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Ann Thorac Surg 2004;78:1132-1133
© 2004 The Society of Thoracic Surgeons
General Thoracic Tissue Engineering Club (LEBAO), Department of Thoracic and Vascular Surgery, Heidehaus Hospital, Hannover Medical School, Am Leineufer 70D-30419 Hannover, Germany
Department of Thoracic and Vascular Surgery, Heidehaus Hospital, Hannover Medical School, Am Leineufer 70, D-30419 Hannover, Germany
pmacchiarini{at}compuserve.com
To the Editor:
We read with interest the article by Martinod and colleagues [1]. They described the progressive transformation of an autologous aortic graft into tracheal tissue in sheep within 3 years, and concluded that the observed regenerative process could be applicable in clinical practice. An accompanying invited commentary by Mathisen [2] addressed some major clinical concerns, concluding that the "most puzzling yet intriguing aspect of their experience" was "the development of cartilaginous tracheal rings along with a membranous wall." We reinforce this concern and address some methodological issues.
First, Martinod and associates interpreted the inflammation of the transplanted aortic segment to be a stent-associated event. However, according to previous recent work[3], the observed phenomenon resembles nothing other than the degenerative process of an ischemic aortic graft. Second, the origin of the chondrocytes forming tracheal cartilage is mysterious. Are smooth muscle cells of the aortic wall able to transdifferentiate? Are chondrocytes reprogrammed by their new allotopic environment, or are they able to migratewhich has not been demonstrated scientifically by anyone else to date?
Third, Martinod and co-authors described the "appearance of cartilage" and the "formation of five to seven cartilage rings" in the transformed aortic graft. They demonstrated this important extracellular matrix remodeling process with survey hematoxylin and eosin stain and orcein. Yet, it is well known that collagen II is a major component of the tracheal extracellular matrix but scarce in vessel walls. Why did the authors not quantify the collagen II content of this matrix? It would be interesting to know which biochemical signals stimulated the chondrocytes to form cartilage rings with an intercartilage distance of 1 mm instead of a continuous tubular structure.
Fourth, the regenerative process of transplanted nonvital autogenic and xenogenic tissues has been named guided tissue regeneration in contrast to tissue engineering[4]. All these approaches want to use the regenerative potential of the organism to generate functional tissues from implanted nonvital scaffolds in vivo[5]. None of these approaches have been clinically successful. The report of Martinod and colleagues raises more questions than convincing answers. One should be cautious about taking immature preclinical concepts from the laboratory to the clinic without sophisticated scientific foundation[6].
References
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