Campo Hannes, Baptista Pedro M, López-Pérez Nuria, Faus Amparo, Cervelló Irene, Simón Carlos
Fundación Instituto Valenciano de Infertilidad, Department of Obstetrics and Gynecology, School of Medicine, Valencia University and Instituto Valenciano de Infertilidad/INCLIVA, Valencia, Spain.
Instituto Aragonés de Ciencias de la Salud, Zaragoza, Spain.
Biol Reprod. 2017 Jan 1;96(1):34-45. doi: 10.1095/biolreprod.116.143396.
Absolute uterine factor infertility, or the absence of a functional uterus, has a prevalence of 3%-5% in the general population. Despite the great strides being made in reproductive medicine, patients diagnosed with absolute uterine factor infertility remain untreatable. The only available solution has been gestational surrogacy, but recently the Brannström group presented a viable alternative by reporting the first successful live birth after uterus transplantation. Similar to other transplantations, this approach has inherent limitations such as the paucity of donor organs and the need for long-term immunosuppression. Whole organ de- and recellularization, a novel tissue engineering approach within the field of regenerative medicine, could eventually provide another solution. Several groups have described animal models in which they have performed decellularization of whole uteri, while maintaining the extracellular matrix to enable recellularization attempts. Our work offers a new perspective; in decellularizing the porcine uterus, this constitutes the first pilot study using large whole reproductive organs. We demonstrated the preservation of a reusable/functional extracellular matrix while maintaining its vascular network. Furthermore, we report the first use of human side population stem cells in the successful recellularization of small acellular disk scaffolds procured from the decellularized organs. To conclude, this research opens new avenues in whole uterus bioengineering, opening the way towards the transplantation of functional bioengineered uteri into humans.
绝对子宫因素不孕症，即子宫功能缺失，在普通人群中的患病率为3% - 5%。尽管生殖医学取得了巨大进展，但被诊断为绝对子宫因素不孕症的患者仍然无法治疗。唯一可行的解决办法是妊娠代孕，但最近布兰斯特伦团队报告了子宫移植后首例成功的活产案例，提出了一种可行的替代方案。与其他移植手术一样，这种方法存在固有的局限性，如供体器官稀缺以及需要长期免疫抑制。全器官去细胞化和再细胞化是再生医学领域一种新型的组织工程方法，最终可能提供另一种解决方案。几个研究小组已经描述了动物模型，他们在这些模型中对整个子宫进行了去细胞化处理，同时保留细胞外基质以尝试进行再细胞化。我们的工作提供了一个新的视角；在对猪子宫进行去细胞化处理时，这是首次使用大型整个生殖器官的初步研究。我们证明了在保留血管网络的同时，保存了可重复使用/功能性的细胞外基质。此外，我们报告了首次使用人侧群干细胞成功地对从去细胞化器官获得的小型无细胞圆盘支架进行再细胞化。总之，这项研究为全子宫生物工程开辟了新途径，为将功能性生物工程子宫移植到人类体内铺平了道路。
