Tracheal cartilage regeneration by progenitor cells derived from the perichondrium

The regenerative potential of adult tracheal cartilage is very limited which makes repair of this cartilage extremely challenging. However, the perichondrium has a large quantity of progenitor cells that differentiate directly into chondrocytes. Bone morphogenetic protein (BMP) stimulates chondrogenesis by inducing the differentiation of progenitor cells into chondrocytes which makes it a potential therapeutic agent for cartilage regeneration. In this present study, we investigated the mesenchymal stem cell characterization of progenitor cells from the perichondrial tissue of tracheal cartilage and the efficiency of the perichondrium for tracheal cartilage regeneration by evaluating the effect of BMP on cartilage regeneration in perichondrial progenitor cells. Progenitor cells were isolated from the fibrous perichodrial tissue of tracheal cartilage and cultured for phenotypic characterization of mesenchymal stem cells. Next, a 0.3–0.5 mm gap was made in the mid-ventral portion of the tracheal cartilages. In the control group (n=5), the resulting gap was left untreated (without perichondrial replacement). In the perichondrial group (n=15), the gap was replaced by fibrous perichondrial tissue. We euthanized all mice in each group (n=5) at 2, 4, and 20 weeks after the perichondrial replacement and examined the replacement site microscopically. The immunohistochemistry for BMP-2 was performed in progenitor cells from perichondrial tissue. The primary cultured cells from fibrous perichondrial tissue were positive for CD29, CD90, and CD105, but negative for CD45. The progenitor cells were capable of multipotent differentiation towards adipogenic and osteogenic lineages. The control group showed no regenerated cartilage 2 weeks after injury. The experimental group demonstrated proliferation of progenitor cells between both stumps at 2 weeks and regenerated hyaline cartilage was observed at 4 and 20 weeks. Regenerated cartilage was observed as separated islets between the ends of the host cartilage stumps. The gaps were nearly filled with regenerated cartilage at 20 weeks. BMP-2 was expressed in both fibrous and cabial perichondria chondrogenesis. The progenitor cells from perichondrial tissue had mesenchymal stem cell-like features and might play a crucial role in tracheal cartilage regeneration and repair. Expression of BMP-2 may induce formation of structural cartilage in a tracheal injury model.