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Introduction: Despite progress in whole-organ decellularization and recellularization, maintaining long-term perfusion in vivo remains a hurdle to realizing clinical translation of bioengineered kidney grafts. The objectives for the present study were to define a threshold glucose consumption rate (GCR) that could be used to predict in vivo graft hemocompatibility and utilize this threshold to assess the in vivo performance of clinically relevant decellularized porcine kidney grafts recellularized with human umbilical vein endothelial cells (HUVECs). Materials and methods: Twenty-two porcine kidneys were decellularized and 19 were re-endothelialized using HUVECs. Functional revascularization of control decellularized (n = 3) and re-endothelialized porcine kidneys (n = 16) was tested using an ex vivo porcine blood flow model to define an appropriate metabolic glucose consumption rate (GCR) threshold above which would sustain patent blood flow. Re-endothelialized grafts (n = 9) were then transplanted into immunosuppressed pigs with perfusion measured using angiography post-implant and on days 3 and 7 with 3 native kidneys used as controls. Patent recellularized kidney grafts underwent histological analysis following explant. Results: The glucose consumption rate of recellularized kidney grafts reached a peak of 39.9 ± 9.7 mg/h at 21 ± 5 days, at which point the grafts were determined to have sufficient histological vascular coverage with endothelial cells. Based on these results, a minimum glucose consumption rate threshold of 20 mg/h was set. The revascularized kidneys had a mean perfusion percentage of 87.7% ± 10.3%, 80.9% ± 33.1%, and 68.5% ± 38.6% post-reperfusion on Days 0, 3 and 7, respectively. The 3 native kidneys had a mean post-perfusion percentage of 98.4% ± 1.6%. These results were not statistically significant. Conclusion: This study is the first to demonstrate that human-scale bioengineered porcine kidney grafts developed via perfusion decellularization and subsequent re-endothelialization using HUVEC can maintain patency with consistent blood flow for up to 7 days in vivo. These results lay the foundation for future research to produce human-scale recellularized kidney grafts for transplantation.
RESUMO
English-monolingual children develop a shape bias early in language acquisition, such that they more often generalize a novel label based on shape than other features. Spanish-monolingual children, however, do not show this bias to the same extent (Hahn & Cantrell, 2012). Studying children who are simultaneously learning both Spanish and English presents a unique opportunity to further investigate how this word-learning bias develops. Thus, we asked how Spanish-English bilingual children (Mage = 21.31 months) perform in a novel-noun generalization (NNG) task, specifically examining how past language experience (i.e. language exposure and vocabulary size) and present language context (i.e. whether the NNG task was conducted in Spanish or English) influence the strength of the shape bias. Participants completed the NNG task either entirely in English (N = 16) or entirely in Spanish (N = 16), as well as language understanding tasks in both English and Spanish to ensure that they understood what the experimenter was asking them to do. Parents completed a language exposure survey and vocabulary checklists in Spanish and English. There was a significant interaction between condition and choice type: Bilingual children in the English condition showed a shape bias in the NNG task, but bilingual children in the Spanish condition showed no reliable biases. No measures of past language experience were related to NNG task performance. These results suggest that when learning new words, bilingual children are attuned to the regularities of the present language context, and prior language experiences may play a more secondary role.
