Thymus-Derived Mesenchymal Stem Cells for Tissue Engineering Clinical-Grade Cardiovascular Grafts

Abstract

Mesenchymal stem cells (MSCs) are attractive tools for regenerative medicine because of their multidifferentiation potential and immunomodulation capacity. In congenital heart defect surgical correction, replacement grafts lacking growth potential are commonly used. Tissue engineering promises to overcome the limitations of these grafts. In this study, we hypothesized that human thymus-derived MSCs are a suitable tool to tissue engineer a living vascular graft with good integration and patency once implanted in vivo. Human thymus-derived MSCs (hT-MSCs) were identified by the expression of MSC markers and mesenchymal differentiation potential. When cultured onto natural scaffold to produce tissue-engineered graft, hT-MSCs exhibited great proliferation potential and the ability to secrete their own extracellular matrix. In addition, when implanted in vivo in a piglet model of left pulmonary grafting, the engineered graft exhibited good integration within the host tissue, indicating potential suitability for corrective cardiovascular surgery. The optimized xeno-free, good manufacturing practices-compliant culture system proved to be optimum for large-scale expansion of hT-MSCs and production of tissue-engineered cardiovascular grafts, without compromising the quality of cells. This study demonstrated the feasibility of engineering clinical-grade living autologous replacement grafts using hT-MSCs and proved the compatibility of these grafts for in vivo implantation in a left pulmonary artery position.

Amnion-Based Scaffold with Enhanced Strength and Biocompatibility for In Vivo Vascular Repair

“…Furthermore, its tensile strength improved significantly when it was dried and layered. and some adventitia [32], [45]. Similar results were obtained by using synthetic scaffolds seeded with bone marrow mononuclear cells [46].…”

“…Mesenchymal stem cells (MSCs) have been isolated from multiple sources such as bone marrow and adipose tissue [29]. Critically for congenital heart defect repair, MSCs have also been isolated from cord blood and thymus tissue [30]- [32]. MSCs are promising for seeding onto scaffolds as part of a tissue engineered construct for cardiac repair because of their multilineage differentiation potential, ability to regulate the immune response, and because they do not cause teratomas [33]- [35].…”

Successful Reconstruction of the Right Ventricular Outflow Tract by Implantation of Thymus Stem Cell Engineered Graft in Growing Swine

“…Once implanted in vivo, an ideal biofunctional graft is remodeled and eventually replaced by the host’s own extracellular matrix (1). Several cell types have been used for cardiac tissue engineering, including mesenchymal stem cells (MSCs) (2), induced pluripotent stem cells (3), endothelial cells (ECs) (4), and pericytes (5). In particular, MSCs are a preferred choice because of their immune-privileged nature, multilineage differentiation potential, and ability to promote tissue healing by paracrine mechanisms 6, 7.…”

Thymus Regeneration and Future Challenges

“…The thymic stroma contains dendritic cells, macrophages, epithelial, mesenchymal and vascular elements [9][10][11][12][13][14]. In this multicellular structure with different cell types and functions several minor stem cell populations can be found, in particular thymic epithelial progenitor cells/thymic epithelial stem cells (TEPC/TESC) [15, 16•], mesenchymal stem cells (MSC) [17,18] and lymphoid progenitor cells (LPC) [12,[19][20][21][22][23][24]. Of these, thymic epithelial cells (TEC) provide most of the specialist functions of the organ [25,26].…”