Novel Synthetic Matrix Enables Miniaturized Endometrium Growth

Tufts University and MIT scientists have created a synthetic extracellular matrix (ECM) capable of nurturing the growth of miniature endometrial tissue in a controlled laboratory environment for up to two weeks. The endometrium, a crucial component of the uterine lining, has posed challenges for accurate modeling in research settings, limiting comprehensive investigations into its role in both normal physiology and disorders such as endometriosis. The study detailed in Med, introduces an ECM that provides an ideal setting for cellular interactions, closely mirroring human physiological conditions. This advancement holds the potential to empower researchers to simulate the intricate interplay between health and disease during menstrual cycles more effectively.

Juan Gnecco, the study's first author, underlines the newfound ability to utilize patient-derived samples from individuals afflicted with reproductive disorders. This approach enables a comparative analysis of organoid behavior between patients and healthy subjects. The prevailing method of growing organoids, utilizing a naturally derived hydrogel, carries inherent limitations due to its protein content that can interfere with essential cell-to-cell communication. These limitations are particularly significant when emulating the complex interplay between endometrial epithelial glands and stromal cells, which play a pivotal role in understanding how endometrial tissue transforms under the influence of sex hormones during the menstrual cycle.

The research team designed a synthetic ECM by integrating hydrogel with minimal biological signals. Human endometrial stromal and epithelial organoids were cultured within this artificial matrix, maintaining the co-culture successfully for over 15 days. Traditional methods failed to support stromal cultures and deteriorated within the same timeframe.

A notable feature of the synthetic ECM is its unique design that enables cells to generate their own matrix as they grow. Senior author Linda Griffith underscores the significance of this feature in mimicking the microenvironment experienced by cells in vivo, potentially unveiling distinctions between cells in health and disease.

Experimental validation involved subjecting co-cultures to synthetic progesterone, emulating a phase of the menstrual cycle. This manipulation led to thicker epithelial layers, heightened secretion of pro-gestational proteins, and stromal differentiation, closely paralleling changes observed in humans. Furthermore, the co-cultures were exposed to pro-inflammatory cytokines associated with endometrial disorders like endometriosis. Remarkably, in co-cultures housing both epithelial and stromal cells, cytokine exposure triggered substantial epithelial cell proliferation, echoing the abnormal growth patterns seen in endometriosis. This phenomenon was conspicuously absent in mono-cultures comprising solely epithelial cells.