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C H A P T E R 5

Biomaterials as Vehicles for Stem Cell Delivery and Retention in the Infarct

CHAPTER SUMMARY

Poor cell engraftment and survival in the infarct are the major limitations of the strategy is of cell suspension transplantation to treat and regenerate the infarcted myocardium after MI. This chapter describes the application of biomaterials as delivery vehicles to improve cell survival and function after transplantation.The results of this strategy, in terms of cell retention, integration, and beneficial effect on cardiac repair are presented for the different stem and progenitor cells used in cardiac repair. At the end, we present the “MAGNUM” phase 1 clinical trial with implantable cardiac patches based on bone marrow cells seeded in collagen type I that provided an initial proof-of-concept for the potential use of biomaterials to enhance cell integration and cardiac repair.

5.1INTRODUCTION

As already mentioned, a large body of evidence from preclinical and clinical trials indicates some functional improvements in heart function after MI, even with the injections of suspensions of noncontractile cells. These include various populations of stem/progenitor cells (bone marrow, adipose, or cardiac tissue-derived). Aside from the apparent efficacy shown by stem cell transplantation in various animal models, several critical hurdles associated with this strategy arose. First, the retention of cells immediately after delivery is highly dependent on the administration strategy: if cells are injected intramyocardially during open-chest surgery, many cells are lost through the vasculature, and only a few cells infused into the coronary arteries do ultimately engraft. Second, survival in the inflammatory environment of the acute infarcted myocardium is a challenge common to all types of transplanted cells, as typically 90% of the cells die within a week after transplantation. In addition, cell retention is extremely variable from one study to another, making final graft size unpredictable. Finally, virtually all studies involving cell suspension transplantation into the heart have found that the scar tissue forms a major barrier to proper integration of the implanted cells [1, 2].

The use of biomaterials as a platform or vehicle for cell delivery into the infarcted myocardium seems like a very logical strategy, which can potentially reduce or eliminate the obstacles seen in cell suspension transplantation [3]. The biomaterials can protect the implanted cells from the aggressive