-
[show abstract]
[hide abstract]
ABSTRACT: Previous regenerative studies have demonstrated massive cell losses after intramyocardial cellular delivery. Therefore, efforts at reducing mechanical losses may prove more successful in optimising cellular therapy. In this study, we hypothesized that escalating mesenchymal stem cells (MSCs) dose will not produce corresponding improvement in cardiac function due to washout of the small cells in microcirculation. Using microspheres similar in size to MSCs, that are encapsulated in alginate-poly-l-lysine-alginate (APA), we tested the hypothesis that size is an important factor in early losses.
In experiment I, five groups of rats (n=9 each) underwent coronary ligation; group I had no treatment; the other groups received escalating 0.5 × 10(6), 1.5 × 10(6), 3 × 10(6) and 5 × 10(6) of MSCs each. Echocardiogram was performed at baseline, 2 days and 7 weeks after surgery. In experiment II, cell-sized microspheres (10 μm) were encapsulated in APA microcapsules. In group I (n=16), rats received bare microspheres, group II (n=16) microspheres within 200 μm microcapsules and in group III (n=16), microspheres within 400 μm microcapsules. After 20 min, hearts were quantified for the amount retained.
Myocardial function did not improve further with escalating cell doses beyond an initial response at 1.5 × 10(6) cells. Encapsulated microspheres in 200 μm and 400 μm microcapsules demonstrated a fourfold increase in retention rate compared with 10 μm microspheres.
We concluded that suboptimal functional improvement in this animal model starts at 1.5 × 10(6) cells and does not respond to escalating cell doses. Improving mechanical retention is possible by increasing the size of the injectate. Microencapsulation could be used to encapsulate donor cells and facilitate functional improvement in cellular heart failure therapy.
European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery 02/2011; 39(2):241-7. · 2.40 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The mechanism by which marrow stromal cells (MSCs) improve cardiac function after myocardial infarction (MI) is still unclear. Because MI patients with lower circulating proinflammatory/antiinflammatory cytokine ratios have been reported to have a better prognosis and in vitro studies showed that MSCs express antiinflammatory cytokines, we hypothesized that changes in cytokine ratios in the infarct microenvironment after MSC therapy may play a role in improving early cardiac function after MI.
Sixty-three rats that survived left coronary artery ligations were injected with culture media (group M) or MSCs (group C). Cardiac functional changes were assessed with echocardiography. Cytokine gene expressions of interleukin (IL)-1beta, IL-6, IL-8, (proinflammatory) and IL-10 (antiinflammatory) were quantified by real-time polymerase chain reaction. Extracellular matrix deposition, injury score, and the matrix metallopeptidase 2/tissue inhibitor of metallopeptidase 1 ratio were also analyzed.
The ratio of proinflammatory/antiinflammatory cytokine gene expression was decreased in group C at various times, particularly in the early postoperative period. In group C, the matrix metallopeptidase 2/tissue inhibitor of metallopeptidase 1 gene expression ratio was significantly lower than group M at the early phase (12 hours), which in group C was translated into significantly lower extracellular matrix deposition at 24 hours, 1, and 2 weeks. Functional recovery was also significantly better in cell therapy group C.
Our data demonstrate that MSC therapy decreases the proinflammatory/antiinflammatory cytokine ratio in the microenvironment early after MI. This is associated with subsequent less scar formation and improved cardiac function.
The Annals of thoracic surgery 07/2010; 90(1):190-7. · 3.74 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Stem cells have the unique properties of self-renewal, pluripotency and a high proliferative capability, which contributes to a large biomass potential. Hence, these cells act as a useful source for acquiring renewable adult cell lines. This, in turn, acts as a potent therapeutic tool to treat various diseases related to the heart, liver and kidney, as well as neurodegenerative diseases such as Parkinson's and Alzheimer's disease. However, a major problem that must be overcome before it can be effectively implemented into the clinical setting is a suitable delivery system that can retain an optimal quantity of the cells at the targeted site for a maximal clinical benefit; a system that will give a mechanical as well as an immune protection to the foreign cells, while at the same time enhancing the yields of differentiated cells, maintaining cell microenvironments and sustaining the differentiated cell functions. To address this issue we opted for a novel delivery system, termed the 'artificial cells', which are semipermeable microcapsules with strong and thin multilayer membrane components with specific mass transport properties. Here, we briefly introduce the concept of artificial cells for encapsulation of stem cells and investigate the application of microencapsulation technology as an ideal tool for all stem transplantations and relate their role to the emerging field of cellular cardiomyoplasty.
Regenerative Medicine 09/2009; 4(5):733-45. · 3.72 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Transvenous coronary sinus lead placement is currently the standard approach for left ventricular pacing. The aim of this study is to assess whether a mini-thoracotomy approach would be feasible and safe when used for cases in which transvenous procedures were ineffective or judged unlikely to succeed. Biventricular pacing was performed in 138 consecutive patients with 47 patients undergoing a mini-thoracotomy procedure. NYHA status, quality of life, electrical and echocardiographic data were assessed in the two groups over a follow-up period of 17.6+/-4.2 weeks. There was no significant difference in the preoperative characteristics in both groups other than a greater prevalence of renal failure and previous cardiac surgery among the surgical patients. The mean procedure time was significantly longer in the transvenous group. No significant differences were noted in the immediate or long-term pacing parameters. Two mortalities were observed in the surgical group >2 weeks following the procedure. During the follow-up period, we noted a comparable improvement in the echocardiographic parameters, QRS duration and NYHA status with both approaches. Our results suggest that even when performed on high-risk patients, epicardial lead placement through a mini-thoracotomy is beneficial and feasible as a 'rescue' procedure after a failed transvenous approach.
Interactive cardiovascular and thoracic surgery 07/2008; 7(5):839-44.
-
[show abstract]
[hide abstract]
ABSTRACT: Experimental and clinical studies have proven the feasibility of cellular cardiomyoplasty in treating the damaged myocardium following ischemic injury. Over the years, this field has exploded with different investigators trying different routes of cell delivery ranging from direct cell injection into the heart to peripheral intravenous delivery utilizing the various signaling mechanisms known. These different routes have resulted in a wide range of retention and engraftment of cells in the target tissues. In this review, we will explore the different modalities of cell delivery, the pros and cons of each route and the cellular retention and therapeutic efficacy of these routes. We will then look into the different theories that try to explain the observed retention and engraftment of cells in the target tissues. Finally, we will discuss various methods that can improve cellular retention and engraftment and hence better improvement in myocardial function.
Frontiers in Bioscience 02/2008; 13:2421-34. · 3.52 Impact Factor
