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A2677 - Potential of Adipose-Derived Stem/Stromal Cells for Lung Transplantation and Lung Tissue Engineering
Author Block: T. Tsuchiya, R. Doi, H. Watanabe, K. Matsumoto, T. Miyazaki, R. Kamohara, G. Hatachi, K. Tomoshige, N. Yamasaki, T. Nagayasu; Surgical Oncology, Nagasaki University, Nagasaki, Japan.
Adipose-derived stem/stromal cells (ADMSCs) are multipotent cells that can differentiate into a variety of cell types, which have equal differentiative potential compared to bone marrow-derived mesenchymal stem cells, and provide a more easily accessible and abundant cell source. Here we outline the benefits of ADMSCs in our rat lung study models, including immunomodulatory effects for lung transplantation and regenerative effects for lung tissue engineering, and summarize the mechanisms as it relates to clinical use. In the rat lung transplantation model, isogenic ADMSCs were intravenously administered immediately following orthotopic left lung transplantation. The experimental subjects were divided into four groups: 1) Control group; no administration following transplantation, 2) ADMSCs group; a single intravenous injection of ADMSCs following transplantation, 3) Tacrolimus group; tacrolimus (0.5 mg/kg) administration every 24 hours following transplantation; and 4) ADMSCs and Tacrolimus group; a single intravenous injection of ADMSCs in combination with tacrolimus administration every 24 hours following transplantation. The results showed, the histological rejection grade in ADMSCs and Tacrolimus group proved significantly lower than that in the Tacrolimus group. The serum levels of hepatocyte growth factor and the expression of cMet in ADMSCs and Tacrolimus group was also significantly higher when compared to the lung grafts of Tacrolimus group. These results suggest that ADMSCs have an immunosuppressive effect when co-administered with tacrolimus. In the rat lung tissue engineering model, vascular networks were regenerated in the decellularized scaffold using isogenic ADMSCs and rat lung microvessel endothelial cells (RLMVECs). The re-endothelialized scaffolds were maintained ex vivo under vascular flow for 8 to 16 days, and then, cell morphology, differentiation, location and viability were examined. Pathologies of the bioengineered lungs were assessed in vivo transplantation models. The results showed, seeded ADMSCs contributed to endothelial cell survival and PCR array analysis revealed significantly enhanced angiogenesis related genes compared to the RLMVECs-alone group. ADMSCs also exhibit a perivascular phenotype in the repopulated pulmonary vasculature. Cell tracking studies indicated that ADMSCs stabilized regenerated blood vessels. In vivo vascular permeability was improved in the transplanted bioengineered lungs with RLMVECs pulse ADMSCs. The results indicate that ADMSCs stabilized regenerated pulmonary vessels facilitated the alveolar capillary barrier functions as perivascular cells, suggesting that ADMSCs might be an essential cell source for vascular regeneration in the bioengineered lung. In summary, ADMSCs administration may be beneficial as a therapeutic approach during lung transplantation as well in the creation of lung biomaterials.