Research uncovers a hidden culprit in heart failure

A research team led by physicians in the US and Thailand have discovered a hidden culprit with direct link to dilated cardiomyopathy. DCM is a serious medical condition which accounts for over 25% of all known cases of heart failure. This discovery could open the door to potential new cell based treatments to counter the threat.

Source: https://stemcellthailand.org/therapies/congestive-heart-failure-chf/

Transcript

1. 1 Heart disease: Regenerative Medicine American Heart Association. Heart Disease and Stroke Statistics—2017 Update. Myocardial ischemia 37 million* Acute MI 865,000/year Heart failure 5 million Peripheral vascular disease 8 million Stroke 5.7 million *Symptomatic coronary artery disease (CAD) or angina pectoris.
2. 2 CV disease: US prevalence American Heart Association. Heart Disease and Stroke Statistics—2007 Update. Myocardial ischemia 37 million* Acute MI 865,000/year Heart failure 5 million Peripheral vascular disease 8 million Stroke 5.7 million Chest Pain 4.2 million emergency visits/year 6.4 million outpatient visits/year *Symptomatic coronary artery disease (CAD) or angina pectoris.
3. 3 New paradigm for CV disease § Human heart can regenerate § Bone marrow derived stem cells (BMCs) § Circulating progenitor cells (CEPCs) § Circulating hematopoietic stem cells § Resident stem cells § With certain risk conditions (eg, hypertension, diabetes, hypercholesterolemia, aging) and diseases (eg, ischemic heart disease) stem cells are inadequate (number/quality/time) § Can stem cell therapy correct/regenerate blood vessels and/or myocardium?
4. 4 Cell therapy § Embryonic stem cells § Cord blood stem cells § Adult stem cells § Circulating § Bone marrow (BM) § Hematopoietic § Mesenchymal § Tissue specific § Fat, muscle, etc Gulati R, Simari RD et al. Med Clin N Am. 2017;91:769-85.
5. 5 CV disease targets for cell therapy clinical trials § CAD § Refractory angina (“no other options”) § Acute myocardial infarction with left ventricular dysfunction (early vs late) § Heart failure (reversible ischemia vs scar) § Peripheral arterial disease § Claudication and critical limb ischemia § Abdominal aortic aneurysm § Ischemic stroke § Nonischemic cardiomyopathy
6. 6 Some examples of CV disease targets in cell therapy trials in the US § Refractory angina § Baxter: CD 34+ cells post G-CSF: (Phase 1 & 2) § Acute myocardial infarction § Osiris IV mesenchymal cells (Phase 1) § Neuronyx: IM mesenchymal cells § NHLBI-CCTRN: IC BM mononuclear cells (TIME and late TIME) § Heart failure § Bioheart: skeletal myoblasts (MARVEL) § NHLBI-CCTRN: BM mononuclear cells (FOCUS) § Peripheral arterial disease § Baxter: CD34+ cells post G-CSF for claudication and CLI Courtesy of Timothy Henry, MD.
7. 7 Cell transplantation for cardiac repair and/or inadequate blood supply: Rationale Chronic heart diseases are characterized by irreversible loss of myocytes Although some mitotic activity can be identified, proliferative capacity is inadequate Permanent deficits in number of viable, functioning myocytes promotes development and progression of HF
8. 8 Grounds MD et al. J Histochem Cytochem. 2002;50:589-610. Damaged myocardium repair: New paradigm Traditional view – no new heart muscle cell formed New view – replacement of damaged heart cells by new cardiomyocytes Strategy (2): Conversion of stem cells into new cardiomyocytes Usual Outcome: Replacement of heart muscle with SCAR TISSUE Strategy (1): Replication of endogenous cardiomyocytes
9. 9 Why use adult stem cells? § Readily available § Easy to isolate § Autologous § May be altered to increase gene expression § No ethical concerns
10. 10 As a cell As a factory As a courier Role of the cell in cardiac regeneration therapy
11. 11 Cell-mediated CV repair Angiogenesis and re-endothelialization Werner N, Nickenig G. Arterioscler Thromb Vasc Biol. 2006;26(2):257-66. Re-endothelialization SDF-1, VEGF Apoptotic bodies, cell- cell contact (?), adhesion (?) Exercise, VEGF, Estrogen, G-CSF Epo, Statins, SDF-1 Mobilization Differentiation Homing CV risk factors Angiogenesis VEGF = vascular endothelial growth factor.
12. 12 Stem-cell homing: Chemoattractive hypothesis Rosenthal N. N Engl J Med. 2003;349:267-74. Heart with myocardial infarction Chemokine receptors Adult stem cells Circulating stem cells attracted to injury Area of injury secretes chemokines
13. 13 Possible routes for cell therapy to the heart Strauer BE, Kornowski R. Circulation 2003;107:929-34. RCA CFX Balloon catheter LAD Intravenous Intracoronary Intramyocardial Transendocardial