Purpose

To investigate if human ovarian grafting with pure virgin human recombinant collagen type-1 from bioengineered plant lines (CollPlant™) or small intestine submucosa (SIS) yields better implantation results for human ovarian tissue and which method benefits more when combined with the host melatonin treatment and graft incubation with biological glue + vitamin E + vascular endothelial growth factor-A.

Methods

Human ovarian tissue wrapped in CollPlant or SIS was transplanted into immunodeficient mice with/without host/graft treatment. The tissue was assessed by follicle counts (including atretic), for apoptosis evaluation by terminal deoxynucleotidyl transferase assay and for immunohistochemical evaluation of neovascularization by platelet endothelial cell adhesion molecule (PECAM) expression, and for identification of proliferating granulosa cells by Ki67 expression.

Results

Human ovarian tissue transplanted with CollPlant or SIS fused with the surrounding tissue and promoted neovascularization. In general, implantation with CollPlant even without additives promoted better results than with SIS: significantly higher number of recovered follicles, significantly fewer atretic follicles, and significantly more granulosa cell proliferation. Moreover, results with CollPlant alone seemed to be at least as good as those after host and graft treatments.

Conclusions

CollPlant is a biomaterial without any potential risks, and grafting ovarian tissue with CollPlant is easy and the procedure may be easily modified, with limited or no foreseeable risks, for auto-transplantation in cancer survivors. Further studies are needed using other novel methods capable of enhancing neovascularization and reducing apoptosis and follicle atresia.

中文翻译：

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用于改善人类卵巢移植的新型细胞外基质。

目的

研究用来自生物工程植物系 (ColPlant™) 或小肠粘膜下层 (SIS) 的纯原始人重组 1 型胶原蛋白移植人卵巢是否能产生更好的人卵巢组织植入结果，以及哪种方法与宿主褪黑激素治疗结合时获益更多并用生物胶+维生素E+血管内皮生长因子-A进行移植孵育。

方法

包裹在 CollPlant 或 SIS 中的人类卵巢组织被移植到免疫缺陷小鼠中，有/没有宿主/移植物治疗。通过滤泡计数（包括闭锁）评估组织，通过末端脱氧核苷酸转移酶测定法评估细胞凋亡，通过血小板内皮细胞粘附分子(PECAM) 表达对新生血管进行免疫组织化学评估，并通过 Ki67 表达鉴定增殖的颗粒细胞。

结果

用 CollPlant 或 SIS 移植的人卵巢组织与周围组织融合并促进新生血管形成。一般而言，即使没有添加剂，植入 CollPlant 也能促进比 SIS 更好的结果：恢复的卵泡数量显着增加，闭锁卵泡显着减少，颗粒细胞增殖显着更多。此外，单独使用 CollPlant 的结果似乎至少与宿主和移植物处理后的结果一样好。

结论

CollPlant 是一种没有任何潜在风险的生物材料，用 CollPlant 移植卵巢组织很容易，而且程序可以很容易地修改，风险有限或没有可预见的风险，用于癌症幸存者的自体移植。需要使用其他能够增强新血管形成和减少细胞凋亡和卵泡闭锁的新方法进行进一步研究。