Children's Hospital Los Angeles, Keck School of Medicine of the University of Southern California, Division of Pediatric Surgery, 4650 Sunset Boulevard Mailstop #35, Los Angeles, CA 90027, USA.
Regen Med. 2012 Nov;7(6):807-18. doi: 10.2217/rme.12.91.
Loss of colon reservoir function after colectomy can adversely affect patient outcomes. In previous work, human fetal intestinal cells developed epithelium without mesenchyme following implantation in mice. However, for humans, postnatal tissue would be the preferred donor source. We generated tissue-engineered colon (TEC) from postnatal human organoid units.
MATERIALS & METHODS: Organoid units were prepared from human colon waste specimens, loaded onto biodegradable scaffolds and implanted into immunocompromised mice. After 4 weeks, human TEC was harvested. Immunofluorescence staining confirmed human origin, identified differentiated epithelial cell types and verified the presence of supporting mesenchyme.
Human TEC demonstrated a simple columnar epithelium. Immunofluorescence staining demonstrated human origin and the three differentiated cell types of mature colon epithelium. Key mesenchymal components (smooth muscle, intestinal subepithelial myofibroblasts and ganglion cells) were seen.
Colon can form from human progenitor cells on a scaffold in a mouse host. This proof-of-concept experiment is an important step in transitioning TEC to human therapy.
结肠切除后结肠储袋功能丧失会对患者的预后产生不利影响。在之前的研究中，人类胎儿肠细胞在植入小鼠体内后可在没有间质的情况下发育为肠上皮。然而，对于人类来说，更倾向于使用来自于出生后的组织作为供体来源。我们从人源类器官单位中构建了组织工程化结肠（TEC）。
类器官单位从人结肠废弃标本中制备，装载到生物可降解支架上，然后植入免疫缺陷小鼠体内。4 周后，收获人 TEC。免疫荧光染色证实了其人类起源，鉴定了成熟结肠上皮的三种分化细胞类型，并证实了支持性间质的存在。
人 TEC 表现出简单的柱状上皮。免疫荧光染色证实了其人类起源以及三种成熟结肠上皮的分化细胞类型。还观察到关键的间质成分（平滑肌、肠黏膜下肌纤维母细胞和神经节细胞）。
结肠可以在小鼠宿主的支架上由人祖细胞形成。该概念验证实验是将 TEC 过渡到人体治疗的重要步骤。
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