A nondenatured, noncrosslinked collagen matrix to deliver stem cells to the heart

Abstract

Aims: Stem cell transplantation holds promise as a therapeutic approach for the repair of damaged myocardial tissue. One challenge of this approach is efficient delivery and long-term retention of the stem cells. Although several synthetic and natural biomaterials have been developed for this purpose, the ideal formulation has yet to be identified. Materials & methods: Here we investigate the utility of a nondenatured, noncrosslinked, commercially available natural biomaterial (TissueMend® [TEI Biosciences, Boston, MA, USA]) for delivery of human mesenchymal stem cells (MSCs) to the murine heart. Results: We found that MSCs attached, proliferated and migrated within and out of the TissueMend matrix in vitro. Human MSCs delivered to damaged murine myocardium via the matrix (2.3 × 104 ± 0.8 × 104 CD73+ cells/matrix) were maintained in vivo for 3 weeks and underwent at least three population doublings during that period (21.9 × 104 ± 14.4 × 104 CD73+ cells/matrix). In addition, collagen within the TissueMend matrix could be remodeled by MSCs in vivo, resulting in a significant decrease in the coefficient of alignment of fibers (0.12 ± 0.12) compared with the matrix alone (0.28 ± 0.07), and the MSCs were capable of migrating out of the matrix and into the host tissue. Conclusion: Thus, TissueMend matrix offers a commercially available, biocompatible and malleable vehicle for the delivery and retention of stem cells to the heart.