School of Life Science, Faculty of Science, University of Technology Sydney, Sydney, New South Wales, Australia.
School of Chemistry and Physics, and Centre for Materials Science, Queensland University of Technology, Brisbane, Queensland, Australia.
J Cell Mol Med. 2022 Sep;26(18):4756-4767. doi: 10.1111/jcmm.17499. Epub 2022 Aug 16.
Immunoprotection and oxygen supply are vital in implementing a cell therapy for type 1 diabetes (T1D). Without these features, the transplanted islet cell clusters will be rejected by the host immune system, and necrosis will occur due to hypoxia. The use of anti-rejection drugs can help protect the transplanted cells from the immune system; yet, they also may have severe side effects. Cell delivery systems (CDS) have been developed for islet transplantation to avoid using immunosuppressants. CDS provide physical barriers to reduce the immune response and chemical coatings to reduce host fibrotic reaction. In some CDS, there is architecture to support vascularization, which enhances oxygen exchange. In this review, we discuss the current clinical and preclinical studies using CDS without immunosuppression as a cell therapy for T1D. We find that though CDS have been demonstrated for their ability to support immunoisolation of the grafted cells, their functionality has not been fully optimized. Current advanced methods in clinical trials demonstrate the systems are partly functional, physically complicated to implement or inefficient. However, modifications are being made to overcome these issues.
免疫保护和氧供对于实施 1 型糖尿病 (T1D) 的细胞治疗至关重要。如果没有这些功能,移植的胰岛细胞簇将被宿主免疫系统排斥,并且由于缺氧会发生坏死。使用抗排斥药物可以帮助保护移植细胞免受免疫系统的影响;然而,它们也可能有严重的副作用。为了避免使用免疫抑制剂,已经开发了用于胰岛移植的细胞输送系统 (CDS)。CDS 提供物理屏障以减少免疫反应,化学涂层以减少宿主纤维化反应。在一些 CDS 中,有架构来支持血管生成,从而增强氧气交换。在这篇综述中,我们讨论了当前使用 CDS 进行无免疫抑制的 T1D 细胞治疗的临床前和临床研究。我们发现,尽管 CDS 已经证明能够支持移植细胞的免疫隔离,但它们的功能尚未得到充分优化。临床试验中的当前先进方法表明,这些系统在功能上部分有效,在实施上物理上复杂或效率低下。然而,正在进行修改以克服这些问题。