Hyaluronic Acid Hydrogel Integrated with Mesenchymal Stem Cell‐Secretome to Treat Endometrial Injury in a Rat Model of Asherman's Syndrome

Abstract

Stem cell therapies have made strides toward the efficacious treatment of injured endometrium and the prevention of intrauterine adhesions, or Asherman's syndrome (AS). Despite this progress, they are limited by their risk of tumor formation, low engraftment rates, as well as storage and transportation logistics. While attempts have been made to curb these issues, there remains a need for simple and effective solutions. A growing body of evidence supports the theory that delivering media, conditioned with mesenchymal stem cells, might be a promising alternative to live cell therapy. Mesenchymal stem cell‐secretome (MSC‐Sec) has a superior safety profile and can be stored without losing its regenerative properties. It is versatile enough to be added to a number of delivery vehicles that improve engraftment and control the release of the therapeutic. Thus, it holds great potential for the treatment of AS. Here, a new strategy for loading crosslinked hyaluronic acid gel (HA gel) with MSC‐Sec is reported. The HA gel/MSC‐Sec treatment paradigm creates a sustained release system that repairs endometrial injury in rats and promotes viable pregnancy.

Biomaterials Functionalized with MSC Secreted Extracellular Vesicles and Soluble Factors for Tissue Regeneration

“…[ 17,18 ] The MSC secretome can be collected in vitro as MSC‐conditioned media (MSC‐CM) and comprises both soluble factors, including cytokines, chemokines, and growth factors, [ 19 ] as well as vesicular secretions termed extracellular vesicles (EVs). [ 20 ] MSC‐CM enhances in vitro cell proliferation, [ 21–23 ] migration, [ 22,24 ] angiogenesis, [ 25 ] and imparts anti‐apoptotic [ 23,25 ] and anti‐inflammatory [ 26 ] effects. In vivo, MSC‐CM has demonstrated healing in diverse preclinical indications including cutaneous wounds, [ 22 ] Parkinson's disease, [ 27 ] liver failure, [ 28 ] and myocardial infarction (MI).…”

Advances in the Application of Biomimetic Endometrium Interfaces for Uterine Bioengineering in Female Infertility

“…In addition to bioactive proteins, some researches focused on the secreted extracellular vesicles from stem cells for uterus repair (Zhang Y. et al, 2016;Azizi et al, 2018). Liu et al (2019b) innovatively created stem cell secretome modified-HA hydrogel that increased release of a number of regenerationrelated growth factors, such as epidermal growth factor (EGF), FGF, IGF-1, and IGF binding protein (IGFBP). The crosslinked HA gel served as a carrier and prolonged the in vivo retention time of stem cell secretome, thus leading to thicker endometrium and more glands compared to gel application only.…”

Preventive Effects of Intrauterine Injection of Bone Marrow-Derived Mesenchymal Stromal Cell-Conditioned Media on Uterine Fibrosis Immediately after Endometrial Curettage in Rabbit

“…Several methods have been developed for the treatment of uterine fibrosis, with surgical intervention using hysteroscopy to remove the adherent tissue inside the uterine cavity being the first option [ 2 ]. Recently, mesenchymal stromal/stem cell therapy [ 3 ] and mesenchymal stromal/stem cell-derived macrovesicle injection [ 4 , 5 ] have been recommended for the treatment of uterine fibrosis. There is no modality to prevent uterine fibrosis after curettage.…”