Central zone of myocardial infarction: a neglected target area for heart cell therapy

Abstract

The purpose of this study was to investigate the fate of transplanted cells in the central zone of myocardial infarction (MI), and to clarify the relationship between the injection-site impact and the efficacy of cell therapy. MI was created by coronary ligation in female rats. Three weeks later, 3-million labelled male bone marrow mesenchymal stem cells (BMSCs) were directly injected into the border (BZC group) or central zone (CZC group) of MI area. As a control, culture medium was injected into the same sites. Cell survival was evaluated by quantitative real-time polymerase chain reaction, and apoptosis was assayed with TUNEL and caspase-3 staining. Four weeks after transplantation, heart function and cardiac morphometry were evaluated by echocardiography and Masson’s Trichrome staining, respectively. Angiogenesis and myogenesis were detected by immunofluorescence staining. After cell transplantation into the border or central zone, there was no cell migration between the different zones of MI. BMSCs in the CZC group exhibited no difference in apoptotic percentage, in the long-term survival, when compared with those in the BZC group. However, they did effectively promote angiogenesis and cellular myogenic differentiation. Although cell delivery in the central zone of MI had no effect on the recovery of heart function compared with the BZC group, the retained BMSCs could still increase the scar thickness, and subsequently exhibit a trend in the reverse remodelling of ventricular dilation. Hence, we concluded that the central zone of MI should not be ignored during cell-based therapy. Multiple site injection (border+central zone) is strongly recommended during the procedure of cell transplantation.

Experimental acute myocardial infarction: telocytes involvement in neo-angiogenesis

“…It is widely accepted that after 30 days of experimental myocardial infarction, the border zone of the lesion is characterized by neo‐angiogenesis [13, 51]. Generally, there are many types of angiogenic factors: e.g.…”

“…Understanding the mechanisms of cardiac regeneration and repair after myocardial infarction is an important subject of contemporary medicine. The effects of experimental myocardial infarction were frequently reported [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16]. Indeed, according to PubMed database, there are 3840 titles (from 1956 to August 2011) for the 'rat myocardium infarction' search!…”

Cardiac cell therapy: current status and future trends

“…Injections are most frequently made into the left ventricle by a direct epicardial approach or by an indirect transendocardial approach with an intraventricular catheter. The epicardial and transendocardial routes are more invasive than intracoronary or intravenous approaches, but direct injection is more reliable (Jin et al ., 2012). Figure 15.1 depicts bioluminescent imaging after cell injection by each of the three most popular routes (Li et al ., 2009).…”

Intraoperative Stem Cell Therapy

“…In general, intraoperative isolation and application of cells have promoted revascularization, resulting in enhanced myocardial perfusion, and contractility of infarct areas, leading to improvement in left ventricular ejection fraction (59, 65). Although injection of bone marrow–derived MSCs into peri-infarct areas may improve contractility and although injection of cells into the central zone of the myocardial infarction can promote angiogenesis, myogenic differentiation, and reverse ischemic remodeling (68), administration of bone marrow–derived cells directly into nonviable scarred myocardium does not appear to improve contractile function (62, 68). Therefore, when considering the cell delivery strategy for the regeneration of damaged heart tissue, it may be important to consider multiple sites of injection, including viable, peri-infarct areas and the central zone of the myocardial infarction (68).…”