Injectable Mesenchymal Stem Cell‐Laden Matrigel Microspheres for Endometrium Repair and Regeneration

Abstract

Endometrial injury and intrauterine adhesions are increasingly reported in recent years; however, treatment options remain limited. Intravenous injection of mesenchymal stem cells (MSCs) for endometrium regeneration has limited effectiveness as the retention rate of transplanted cells is low. Hydrogel‐based tissue‐engineered solutions, such as MSC‐seeded bioscaffolds, are reported to increase retention rates; however, a less invasive alternative is still desirable. 560‐µm homogeneous Matrigel microspheres are fabricated, loading them with about 1500 MSCs and injecting them into the injured endometria of rats’ uteri. This minimally invasive procedure is proved to significantly increase endometrium thickness by over onefold after 21 d (p < 0.0001) and fertility rates from 25% to 75% in impaired and repaired uteri (p < 0.001), respectively. This study provides a minimally invasive alternative to endometrium repair with the promise to establish a broad‐spectrum technique for MSC transplantation.

Cell Culture in Microfluidic Droplets

“…282 The transplantation of MSC-Matrigel spherical microconstructs into ethanol-injured endometrium promoted tissue repair by increasing blood vessel density, reducing tissue thickness, and restoring gland cells. 286 Furthermore, rat bone marrow derived MSCs encapsulated into calcium alginate microbeads showed enhanced ectopic bone formation in vivo, 287 while the coculture of adipose tissue-derived MSCs with ostoblast encapsulated into alginatecollagen microdrops showed enhanced ectopic bone formation in comparison to MSCs without gel in rats subjected to scalp defects. 288 Alternatively, the implantation of alginate-matrigel drops laden with NSCs into a mouse spinal cord injury models promoted cellular persistence and commitment to a neural lineage within spinal cord slices, in which injury was induced by removing part of the tissue.…”

“…For instance, the intraperitoneal or subcutaneous transplantation of MSCs encapsulated into chitosan or alginate beads resulted in an increased time of cell persistence in the tissues ,, as well as increased immunomodulatory functions by promoting the resolution of inflammation in vivo . The transplantation of MSC-Matrigel spherical microconstructs into ethanol-injured endometrium promoted tissue repair by increasing blood vessel density, reducing tissue thickness, and restoring gland cells . Furthermore, rat bone marrow derived MSCs encapsulated into calcium alginate microbeads showed enhanced ectopic bone formation in vivo , while the coculture of adipose tissue-derived MSCs with ostoblast encapsulated into alginate-collagen microdrops showed enhanced ectopic bone formation in comparison to MSCs without gel in rats subjected to scalp defects .…”

Research progress of stem cell therapy for endometrial injury

“…In addition to surgical treatment, solid barriers such as intrauterine devices often cause local inflammation, and simple semi-solid barriers such as hyaluronic acid hydrogels have limited repair effect. Metformin, nitroglycerin and other drugs may increase blood flow, but their efficacy is far from ideal [ [11] , [12] , [13] , [14] ] ( Fig. 1 ).…”

“…Exosomes can act as messengers for intercellular communication and alter the fate of cells by regulating target genes [ [4] , [5] , [6] , 11 ]. Recent studies have shown that exosomes derived from stem cells, as paracrine factors, can regulate the expression of related genes in recipient cells to achieve cell and tissue regeneration [ 10 , 13 , 14 , 20 , 87 ].…”

“…Another example is that well dispersed 17β-estradiol (E 2 )-loaded PLGA microspheres (E 2 -MS) in the scaffolds, realizing the sustained release of E 2 for 21 days [ 148 ]. In addition, UC-MSCs/Matrigel microspheres with controllable particle size and cell encapsulation capacity showed a great effect on the repair and regeneration of the endometrium [ 14 ].…”