Bridging the preclinical gap: new models of endometriosis for disease and drug discovery

子宫内膜异位症是一种雌激素依赖的疾病，全世界估计有1.9亿妇女受到影响[1]。子宫内膜样病变发生在子宫外，常侵犯卵巢、肠道和腹膜壁等邻近器官。与子宫内壁相似，这些病变在激素调节下扩张和出血。炎症会导致疤痕组织和粘连的发展。对疾病病理生理学的有限了解增加了诊断的延误和生活质量的降低。虽然子宫内膜异位症可以是无症状的，但对其他人来说，它是虚弱的，表现为慢性盆腔疼痛、月经困难、疲劳和不孕。在严重情况下，可能会出现输尿管狭窄和肠梗阻等并发症。相关的工作损失和医疗费用估计为每年82亿英镑，对英国经济有重大影响[2]。目前没有一种治疗方案可以在不影响生育的情况下缓解疼痛和病变的增长。治疗通常包括止痛药、抑制卵巢功能的激素治疗和/或手术切除病变。即使在手术后，超过50%的患者由于子宫内膜异位症病变的再生或矛盾的是手术引起的纤维化而需要再次手术[3]。开发有效的治疗策略的一个主要挑战是缺乏先进的子宫内膜异位症3D共培养模型，该模型概括了不同的病变亚型，并易于操作[4]。解决这一差距对于弥合科学发现和人类应用之间的鸿沟，以满足这一重大的未得到满足的临床需求至关重要。

Endometriosis is an oestrogen-dependent condition that affects an estimated 190 million women worldwide [1]. Endometrial-like lesions form outside of the uterus and often invade adjacent organs such as the ovaries, bowel and peritoneal wall. Similar to the uterine lining, these lesions expand and bleed under hormonal regulation. Inflammation contributes to the development of scar tissue and adhesions. Limited understanding of disease pathophysiology adds to the delays in diagnosis and compromised quality of life. Whilst endometriosis can be asymptomatic, for others it is debilitating with symptoms of chronic pelvic pain, dyspareunia, fatigue and infertility. In severe cases, complications such as ureteric strictures and bowel obstruction may arise. Associated loss of work and healthcare costs, estimated at £8.2bn a year, have a significant impact on the UK economy [2].No current treatment options attenuate both pain and lesion growth without affecting fertility. Management often involves a combination of painkillers, hormone treatment that suppresses ovarian function and/ or surgical excision of lesions. Even after surgery, over 50 percent of patients require reoperation due to the regrowth of endometriosis lesions or paradoxically through surgically-induced fibrosis [3]. One major challenge to the development of effective treatment strategies is the lack of advanced 3D human co-culture models of endometriosis that recapitulate different lesion subtypes and are amenable to manipulation [4]. Addressing this gap is vital to bridge the chasm between scientific discovery and human application for this significant unmet clinical need.