Human Bone Marrow Mesenchymal Stem Cells Seeded on Modified Collagen Improved Dermal Regeneration In Vivo

Abstract

In the correction of functional and aesthetic impairments, loss of soft connective tissue creates the need for adequate implant material. The reconstruction of defects resulting from radical excisions, trauma, or hereditary diseases has seen the use of combined grafts and flaps. With the aim of minimizing donor site morbidity, new methods have been evaluated. Because of a low rate of vascularization, with artificial dermal templates the take has only been poor. As shown in previous studies, improved angiogenetic potency and epidermal formation has been obtained in modified, cell-seeded collagen matrices. We have now investigated the suitability of adult bone marrow mesenchymal stem cells (hMSC) for soft tissue engineering. In this study, hMSC were isolated and expanded. Cells (10(6)) were seeded onto EDC cross-linked collagen sponges and implanted in 30 immunodeficient mice. Collagen sponges without cells were used as controls. The grafts were evaluated after 2 and 6 weeks. After explantation, macroscopic appearance, weights, and histology (scaffold degradation, cellularity, and invasion depth of the seeded cells) were all assessed. After 2 and 6 weeks in vivo, new vessels were found macroscopically on all cell-seeded collagen grafts. The control grafts appeared to be degraded with a lower rate of vessel ingrowth. In the experimental group, weight gain was significant after 2 and 6 weeks in vivo compared to the same grafts after 72 h in vitro, while weight increased only slightly in the control group. Histologically, populated scaffolds showed a high density of vascularization under a capsule. The control sponges showed single capillaries and a thicker capsule. Compared to the controls, cellularity (cells/field) was greater in cell-containing collagen grafts after 2 and 6 weeks. The results obtained demonstrate that in vitro cultured human mesenchymal stem cells seeded on modified collagen sponges may be able to act as a replacement for soft tissue.