CSIR-Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad, 500007, India.
Tissue Eng Regen Med. 2021 Feb;18(1):99-112. doi: 10.1007/s13770-020-00296-y. Epub 2020 Oct 24.
Tissue engineering centers on creating a niche similar to the natural one, with a purpose of developing an organ construct. A natural scaffold can replace none while creating a scaffold unique to each tissue in composition, architecture and cues that regulate the character of cells.
Whole pancreas from mouse was decellularized using detergent and enzymes, followed by recellularizing with MSC from human placenta. This construct was transplanted in streptozotocin induced diabetic mice. Histopathology of both decellularized and recellularized transplanted pancreas and qPCR analysis were performed to assess its recovery.
Decellularization removes the cells leaving behind extracellular matrix rich natural scaffold. After reseeding with mesenchymal stem cells, these cells differentiate into pancreas specific cells. Upon transplantation in streptozotocin induced diabetic mice, this organ was capable of restoring its histomorphology and functioning. Restoration of endocrine (islets), the exocrine region (acinar) and vascular network was seen in transplanted pancreas. The process of functional recovery of endocrine system took about 20 days when the mice start showing blood glucose reduction, though none achieved gluconormalization.
Natural decellularized scaffolds of soft organs can be refunctionalized using recipient's mesenchymal stem cells to restore structure and function; and counter immune problems arising during transplantation.
组织工程的核心是创造一个类似于自然的小生境,目的是开发一种器官构建体。天然支架在组成、结构和调节细胞特性的信号方面是无法替代的,而每个组织都有其独特的支架。
使用去污剂和酶从鼠的整个胰腺中进行脱细胞处理,然后用人胎盘来源的 MSC 再细胞化。将该构建体移植到链脲佐菌素诱导的糖尿病小鼠中。对脱细胞和再细胞化移植胰腺进行组织病理学检查,并进行 qPCR 分析,以评估其恢复情况。
脱细胞去除了细胞,留下富含细胞外基质的天然支架。再接种间充质干细胞后,这些细胞分化为胰腺特异性细胞。将其移植到链脲佐菌素诱导的糖尿病小鼠中,该器官能够恢复其组织形态和功能。在移植的胰腺中可以看到内分泌(胰岛)、外分泌区(腺泡)和血管网络的恢复。当小鼠开始出现血糖降低时,内分泌系统的功能恢复过程大约需要 20 天,但没有一个达到正常血糖水平。
使用受者的间充质干细胞可以使软器官的天然脱细胞支架重新发挥功能,从而恢复结构和功能;并解决移植过程中出现的免疫问题。