Prevention of Cardiovascular Disease

About

Preventive medicine is a proactive approach focused on maintaining health and preventing the occurrence or progression of disease (1).

Cardiovascular disease

Cardiovascular disease (CVD) is a group of disorders of the heart and blood vessels, such as coronary artery disease, myocardial infarction (heart attack), heart failure, arrhythmias, and stroke. CVD is the leading cause of death globally, accounting for an estimated 20 million deaths each year, as reported by the World Heart Federation (2). The onset of CVD may seem binary for the individual patient, one day patients are healthy and the next they have suffered a CVD event such as a heart attack or a stroke. CVDs are mostly age-related chronic diseases with an earlier onset than an eventual cardiovascular event. The vascular pathophysiology leading up to the first CVD event has often been gradually developing asymptomatically over the years, driven by, among other things, chronic tissue inflammation, endothelial dysfunction, atherosclerosis and increased blood pressure, before the individual becomes aware of it (3). A vast majority of treatments are interventions after a cardiovascular event has occurred, and consequently, preventative efforts are mostly secondary, and therapies often reduced to monitoring symptoms. Prevention of cardiovascular disease stands out as a paramount and urgent priority in the real world.

Why Research on Preventative Medicine is Important

The concept of preventive medicine is on the rise. However, there is a need for more research and scientific evidence on how to promote healthy longevity by slowing down or preventing, among other things, the chronic inflammation that often drives the development of age-related diseases. Despite maintaining a healthy lifestyle, our susceptibility to age-related chronic diseases persists due to the gradual onset of low-grade inflammation and diminished regenerative capacity that naturally occurs in the body as we age (4). The anti-inflammatory, immunomodulatory and regenerative properties of MSCs have made them highly interesting in the field of preventative medicine.

How Mesenchymal Stem Cells Could Help Prevent Disease

MSCs are among the most frequently researched cell types in regenerative medicine. A large number of experimental studies have shown that both local and systemic administration of MSCs suppresses detrimental immune responses in inflamed tissues and promotes tissue repair (5).

MSCs have been shown to migrate to sites of injury and inflammation in response to environmental signals, where they interact with the local microenvironment, primarily by secretion of numerous bioactive molecules and through cell-to-cell contact (6-7). The intricate mechanisms of MSC are believed to include modulating the immune response to attenuate harmful inflammation and promote regeneration, promoting survival and regeneration of injured cells, stimulation of endogenous progenitor cells, induction of new blood vessels in damaged tissue (6-7) and improving endothelial function (8).

Clinical and pre-clinical studies of MSC have shown promising results regarding the potential of prevention of cardiovascular events (9-13). One large-scale clinical study with >500 participants, published in 2023, reported a potential preventative effect of MSC on cardiovascular events, such as heart attack and stroke (9).

According to this study, where MSCs were injected directly into the heart muscle of heart failure patients, there was a significantly reduced risk for myocardial infarction and stroke, over a mean follow-up of 30 months. Most benefit could be seen in patients with evidence of systemic inflammation.

The study also indicated a strengthened heart function, measured as left ventricular ejection fraction (LVEF), for patients receiving the treatment compared to the control group.

The results of this study raised the possibility that MSCs might improve cardiovascular health by targeting local cardiac and systemic inflammatory changes that cause macrovascular and microvascular abnormalities.

Acknowledging the gradual development of CVD, not only secondary prevention but also primary preventative treatment, is an interesting strategy to examine further. Stem cells hold promise for possibly mitigating the risk factors and reducing the incidence of these major health conditions.

Due to their anti-inflammatory, regenerative, and immunomodulatory properties, MSCs are an especially interesting candidate for preventive treatments, i.e., even for individuals without clinical symptoms, since ageing-related diseases and vascular degeneration are in part driven by inflammation accelerated or slowed down by individual lifestyle, comorbidities, inherited genetics, age, and many other factors.

Global research on MSCs for other age-related chronic conditions include:

Diabetes (14)
Ageing frailty (15)
Neurodegenerative Diseases, such as Alzheimer’s (16-17)
Respiratory Diseases (18)
Orthopaedic Diseases – please see our Musculoskeletal injuries and Osteoarthritis studies.

In conclusion, even though the complex mechanisms of action of MSCs in humans have not been fully understood yet, MSCs hold great potential as a novel approach in preventive medicine, given their anti-inflammatory, regenerative and immunomodulatory properties.

Safety Profile:

Mesenchymal Stem Cells (MSCs) sourced from bone marrow have been extensively researched in scientific studies. A meta-analysis published in 2021 reviewed 62 randomised clinical trials and concluded that MSC treatment was safe compared to placebo. No serious adverse events were discovered across the included studies (19).

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2. World Heart Federation, World Heart report 2023 World-Heart-Report-2023.pdf (world-heart-federation.org) 

3. Buja, L. Maximilian, and Jagdish Butany, eds. Cardiovascular pathology. Academic Press, 2022.

4. Ferrucci L, Fabbri E. Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty. Nat Rev Cardiol. 2018 Sep;15(9):505-522. doi: 10.1038/s41569-018-0064-2. PMID: 30065258; PMCID: PMC6146930.

5. Krampera M, Le Blanc K. Mesenchymal stromal cells: Putative microenvironmental modulators become cell therapy. Cell Stem Cell. 2021 Oct 7;28(10):1708-1725. doi: 10.1016/j.stem.2021.09.006. PMID: 34624232.

6. Caplan AI, Correa D. The MSC: an injury drugstore. Cell Stem Cell. 2011 Jul 8;9(1):11-5. doi: 10.1016/j.stem.2011.06.008. PMID: 21726829; PMCID: PMC3144500.

7. Murphy MB, Moncivais K, Caplan AI. Mesenchymal stem cells: environmentally responsive therapeutics for regenerative medicine. Exp Mol Med. 2013 Nov 15;45(11):e54. doi: 10.1038/emm.2013.94. PMID: 24232253; PMCID: PMC3849579.

8. Hare JM, DiFede DL, Heldman AW et al. Randomized Comparison of Allogeneic Versus Autologous Mesenchymal Stem Cells for Nonischemic Dilated Cardiomyopathy: POSEIDON-DCM Trial. J Am Coll Cardiol. 2017 Feb 7;69(5):526-537. doi: 10.1016/j.jacc.2016.11.009. Epub 2016 Nov 14. PMID: 27856208; PMCID: PMC5291766.

9. Perin E, Borow K, Henry T, et al. Randomized Trial of Targeted Transendocardial Mesenchymal Precursor Cell Therapy in Patients With Heart Failure. J Am Coll Cardiol. 2023 Mar, 81 (9) 849–863.https://doi.org/10.1016/j.jacc.2022.11.061

10. Yu-Ling Lin, Shaw-Fang Yet, Yuan-Tong Hsu, Guei-Jane Wang, Shih-Chieh Hung, Mesenchymal Stem Cells Ameliorate Atherosclerotic Lesions via Restoring Endothelial Function, Stem Cells Translational Medicine, Volume 4, Issue 1, January 2015, Pages 44–55, https://doi.org/10.5966/sctm.2014-0091

11. Perin, E.C., Borow, K.M., Silva, G.V., DeMaria, A.N., Marroquin, O.C., Huang, P.P., Traverse, J.H., Krum, H., Skerrett, D., Zheng, Y. and Willerson, J.T., 2015. A phase II dose-escalation study of allogeneic mesenchymal precursor cells in patients with ischemic or nonischemic heart failure. Circulation research, 117(6), pp.576-584.

12. Wang SS, Hu SW, Zhang QH, Xia AX, Jiang ZX, Chen XM. Mesenchymal stem cells stabilize atherosclerotic vulnerable plaque by antiinflammatory properties. PloS One. 2015;10: e0136026.

13. Wang ZX, Wang CQ, Li XY, et al. Mesenchymal stem cells alleviate atherosclerosis by elevating number and function of CD4(þ)CD25 (þ)FOXP3(þ)regulatory T-cells and inhibiting macrophage foam cell formation. Mol Cell Biochem. 2015;400:163–172.

14. Li Y, Wang F, Liang H, et al. Efficacy of mesenchymal stem cell transplantation therapy for type 1 and type 2 diabetes mellitus: a meta-analysis. Stem Cell Res Ther. 2021;12(1):273. Published 2021 May 6. doi:10.1186/s13287-021-02342-5

15. Tompkins BA, DiFede DL, Khan A, et al. Allogeneic Mesenchymal Stem Cells Ameliorate Aging Frailty: A Phase II Randomized, Double-Blind, Placebo-Controlled Clinical Trial. J Gerontol A Biol Sci Med Sci. 2017;72(11):1513-1522. doi:10.1093/gerona/glx137

16. Brody, M. et al. (2022) ‘Results and insights from a phase I clinical trial of lomecel‐b for alzheimer’s disease’, Alzheimer’s & Dementia, 19(1), pp. 261–273. doi:10.1002/alz.12651.

17. Staff, N. P., Jones, D. T., & Singer, W. (2019). Mesenchymal Stromal Cell Therapies for Neurodegenerative Diseases. Mayo Clinic proceedings, 94(5), 892–905. https://doi.org/10.1016/j.mayocp.2019.01.001

18. Cruz, F.F. and Rocco, P.R.M., 2020. The potential of mesenchymal stem cell therapy for chronic lung disease. Expert Review of Respiratory Medicine, 14(1), pp.31-39.

19. Wang Y, Yi H, Song Y. The safety of MSC therapy over the past 15 years: a meta-analysis. Stem Cell Res Ther. 2021;12(1):545. Published 2021 Oct 18. doi:10.1186/s13287-021-02609-x