Myocardial infarction

Myocardial infarction is a leading cause of death and disability in developed countries. After the acute period (first 4 weeks), a scar forms — connective tissue replacing dead myocardium. This scar does not contract, leading to reduction of ejection fraction and chronic heart failure in some patients. Standard therapy — reperfusion (stenting, bypass), antiplatelets, beta-blockers, ACE inhibitors — saves lives and prevents reinfarction, but does not restore dead myocardium. Cell therapy is considered a means of limiting scar size and stimulating regeneration. It is particularly promising in the subacute period (1–3 months post-MI), when the damaged region has not yet been completely replaced by connective tissue.

According to WHO, cardiovascular disease accounts for approximately 32% of all global deaths, of which about 7.7 million annually are due to ischaemic heart disease. In Russia about 520,000 cases of acute coronary syndrome are recorded annually, roughly half being myocardial infarction. The current classification distinguishes STEMI (ST-elevation — typically complete coronary occlusion), NSTEMI (without ST elevation — partial occlusion), and five types under the Universal Definition of Myocardial Infarction: type 1 — atherothrombotic, type 2 — supply/demand mismatch (anaemia, severe hypertension), type 3 — sudden death with ischaemic symptoms, types 4 and 5 — PCI- and CABG-related. Men sustain their first infarction on average 7–10 years earlier than women, but the gap narrows after menopause. Modifiable risk factors include arterial hypertension, dyslipidaemia, smoking, diabetes mellitus, obesity, low physical activity, and adverse psychosocial environment.

Pathophysiologically, myocardial infarction is the endpoint of a long atherosclerotic process. Rupture or erosion of an unstable plaque in a coronary artery exposes thrombogenic substrate — collagen and tissue factor; a thrombus forms and blood flow halts. Within the first 30 minutes irreversible cardiomyocyte death begins; by 6–12 hours necrosis is typically complete unless reperfusion is restored. Reperfusion brings additional injury — oxidative burst, calcium overload, opening of mitochondrial permeability transition pores. Over 2–7 days granulation tissue develops in the lesion, and over 2–4 weeks a fibrotic scar forms. In parallel, adverse left ventricular remodelling unfolds: chamber dilatation, eccentric hypertrophy of surviving segments, interstitial fibrosis. Around the scar a so-called "border zone" persists — chronically hypoperfused hibernating myocardium where cells remain alive but underfunctional. This zone is the principal target of regenerative strategies.

Standard MI care in 2024 is multistep. In the acute period, dual antiplatelet therapy (ASA + a P2Y12 inhibitor — clopidogrel, ticagrelor, or prasugrel), heparin or fondaparinux, high-dose statin, and beta-blocker remain first-line. Reperfusion — primary PCI with door-to-balloon ≤90 minutes, or systemic thrombolysis where PCI is unavailable. In the subacute and chronic periods — 12 months of dual antiplatelet therapy, ACE inhibitor or ARB (or ARNI — sacubitril/valsartan) for reduced ejection fraction, mineralocorticoid receptor antagonist (eplerenone, spironolactone), and SGLT2 inhibitor (dapagliflozin, empagliflozin) — the four pillars of contemporary HFrEF therapy. Cardiac rehabilitation improves survival by 20–25% and is recommended for the majority of patients. In patients with persistent EF <35% beyond 40 days post-MI, an implantable cardioverter-defibrillator (ICD) is indicated; with wide QRS and LBBB — cardiac resynchronisation therapy (CRT-D). Despite this powerful armamentarium, 5-year mortality in post-MI HFrEF remains 40–50%, and none of the standard methods restores dead myocardium.

Cell therapy with mesenchymal cells is conceived as a regenerative bridge between the structural insult and pharmacological control. After IV administration, UC-MSCs and placenta-derived MSCs migrate to perilesional zones with elevated chemokine expression and over several weeks function as a source of pro-angiogenic and anti-inflammatory factors: VEGF, FGF-2, IGF-1 stimulate new capillary formation; HGF and SDF-1 support hibernating cardiomyocyte survival; local MMP-9 falls, attenuating extracellular matrix degradation and adverse remodelling; macrophages switch from M1 to a regenerative M2 phenotype. Direct intercellular mitochondrial transfer through tunnelling nanotubes is also possible into cardiomyocytes with energy metabolism dysfunction. A meta-analysis of 13 RCTs with 956 patients (Stem Cell Research & Therapy, 2021) showed a significant LVEF increase after MSC transplantation — weighted mean +3.78% (95% CI 2.14–5.42; p<0.001). The UC-MSC subgroup analysis in MI and heart failure (2023) confirms reproducibility of effect. A systematic review of mid- to long-term outcomes (Stem Cell Research & Therapy, 2024) indicates that ejection fraction improvement is sustained at 6, 12, 24, and even 36 months.

The Hanshi United programme for myocardial infarction is built around these data. Optimal initiation is 1–3 months post-event, when angioplasty or CABG has stabilised flow, the patient is on full four-pillar HFrEF therapy, and haemodynamics are stable. The standard course consists of three intravenous procedures of UC-MSC or placenta-derived MSCs at 15–20 day intervals. In selected patients with a large border zone on cardiac MRI and ischaemic cardiomyopathy with EF 25–40%, local intracoronary administration is possible in a specialised catheterisation laboratory — this route is considered individually. Dual antiplatelet therapy and all standard HFrEF medications continue without interruption. Efficacy is assessed at 3 and 6 months by echocardiography (EF, GLS, end-systolic volume), the 6-minute walk test, NYHA class, and NT-proBNP. Cell therapy is not an alternative to ICD or CRT and does not eliminate indications for bypass surgery — it is a regenerative complement to a proven standard programme.