Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, United States of America.
Institute of Cellular Therapeutics, Allegheny Health Network, Pittsburgh, PA, United States of America.
Biomed Mater. 2023 Feb 17;18(2). doi: 10.1088/1748-605X/acb7bf.
Diabetes is an emerging global epidemic that affects more that 285 million people worldwide. Engineering of endocrine pancreas tissue holds great promise for the future of diabetes therapy. Here we demonstrate the feasibility of re-engineering decellularized organ scaffolds using regenerative cell source. We differentiated human pluripotent stem cells (hPSC) toward pancreatic progenitor (PP) lineage and repopulated decellularized organ scaffolds with these hPSC-PP cells. We observed that hPSCs cultured and differentiated as aggregates are more suitable for organ repopulation than isolated single cell suspension. However, recellularization with hPSC-PP aggregates require a more extensive vascular support, which was found to be superior in decellularized liver over the decellularized pancreas scaffolds. Upon continued culture for nine days with chemical induction in the bioreactor, the seeded hPSC-PP aggregates demonstrated extensive and uniform cellular repopulation and viability throughout the thickness of the liver scaffolds. Furthermore, the decellularized liver scaffolds was supportive of the endocrine cell fate of the engrafted cells. Our novel strategy to engineer endocrine pancreas construct is expected to find potential applications in preclinical testing, drug discovery and diabetes therapy.
糖尿病是一种正在全球蔓延的流行病，影响着全球超过 2.85 亿人。内分泌胰腺组织的工程学为糖尿病治疗的未来带来了巨大的希望。在这里，我们展示了使用再生细胞源对脱细胞器官支架进行再工程的可行性。我们将人类多能干细胞（hPSC）分化为胰腺祖细胞（PP）谱系，并将这些 hPSC-PP 细胞再植入脱细胞器官支架中。我们观察到，与分离的单细胞悬浮液相比，作为聚集体培养和分化的 hPSC 更适合器官再植入。然而，用 hPSC-PP 聚集体进行再细胞化需要更广泛的血管支持，而在脱细胞化的肝脏支架中发现这种支持优于脱细胞化的胰腺支架。在生物反应器中进行化学诱导的持续培养九天后，接种的 hPSC-PP 聚集体在整个肝脏支架的厚度上表现出广泛而均匀的细胞再植入和活力。此外，脱细胞化的肝脏支架支持移植细胞的内分泌细胞命运。我们构建内分泌胰腺的新型工程策略有望在临床前测试、药物发现和糖尿病治疗中找到潜在的应用。
