Microencapsulation to reduce mechanical loss of microspheres: Implications in myocardial cell therapy

Divisions of Cardiac Surgery and Surgical Research, McGill University Health Center, McGill University, Montreal, Quebec, Canada.
European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery (Impact Factor: 3.3). 02/2011; 39(2):241-7. DOI: 10.1016/j.ejcts.2010.03.066
Source: PubMed


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.

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    • "Recently, the importance of scaffold size for intra-myocardial injection has been reported for scaffold/cell complex retention in the beating heart [101]. For instance, augmenting from 10 mm to 400 mm the size of alginate-poly-L-lysine-alginate microspheres encapsulating MSCs, a fourfold increase in cell retention rate was observed [101]. Hydrogels with an in situ gelling process have also been extensively studied these last years due to the possibility of a direct injection in the ischemic area using a catheter/ needle [102] [103]. "
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    • "LVFS for group I reached 16.5% at 8 weeks post-MI. This result is comparable to the authors’ previous study that examined LVFS for a control group that received only culture medium at 7 weeks.7 This comparison proves that the nanoparticles used had no negative effect on the heart. "
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    • "Cardiac cell transplantation is limited mainly due to poor graft viability [2]. Our recent findings on animal studies have demonstrated that microencapsulated cell delivery system can increase the transplanted cell retention capacity by four times in comparison to free cells when injected intramyocardially in a beating heart [16, 54, 55]. To further reduce the biological and mechanical loss of the transplanted cardiomyocytes in the harsh contractile myocardial environment, we modified the alginate microcapsules by incorporating PEG. "
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