Time-Dependent Effects on Coronary Remodeling and Epicardial Conductance after Intracoronary Injection of Enriched Hematopoietic Bone Marrow Stem Cells in Patients with Previous Myocardial Infarction

Abstract

Bone marrow (BM) cells may interact with coronary endothelium and modulate coronary atherosclerosis. We investigated the time course of coronary luminal loss and changes in conductance after intracoronary injection of enriched hematopoietic BM stem cells in patients with previous myocardial infarction (MI). Among 24 patients with acute MI, 13 were randomized to early (<7 days) and 11 to late (4 months) intracoronary injection of CD133 + cells after the infarction. Segmental quantitative coronary angiography and fractional flow reserve (FFR) measurements of the infarct-related (IR) artery (A) and contralateral artery (control) were performed. In the early group, at 4 months, cumulative luminal loss (LL) of the minimal luminal diameter (MLD) of the IRA distal to the stented segment was −0.39 (−0.51-0.10) mm (p < 0.05 vs. control). There was no further change in LL between 4 and 8 months [−0.09 (−0.26-0.15 INTRODUCTIONinfused early after myocardial infarction, exerted beneficial effects on cardiac recovery in patients with reperfused myocardial infarction, but they appeared to be asCell-induced angiogenesis is mainly mediated by paracrine effects through the release of cytokines, adhesion sociated with higher luminal loss of downstream distal segments at 4 months follow-up. Therefore, we investimolecules, and growth factors. However, similar cytokines and molecules participate in pathogenesis of athgated long-term effects of intracoronary CD133 + -enriched cells on luminal loss of distal nonstented segments of erosclerosis, and striking similarities in the molecular mechanisms underlying both processes are well docuthe infarct-related artery in a separate group of patients with recent myocardial infarction treated with stented mented (6). Furthermore, opposing effects on angiogenesis and atherogenesis were observed in studies using angioplasty randomized to early and late stem cell treatment. cytokines or growth factors involved in both processes (5,8,9,13,17,21). This led to the hypothesis that interre- MATERIALS AND METHODS lated tradeoffs may be inherent to therapies designed toPatients and Study Protocol enhance collateral formation (6). The concept coined as "Janus-like" phenomenon (6) may have important cliniThe study population consisted of 24 patients with acute myocardial infarction (MI) due to occlusion of the cal implications for intracoronary stem cell therapy. In our previous studies (1,14), CD133 angioplasty. All patients underwent cardiac catheterizaCardiac Catheterization tion between 5 and 7 days after the infarction (baseline), LV volumes and ejection fraction were calculated usand at 4 and 8 months follow-up. Patients were randoming the area-length method. Regional wall motion was ized into two groups. The first group received intracoroanalyzed using the centerline method. nary cell therapy at baseline (early group) within 7 days Assessment of Luminal Loss by Quantitative following the MI and the second group received cells at Coronary Angiography 4 months (late group). In all patients and at al...

Mesenchymal stem cells over-expressing SDF-1 promote angiogenesis and improve heart function in experimental myocardial infarction in rats☆

“…Several studies showed that cell transplantation at 1-2 weeks post-infarction exerted better effects on increases in the survival of engrafted cells, angiogenesis and functional cardiomyocytes in the injured hearts than immediately, 24 h or at 4 weeks following the infarction. At these time-windows, scar formation has not occurred and the inflammation is reduced, which should facilitate the integration of transplanted cells and functional recovery [23]. The controversy may be related to differences in cell origin, cell preparation and detection methodology.…”

Transplantation of Endothelial Progenitor Cells as Therapeutics for Cardiovascular Diseases

“…The infusion or injection of stem or progenitor cells has been shown to improve neovasCell therapy is currently attracting growing attention as a potential issue of improving the prognosis of pacularization and heart function after ischemia in various experimental studies and clinical trials (46,52,106). tients with cardiovascular diseases (22,52,77,97,113). Cell-based therapy to stimulate postnatal vasculogenesis EPCs can migrate to the site of blood vessel injury to help repair the damage and to differentiate into mature or to repair the integrity is being evaluated for cardiovascular diseases with excess morbidity and mortality, endothelial cells (37).…”

Glucose-6-phosphate dehydrogenase plays a critical role in hypoxia-induced CD133+progenitor cells self-renewal and stimulates their accumulation in the lungs of pulmonary hypertensive rats

“…ϩ and bone marrow-derived stem cells also contribute to tumorigenesis (39,47,54) and pathogenic remodeling that reduces conductance in coronary (49) and pulmonary arteries (13,28,48,51), thereby contributing to chronic hypoxiainduced pulmonary hypertension (23,41). In response to hypoxia, circulating bone marrow-derived CD34 ϩ /CD133 ϩ /Flk ϩ and c-kit ϩ cells are recruited to the adventitial, medial or intimal compartments, where they assume mesenchymal or smooth muscle cell-like characteristics (29,38,43).…”