Tissue engineering of human myometrium

描述（由申请人提供）：我们打算在三维空间中培养人类子宫组织（子宫肌层）。我们将使用一种新型的支架形成技术，然后将细胞接种到支架中。这些结构将被做得足够大以模拟正常的人类子宫肌层。该项目还将证明这种工程组织的功能与正常组织相似。我们将证明工程组织条能够收缩，工程子宫能够产生腔内压力。我们将开发组织工程作为研究妊娠人类子宫收缩的新模型。该模型将解决子宫功能异常的主要健康问题（如早产、产后出血和过期妊娠）。该模型的新奇在于细胞基因表达和三维物理结构都能够被控制。我们将从剖腹产妇女的子宫组织开始。我们将通过使用标准培养技术培养细胞来扩增细胞数量。我们将用壳聚糖制造支架，壳聚糖是一种容易获得的、天然存在的、安全的、生物可吸收的化合物。这些支架可以制成几乎任何形状，并具有各种各样的孔隙率以支持细胞生长。我们将测定细胞在支架内和支架周围生长的速率。我们将比较在正常子宫组织和工程组织中发现的生化标志物。我们将比较工程组织条和最近从妇女身上取出的组织条的生理学。我们将首次展示组织工程子宫腔内压力的产生。除了为研究组织水平和器官水平的子宫功能创造新的范例之外，这些技术还能够被放大以允许从来自患者的小平滑肌样本创建组织贴片。该项目是为出生时没有功能性子宫的妇女或已进行子宫切除术的妇女创造整个替代子宫的第一步。公共卫生相关性：组织工程子宫肌层将由人类子宫细胞和壳聚糖制成，壳聚糖是一种天然存在的可吸收支架材料。组织工程化子宫肌层将成为研究子宫肌层收缩性的新模型。该项目将是为出生时子宫异常或子宫切除术后的妇女构建功能性替代子宫的第一步。

DESCRIPTION (provided by applicant): We intend to grow human uterine tissue (myometrium) in three dimensions. We will use a novel scaffold-forming technique, and then seed cells into the scaffold. These structures will be made large enough to mimic normal human myometrium. This project will also demonstrate that this engineered tissue will function similarly to the normal tissue. We will show that the engineered tissue strips are capable of contracting, and the engineered uterus is capable of generating intracavitary pressure. We will develop tissue engineering as a new model for the study of contractions of the pregnant human uterus. This model will address major health questions of abnormal uterine function (such as preterm labor, post partum hemorrhage, and post-dates pregnancy). The novelty of the model is that both cellular gene expression and 3-D physical structure are capable of being controlled. We will start with human uterine tissue obtained from women at the time of Cesarean Delivery. We will amplify the number of cells by growing them using standard culture techniques. We will create scaffolds from chitosan, a readily available, naturally occurring, safe, bio-resorbable compound. These scaffolds can be made in virtually any shape and with a wide variety of porosities to support cell growth. We will determine the rates that cells grow into and around the scaffolds. We will compare the biochemical markers found in normal uterine tissue with those in the engineered tissue. We will compare the physiology of engineered tissue strips with strips recently removed from women. We will demonstrate, for the first time, generation of intracavitary pressure from a tissue-engineered uterus. In addition to creating a new paradigm for study of tissue-level and organ-level uterine function, these techniques are capable of being up-scaled to allow tissue patches to be created from a small smooth muscle sample from a patient. This project is the first step on the path to creating an entire replacement uterus for women born without a functional uterus, or who have had a hysterectomy. PUBLIC HEALTH RELEVANCE: Tissue-engineered myometrium will be made from human uterine cells and chitosan, a naturally occurring, resorbable scaffold material. The tissue-engineered myometrium will be a novel model for the study of myometrial contractility. This project will be the first step toward construction of a functional replacement uterus for women who were born with a uterine anomaly or have had a hysterectomy.