Transplantation of a 3D-printed tracheal graft combined with iPS cell-derived MSCs and chondrocytes

Abstract

For successful tracheal reconstruction, tissue-engineered artificial trachea should meet several requirements, such as biocompatible constructs comparable to natural trachea, coverage with ciliated respiratory mucosa, and adequate cartilage remodeling to support a cylindrical structure. Here, we designed an artificial trachea with mechanical properties similar to the native trachea that can enhance the regeneration of tracheal mucosa and cartilage through the optimal combination of a two-layered tubular scaffold and human induced pluripotent stem cell (iPSC)-derived cells. The framework of the artificial trachea was fabricated with electrospun polycaprolactone (PCL) nanofibers (inner) and 3D-printed PCL microfibers (outer). Also, human bronchial epithelial cells (hBECs), iPSCderived mesenchymal stem cells (iPSC-MSCs), and iPSC-derived chondrocytes (iPSC-Chds) were used to maximize the regeneration of tracheal mucosa and cartilage in vivo. After 2 days of cultivation using a bioreactor system, tissue-engineered artificial tracheas were transplanted into a segmental trachea defect (1.5-cm length) rabbit model. Endoscopy did not reveal granulation ingrowth into tracheal lumen. Alcian blue staining clearly showed the formation of ciliated columnar epithelium in iPSC-MSC groups. In addition, micro-CT analysis showed that iPSC-Chd groups were effective in forming neocartilage at defect sites. Therefore, this study describes a promising approach for long-term functional reconstruction of a segmental tracheal defect.

Ionizing radiation exposure of stem cell-derived chondrocytes affects their gene and microRNA expression profiles and cytokine production

“…Findings from many recent studies suggest that hiPSCs can differentiate into various types of functional cells such as cardiomyocytes and osteocytes 7 . However, transplantation of these cells into humans presents a major risk, as the data indicate that a small number of hiPSCs remain undifferentiated at transplantation and can spontaneously transform into rapidly proliferating tumors 14 .…”

“…The most significant benefit of hiPSC-derived progenitor cells for cartilage regeneration is that they may provide an unlimited supply of chondrogenic cells for in vivo applications. Consequently, cell-based therapy has been recognized as a potentially effective approach to healing tracheal cartilage 7 . Imaizumi et al 8 suggested that hiPSCs could be a new cell source to regenerate tracheal cartilage.…”

Mesenchymal Stem Cell and MicroRNA Therapy of Musculoskeletal Diseases

“…When iPSC-MSCs were Injected into musculoskeletal injured areas, including osteoarthritis mainly, bone fracture, osteochondritis, and tendonitis in horses, the results indicated the improvement of these defects by reducing lameness and fever without any adverse effects (10). Taken together, iPSC-MSCs are considered as powerful tools for regenerative medicine than any other tissue-derived MSCs (101,102).…”

Current Advances in 3D Bioprinting Technology and Its Applications for Tissue Engineering

“…The mechanical properties of the engineered tracheal structure were similar to those of native tissue. Recently, Kim et al printed a two-layered hollow structure using electrospun 3D bioprinters [ 176 ]. The inner layer was made of nanoscale PCL fibers, and the outer layer consisted of microscale PCL fibers.…”