Epithelial cell therapies have been at an impasse because of inefficient methods of transplantation to solid organs. Patch grafting strategies were established enabling transplantation of ≥10^7th organoids/patch of porcine GFP+ biliary tree stem/progenitors into livers of wild type hosts. Grafts consisted of organoids embedded in soft (~100 Pa) hyaluronan hydrogels, both prepared in serum-free Kubota's Medium; placed against target sites; covered with a silk backing impregnated with more rigid hyaluronan hydrogels (~700 Pa); and use of the backing to tether grafts with sutures or glue to target sites. Hyaluronan coatings (~200–300 Pa) onto the serosal surface of the graft served to minimize adhesions with neighboring organs. The organ's clearance of hyaluronans enabled restoration of tissue-specific paracrine and systemic signaling, resulting in return of normal hepatic histology, with donor parenchymal cells uniformly integrated amidst host cells and that had differentiated to mature hepatocytes and cholangiocytes. Grafts containing donor mature hepatocytes, partnered with endothelia, and in the same graft biomaterials as for stem/progenitor organoids, did not engraft. Engraftment occurred if porcine liver-derived mesenchymal stem cells (MSCs) were co-transplanted with donor mature cells. RNA-seq analyses revealed that engraftment correlated with expression of matrix-metalloproteinases (MMPs), especially secreted isoforms that were found expressed strongly by organoids, less so by MSCs, and minimally, if at all, by adult cells.

Engraftment with patch grafting strategies occurred without evidence of emboli or ectopic cell distribution. It was successful with stem/progenitor organoids or with cells with a source(s) of secreted MMP isoforms and offers significant potential for enabling cell therapies for solid organs.

由于移植到实体器官的方法效率低下，上皮细胞疗法一直处于僵局。建立了补丁移植策略，能够将≥10^{个第 7}类器官/补丁猪 GFP+ 胆管树干/祖细胞移植到野生型宿主的肝脏中。移植物由类器官组成嵌入软 (~100 Pa) 透明质酸水凝胶中，均在无血清 Kubota 培养基中制备；针对目标站点放置；覆盖着浸渍有更坚硬的透明质酸水凝胶 (~700 Pa) 的丝绸背衬；并使用背衬将移植物用缝线或胶粘到目标部位。移植物的浆膜表面上的透明质酸涂层（~200-300 Pa）用于最大限度地减少与邻近器官的粘连。该器官对透明质酸的清除使组织特异性旁分泌和全身信号传导得以恢复，导致肝组织学恢复正常，供体实质细胞均匀整合在宿主细胞中，并已分化为成熟的肝细胞和胆管细胞。含有供体成熟肝细胞的移植物，与内皮细胞合作，并在同一个移植物中至于干/祖类器官的生物材料，没有移植。如果猪肝来源的间充质干细胞 (MSCs) 与供体成熟细胞共同移植，则会发生植入。RNA-seq 分析表明，植入与基质金属蛋白酶 (MMP) 的表达相关，尤其是在类器官中强烈表达的分泌型亚型，在 MSC 中表达较少，在成体细胞中表达最少。

在没有栓子或异位细胞分布证据的情况下，采用补片移植策略进行植入。它在干细胞/祖细胞类器官或具有分泌 MMP 同种型来源的细胞上取得了成功，并为实体器官的细胞疗法提供了巨大的潜力。