CHAPTER 13. Engineering an Endocrine Neo-Pancreas

Eriselda Keshi, I. Sauer, K. Hillebrandt
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Abstract

The severe short- and long-term unwanted effects and the huge economic burden of diabetes mellitus have led to immense research efforts regarding possible therapeutic modalities. Subcutaneous insulin injection and external insulin pumps, the so-called open-loop methods, albeit already established in clinical practice, are unable to maintain long-term normoglycemia. The most novel therapeutic options, summarized under the term closed-loop models, comprise pancreas transplantation, islet cell transplantation and artificial endocrine pancreas devices. Even though very promising, various obstacles hinder the translation of these concepts to the bedside. The fact that the disease only affects the endocrine pancreas and the already assembled insights into extracellular matrix and the effects its components exert on cell growth, proliferation and functionality encouraged abundant research on bioengineering an endocrine extracellular matrix-based implantable organ. Indeed, whole-organ decellularization and the subsequent perfusion recellularization of the scaffold with endothelial and islet cells has generated a new treatment alternative capable of eliminating many downsides of the exiting options. Nevertheless, further research is needed to widen our understanding of the extracellular matrix, its immunogenicity and the fundamental components on which cellular livelihood and proliferation depends, in order to achieve long-term in vitro and in vivo results.
第13章。工程内分泌新胰腺
糖尿病严重的短期和长期不良影响以及巨大的经济负担促使人们对可能的治疗方式进行大量的研究。皮下胰岛素注射和外部胰岛素泵,即所谓的开环方法,虽然已在临床实践中建立,但无法维持长期的正常血糖。在闭环模型下总结的最新颖的治疗选择包括胰腺移植、胰岛细胞移植和人工内分泌胰腺装置。尽管很有希望,但各种障碍阻碍了这些概念的临床应用。该疾病仅影响内分泌胰腺的事实,以及对细胞外基质及其成分对细胞生长、增殖和功能的影响的已有见解,鼓励了对基于内分泌细胞外基质的植入式器官的生物工程研究。事实上,全器官脱细胞和随后的内皮细胞和胰岛细胞支架灌注再细胞化已经产生了一种新的治疗方案,能够消除现有方案的许多缺点。然而,需要进一步的研究来扩大我们对细胞外基质、其免疫原性和细胞生存和增殖所依赖的基本成分的理解,以获得长期的体外和体内结果。
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