Tissue-engineered spleen protects against overwhelming pneumococcal sepsis in a rodent model.

ABSTRACT

BACKGROUND/PURPOSE: Solid organs production is an ultimate goal of tissue engineering. After refining a technique for intestinal engineering, we applied it to a solid organ, the spleen. Overwhelming postsplenectomy sepsis results in death in nearly half of all cases. This risk is pronounced in children. Necrosis of autotransplanted spleen slices occurs prior to regeneration. We postulate that tissue engineering techniques might be superior. METHODS: Four groups of Lewis rats were compared sham laparotomy, tissue-engineered spleen (TES), traditional spleen slices, and splenectomy. TES was generated from splenic units, multicellular components of juvenile spleen implanted on a biodegradable polymer scaffold, and spleen slices were derived from age-matched juveniles. Pneumococcal sepsis was induced at wk 16, and survival curves were constructed. RESULTS: Tissue-engineered spleen protected against pneumococcal septicemia with a survival proportion of 85.7% compared with 41.17% of splenectomized animals. Spleen slice was also protective with 71.43% survival. Compared with splenectomy, control and TES groups were statistically significant (P = 0.0002, P = 0.0087; hazard ratio of splenectomy = 5.493) and the Slice group was nearly statistically significant (P = 0.0642, hazard ratio of splenectomy = 2.673). CONCLUSIONS: TES is a novel application of tissue engineering to splenic regeneration and creates a functional spleen. This approach could be advantageous in severe pediatric trauma.