Fabrication of polymeric micro-carriers to use in cell therapy in heart.

Fabrication of polymeric micro-carriers to use in cell therapy in heart.
Mahshid Hosseini,^1,* Shohreh Mashayekhan,² Mehdi Khanmohammadi,³
1. Sharif University of Technology
2. Sharif University of Technology
3. Skull Base Research Center, The Five Senses Institute, Hazrat Rasoul Akram Hospital, Iran University of Medical Sciences (IUMS), Tehran, Iran
Introduction: The rate of death among the people suffering from myocardial infarctions is six times more than other persons at the same ages. Because of the inability of conventional methods to regenerate the infarcted part of the heart, cell-based regenerative medicine emerges as a reliable approach. The goal of cell therapy is to form new and functional myocardial tissue by supplying various sources of stem cells. However, due to the low rate of residence and cell viability of the transferred stem cells and their low ability to transplant host tissue into the damaged myocardium, cell therapy has not been clinically efficient and need to develop it. Cellular carriers can be a suitable solution to enhance the survival of transported cells to the myocardium site. Among various methods to generate cell carriers, microfluidic devices are promising systems to fabricate micro-carriers with the minimum adverse effects on cells during the generation of micro-carriers and low invasiveness for their transplantation. The significant point to be mentioned is that those micro-carriers should preserve cells for a long time in order to be effective to regenerate the infarcted tissue.
Methods: A microfluidic device was used to generate micro-carriers with a co-flow microfluidic-based device. Alginate conjugated with phenol moieties (Alg-Ph) was synthesized and utilized as the main polymer because of its biocompatibility. The Alg-Ph was synthesized by combining alginate and tyramine hydrochloride in the existence of N-hydroxysulfosuccinimide(NHS) and N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide in amino reduction reaction. This modified polymer was polymerized by horseradish peroxidase (HRP) and hydrogen peroxide as an electron donor in designed coaxial microfluidic devices, whereas Alg-Ph, HRP, and A549 cell extruded from the inner channel and liquid paraffin saturated with H2O2 from the outer channel.
Results: The degree of Ph conjugation obtained at 1.7×10 -4 mole Ph/g Alg-Ph. We could fabricate spherical micro-carriers containing A549 cells, as a model cell, with radiuses of 70 ± 10 µm and high stability resulting from enzymatic reactions. Following micro-carriers in vitro indicated that they did not degrade after even 30 days, which not only proved their high stability but also made them suitable for delivering cells into the heart tissue. Moreover, trypan blue analysis confirmed that cells were alive within micro-carrier after 30 days, which meant that they could receive adequate oxygen and nutrition to be live.
Conclusion: Fabricated spherical micro-carriers can be a promising approach to solve the low survival of transported cells. As a result, this method can be proposed to improve the efficiency of cell therapy to regenerate infarcted heart tissue.
Keywords: Myocardial infarction, micro-carriers, microfluidic systems, Horseradish Peroxidase crosslinking