Human Endometrial Extracellular Matrix Hydrogel Facilitated Endometrial Mesenchymal Stem Cells for Endometrial Regeneration.

The extracellular matrix (ECM) constantly remodels to tailor a temporal spatial specific environment for the residing cells to respond to physiological or pathological stimuli. Endometrial mesenchymal stem cells (eMSC) are excellent therapeutic candidates for treating endometrial problems. In-depth investigation of the native niche to understand the regulatory mechanisms of the stem cells will enable greater translational potentials in regenerating the thin or damaged endometrium. To understand the ECM niche of eMSC, endometrial ECM from full thickness human endometrial tissues at different menstrual phases are preserved by tissue decellularization and then transformed into hydrogel material (EndoGel). EndoGel exhibits excellent compatibility with eMSC by enhancing the expansion of eMSC in vitro and facilitating the therapeutic regenerative effect in vivo evidenced by the improved fertility outcome. Comparative study of the proliferative to secretory phase EndoGel reveals unique matrisome at specific phase of the human menstrual cycle. The post-regenerated endometrium shows distinct transcriptomic profile when transplanted with different menstrual phase EndoGel, suggesting the regulatory effect of the tissue matrix is menstrual phase specific. This is the first study comparing the endometrial matrix from specific human menstrual cycle and exploring its therapeutic potentials as a supportive biomaterial for eMSC to enhance endometrial regeneration.