Stem Cell Therapy For Myocardial Infarction Research Articles

Stem cell therapy of myocardial infarction: a promising opportunity in bioengineering.

Myocardial infarction (MI) is a life-threatening disease resulting from irreversible death of cardiomyocytes (CMs) and weakening of the heart blood-pumping function. Stem cell-based therapies have been studied for MI treatment over the last two decades with promising outcome. In this review, we critically summarize the past work in this field to elucidate the advantages and disadvantages of treating MI using pluripotent stem cells (PSCs) including both embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), adult stem cells, and cardiac progenitor cells. The main advantage of the latter is their cytokine production capability to modulate immune responses and control the progression of healing. However, human adult stem cells have very limited (if not 'no') capacity to differentiate into functional CMs in vitro or in vivo. In contrast, PSCs can be differentiated into functional CMs although the protocols for the cardiac differentiation of PSCs are mainly for adherent cells under 2D culture. Derivation of PSC-CMs in 3D, allowing for large-scale production of CMs via modulation of the Wnt/β-catenin signal pathway with defined chemicals and medium, may be desired for clinical translation. Furthermore, the technology of purification and maturation of the PSC-CMs may need further improvements to eliminate teratoma formation after in vivo implantation of the PSC-CMs for treating MI. In addition, in vitro derived PSC-CMs may have mechanical and electrical mismatch with the patient's cardiac tissue, which causes arrhythmia. This supports the use of PSC-derived cells committed to cardiac lineage without beating for implantation to treat MI. In this case, the PSC derived cells may utilize the mechanical, electrical, and chemical cues in the heart to further differentiate into mature/functional CMs in situ. Another major challenge facing stem cell therapy of MI is the low retention/survival of stem cells or their derivatives (e.g., PSC-CMs) in the heart for MI treatment after injection in vivo. This may be resolved by using biomaterials to engineer stem cells for reduced immunogenicity, immobilization of the cells in the heart, and increased integration with the host cardiac tissue. Biomaterials have also been applied in the derivation of CMs in vitro to increase the efficiency and maturation of differentiation. Collectively, a lot has been learned from the past failure of simply injecting intact stem cells or their derivatives in vivo for treating MI, and bioengineering stem cells with biomaterials is expected to be a valuable strategy for advancing stem cell therapy towards its widespread application for treating MI in the clinic.

Isosorbide dinitrate improves the efficacy of bone mesenchymal stem cell transplantation via endothelial nitric oxide synthase-dependent mechanism

This study investigated the effect of treatment wientry isosorbide dinitrate (Isoket) on bone mesenchymal stem cell (BMSC) transplantation in a rat model of myocardial infarction (MI) and its possible mechanism. Sprague-Dawley (SD) rats were randomized to a sham operation group, MI control group, BMSC transplantation group, and Isoket-BMSCs transplantation group. Isosorbide dinitrate (Isoket, 5 μg/m) was administered by intraperitoneal injection (10 ml/kg) at 0, 12, and 24 hours following ischemia/reperfusion induction of MI models. Left ventricular function, myocardial infarct size (MIS), the survival of engrafted BMSCs, and expression of vascular endothelial growentry factor (VEGF), inducible nitric oxide synthase (iNOS), and endothelial nitric oxide synthase (eNOS) proteins were detected 2 weeks post-transplantation. The results showed isosorbide dinitrate attenuated cardiac dysfunction, increased the survival of engrafted cells in the ischemic heart and promoted iNOS, eNOS, and VEGF protein expression. It is suggested that isosorbide dinitrate enhances mesenchymal stem cell therapy for MI via an eNOS-dependent mechanism.

Challenges for heart disease stem cell therapy

Cardiovascular diseases (CVDs) are the leading cause of death worldwide. The use of stem cells to improve recovery of the injured heart after myocardial infarction (MI) is an important emerging therapeutic strategy. However, recent reviews of clinical trials of stem cell therapy for MI and ischemic heart disease recovery report that less than half of the trials found only small improvements in cardiac function. In clinical trials, bone marrow, peripheral blood, or umbilical cord blood cells were used as the source of stem cells delivered by intracoronary infusion. Some trials administered only a stem cell mobilizing agent that recruits endogenous sources of stem cells. Important challenges to improve the effectiveness of stem cell therapy for CVD include: (1) improved identification, recruitment, and expansion of autologous stem cells; (2) identification of mobilizing and homing agents that increase recruitment; and (3) development of strategies to improve stem cell survival and engraftment of both endogenous and exogenous sources of stem cells. This review is an overview of stem cell therapy for CVD and discusses the challenges these three areas present for maximum optimization of the efficacy of stem cell therapy for heart disease, and new strategies in progress.

Establishment of a rat model of myocardial infarction with a high survival rate: A suitable model for evaluation of efficacy of stem cell therapy

The most common rat model of myocardial infarction (MI) is by ligation of left anterior descending (LAD) coronary artery but it is associated with high mortality and large variations in the infarct size. We evolved certain innovations/modifications in the existing technique including immobilization of the heart without exteriorization, identification of the LAD by pressing it proximal to the site of ligation by an ear-bud, and subsequently its ligation 8 mm from its origin, no touch technique of the lungs during surgery, removal of air from the chest cavity prior to its closure using an in-house tubing, and deflation of the lungs before extubation. We induced MI in 24 Sprague- Dawley (SD) rats using these modifications and carried out post-MI evaluation of hemodynamic parameters, serum cardiac enzymes and histological studies upto 90 days using 13 sham operated and 3 healthy SD rats as controls. Three of the 24 rats (13%) died <24 hours of MI, but thereafter no mortality was observed till the follow-up period of 90 days. The infarct size was consistent in all the rats (21±4% of left ventricular area). This model with low early and no long-term mortality may be suitable for studying efficacy of stem cell therapy in MI, where a follow-up of at least 13 weeks is required to assess myocardial regeneration.