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Abstract

Dr Haider and colleagues wrote that “the authors based their observation solely on the expression of x-gal staining, which would have been more conclusive with evidence of the absence of immune cell infiltration at the site of the graft.” In fact, that can be seen in our Figure 4 [1Saito T. Kuang J.-Q. Bittira B. Al-Khaldi A. Chiu R.C.-J. Xenotransplant cardiac chimera immune tolerance of adult stem cells.Ann Thorac Surg. 2002; 74: 19-24Abstract Full Text Full Text PDF PubMed Scopus (232) Google Scholar]. One day after ligation of the left anterior descending coronary artery [LAD], the infarct site underwent necrosis with inflammatory cell infiltration as expected. Because LAD was occluded, the recruited bone marrow stromal cells (MSCs) initially reached the viable zone around the infarcted area by way of collaterals (Figs 4C, 4D). This zone clearly showed the absence of cellular infiltration attacking the labeled mouse MSCs. In our follow-up control study (unpublished data), we injected differentiated cutaneous fibroblasts from the same mouse donor into the rat heart and confirmed a rapid cellular infiltration response against the implanted cells and elimination of the labeled fibroblasts within several days. These observations are consistent with our interpretation that the MSCs possess unique immune tolerance, as we discussed in our report [1Saito T. Kuang J.-Q. Bittira B. Al-Khaldi A. Chiu R.C.-J. Xenotransplant cardiac chimera immune tolerance of adult stem cells.Ann Thorac Surg. 2002; 74: 19-24Abstract Full Text Full Text PDF PubMed Scopus (232) Google Scholar].It was not feasible to accurately quantitate the number of cells reaching the myocardium because of their distribution within the myocardium. Furthermore, as we demonstrated, the labeled cells did not all differentiate into neo-cardiomyocytes, but also became cells of other phenotypes. A technique that can reliably quantitate not only the labeled cells in the myocardium but also the number of differentiated cells of specific phenotype and their topological distribution would be highly valuable, as establishment of a dose–response relationship (ie, number of cells versus functional improvement) would be very important clinically.Finally, our choice of the cellular xenotransplant model to study myocardial regeneration is not meant to imply that xenotransplantation is preferable to allotransplantation clinically. Our intent was to “push the envelope” to see how the MSCs would respond in this immunologically even more hostile environment. Dr Haider and colleagues wrote that “the authors based their observation solely on the expression of x-gal staining, which would have been more conclusive with evidence of the absence of immune cell infiltration at the site of the graft.” In fact, that can be seen in our Figure 4 [1Saito T. Kuang J.-Q. Bittira B. Al-Khaldi A. Chiu R.C.-J. Xenotransplant cardiac chimera immune tolerance of adult stem cells.Ann Thorac Surg. 2002; 74: 19-24Abstract Full Text Full Text PDF PubMed Scopus (232) Google Scholar]. One day after ligation of the left anterior descending coronary artery [LAD], the infarct site underwent necrosis with inflammatory cell infiltration as expected. Because LAD was occluded, the recruited bone marrow stromal cells (MSCs) initially reached the viable zone around the infarcted area by way of collaterals (Figs 4C, 4D). This zone clearly showed the absence of cellular infiltration attacking the labeled mouse MSCs. In our follow-up control study (unpublished data), we injected differentiated cutaneous fibroblasts from the same mouse donor into the rat heart and confirmed a rapid cellular infiltration response against the implanted cells and elimination of the labeled fibroblasts within several days. These observations are consistent with our interpretation that the MSCs possess unique immune tolerance, as we discussed in our report [1Saito T. Kuang J.-Q. Bittira B. Al-Khaldi A. Chiu R.C.-J. Xenotransplant cardiac chimera immune tolerance of adult stem cells.Ann Thorac Surg. 2002; 74: 19-24Abstract Full Text Full Text PDF PubMed Scopus (232) Google Scholar]. It was not feasible to accurately quantitate the number of cells reaching the myocardium because of their distribution within the myocardium. Furthermore, as we demonstrated, the labeled cells did not all differentiate into neo-cardiomyocytes, but also became cells of other phenotypes. A technique that can reliably quantitate not only the labeled cells in the myocardium but also the number of differentiated cells of specific phenotype and their topological distribution would be highly valuable, as establishment of a dose–response relationship (ie, number of cells versus functional improvement) would be very important clinically. Finally, our choice of the cellular xenotransplant model to study myocardial regeneration is not meant to imply that xenotransplantation is preferable to allotransplantation clinically. Our intent was to “push the envelope” to see how the MSCs would respond in this immunologically even more hostile environment.