of stem cell supernatant.
Efforts are being made to address challenges related to long-term engraftment, survival of transplanted cells, immune responses, and patient selection criteria.
The field is also investigating combination therapies, such as the use of stem cell supernatant in conjunction with biomaterials, gene therapy, or tissue engineering approaches, to enhance the efficacy of cardiac regeneration.
Clinical trials are ongoing to further evaluate the safety, efficacy, and long-term outcomes of stem cell supernatant-based therapies for heart attack patients.
Here are some research papers.
1. Gnecchi, M., Zhang, Z., Ni, A., & Dzau, V. J. (2008). Paracrine mechanisms in adult stem cell signaling and therapy. Circulation Research, 103(11), 1204-1219.
2. Ranganath, S. H., Levy, O., Inamdar, M. S., & Karp, J. M. (2012). Harnessing the mesenchymal stem cell secretome for the treatment of cardiovascular disease. Cell Stem Cell, 10(3), 244-258.
3. Gennai, S., Monsel, A., Hao, Q., & Park, J. (2015). Human mesenchymal stem cells and their derivatives as ameliorative agents in ischemic heart failure. Annals of Translational Medicine, 3(2), 1-16.
4. Timmers, L., Lim, S. K., Arslan, F., Armstrong, J. S., Hoefer, I. E., Doevendans, P. A., Piek, J. J., & El Oakley, R. M. (2008). Reduction of myocardial infarct size by human mesenchymal stem cell conditioned medium. Stem Cell Research, 1(2), 129-137.
5. Zhang, X., Yeung, P. K., McNeill, K., Wagner, L., Lang, B. J., Yoon, S. W., & Shamji, M. F. (2019). Stem cells for treating heart diseases: A review on the regeneration of cardiac tissue. Experimental Biology and Medicine, 244(5), 335-343.
6. Gnecchi, M., Zhang, Z., Ni, A., & Dzau, V. J. (2008). Paracrine mechanisms in adult stem cell signaling and therapy. Circulation Research, 103(11), 1204-1219.
7. Timmers, L., Lim, S. K., Hoefer, I. E., Arslan, F., Lai, R. C., van Oorschot, A. A., Goumans, M. J., Strijder, C., Sze, S. K., Choo, A., Piek, J. J., & Doevendans, P. A. (2011). Human mesenchymal stem cell-conditioned medium improves cardiac function following myocardial infarction. Stem Cell Research, 6(3), 206-214.
8. Arslan, F., Lai, R. C., Smeets, M. B., Akeroyd, L., Choo, A., Aguor, E. N. E., Timmers, L., van Rijen, H. V. M., Doevendans, P. A., Pasterkamp, G., Lim, S. K., & de Kleijn, D. P. V. (2013). Mesenchymal stem cell-derived exosomes increase ATP levels, decrease oxidative stress and activate PI3K/Akt pathway to enhance myocardial viability and prevent adverse remodeling after myocardial ischemia/reperfusion injury. Stem Cell Research, 10(3), 301-312.
9. Timmers, L., Lim, S. K., Hoefer, I. E., Arslan, F., Lai, R. C., van Oorschot, A. A., Goumans, M. J., Strijder, C., Sze, S. K., Choo, A., Piek, J. J., & Doevendans, P. A. (2011). Human mesenchymal stem cell-conditioned medium improves cardiac function following myocardial infarction. Stem Cell Research, 6(3), 206-214.
10. Lai, R. C., Arslan, F., Lee, M. M., Sze, N. S., Choo, A., Chen, T. S., Salto-Tellez, M., Timmers, L., Lee, C. N., El Oakley, R. M., Pasterkamp, G., de Kleijn, D. P., & Lim, S. K. (2010). Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury. Stem Cell Research, 4(3), 214-222.
11. Barile, L., Lionetti, V., Cervio, E., Matteucci, M., Gherghiceanu, M., Popescu, L. M., Torre, T., Siclari, F., Moccetti, T., & Vassalli, G. (2014). Extracellular vesicles from human cardiac progenitor cells inhibit cardiomyocyte apoptosis and improve cardiac function after myocardial infarction. Cardiovascular Research, 103(4), 530-541.
12. Ibrahim, A. G., Cheng, K., & Marbán, E. (2014). Exosomes as critical agents of cardiac regeneration triggered by cell therapy. Stem Cell Reports, 2(5), 606-619.
13. Vrijsen, K. R., Maring, J. A., Chamuleau, S. A., Verhage, V., Mol, E. A., Deddens, J. C., Metz, C. H., Lodder, K., van Eeuwijk, E. C., van Dommelen, S. M., Doevendans, P. A., & Smits, A. M. (2016). Exosomes from cardiomyocyte progenitor cells and mesenchymal stem cells stimulate angiogenesis via EMMPRIN. Advanced Healthcare Materials, 5(19), 2555-2565.
14. Mathieu, M., Martin-Jaular, L., Lavieu, G., & Théry, C. (2019). Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to-cell communication. Nature Cell Biology, 21(1), 9-17.
15. Vrijsen, K. R., Sluijter, J. P., Schuchardt, M. W., van Balkom, B. W., Noort, W. A., Chamuleau, S. A., Doevendans, P. A., & Goumans, M. J. (2010). Cardiomyocyte progenitor cell-derived exosomes stimulate migration of endothelial cells. Journal of Cellular and Molecular Medicine, 14(5), 1064-1070.
16. Mackie, A. R., Klyachko, E., Thorne, T., Schultz, K. M., Millay, M., Ito, A., Kamide, C. E., Liu, T., Gupta, R., Sahoo, S., Misener, S., Kishore, R., Losordo, D. W., & Goukassian, D. A. (2012). Sonic hedgehog-modified human CD34+ cells preserve cardiac function after acute myocardial infarction. Circulation Research, 111(3), 312-321.
17. Vrijsen, K. R., Maring, J. A., Vader, P., van Balkom, B. W., Nawaz, M., Zimmermann, W. H., & Gremmels, H. (2019). Exosomes from cardiomyocyte progenitor cells and mesenchymal stem cells stimulate angiogenesis via EMMPRIN. Advanced Healthcare Materials, 8(13), e1801651.
18. Yi-Sun Song; Bone marrow mesenchymal stem cell-derived vascular endothelial growth factor attenuates cardiac apoptosis via regulation of cardiac miRNA-23a and miRNA-92a in a rat model of myocardial infarction; PLoS One. 2017 Jun 29;12(6):e0179972.
19. Massimiliano Gnecchi; Evidence supporting paracrine hypothesis for Akt-modified mesenchymal stem cell-mediated cardiac protection and functional improvement; FASEB J. 2006 Apr;20(6):661-9.