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Ann Thorac Surg 2004;78:448-449
© 2004 The Society of Thoracic Surgeons

Invited commentary

Robert B. Cameron, MD

Department of Surgery, UCLA School of Medicine, PO Box 951741, UCLA Medical Center, Room 62-215 CHS 10833 Le Conte Ave, Los Angeles, CA 90095-1741, USA

e-mail: rcameron{at}alumni.stanford.org

This work by Walles and colleagues arises out of the perpetual desire and need for a viable tracheal substitute—the Holy Grail of tracheal surgery. While tissue engineering approaches in this area of research are not new, data are accumulating that the scaffold structure as well as the source of seed cells are important determinants of success. Due to an incomplete understanding of the interactions between growing cells and their surrounding matrix, the process of engineering tissues that blend a system of structural support and airway functionality has proven extremely challenging.

In this article the culture scaffold consists of either a mostly artificial two-dimensional or a more biologically-mimetic three-dimensional system. It is clear that chondrocytes from any source cultured in the three-dimensional system appear to proliferate and function more like normal tracheal chondrocytes, producing type II and not types III and X collagen. As noted by the authors, this is more encouraging than recent work by Lee and coworkers that report difficulty with chondrocyte viability and growth with a PLGA backbone (see reference [8] of the current article). Furthermore, tracheal and costal chondrocytes were noted to have increased cellular viability when compared with the auricular cartilage in the same three-dimensional culture system, suggesting that all sources of chondrocytes are not the same. Interestingly, the two-dimensional culture system produced better cellular proliferation but the authors attributed this to a shift toward "surplus proliferation" or what may be considered a dedifferentiated phenotype.

Although the findings of this study help inch us along to a better understanding of the processes important to the tissue engineering of tracheal substitutes, perhaps a more efficient approach would be what one would considered "permissive" tissue engineering. This approach seeks to place appropriately potent cells into an appropriately "instructive" environment that will contain all the necessary "instructions" for creation of the desired tissue. For example, instead of designing and seeding two or more populations of cell onto a complex scaffold to separately engineer a tracheal mucosa and a cartilaginous wall, cells capable of differentiating into all required cell lineages can be seeded onto a relatively generic backbone that is placed into an orthotopic position to allow the correct signaling for functional tissue generation. This possibility has been supported by the work of Huang and colleagues [1], who demonstrated that even lipoaspirate-derived stem cells are capable of chondrocytic differentiation to the degree that type II collagen, chondroitin-4-sulfate, and keratan sulfate are produced.

Regardless of the methods employed, the goal of a viable tracheal substitute certainly remains a laudable one and one worth continued exploration. The knowledge that scaffold/tissue matrix structure and cell source are important cell signaling variables in this complex process is a valuable contribution to this field. Hopefully, the authors as well as others will continue their efforts in this difficult area of research.

References

  1. Huang J.I., Zuk P.A., Jones N.F., et al. Chondrogenic potential of multipotential cells from human adipose tissue. Plast Reconstr Surg 2004;113:585-594.[Medline]




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