3D bioprinted endometrial stem cells on melt electrospun poly ε-caprolactone mesh for pelvic floor application promote anti-inflammatory responses in mice

Impact of Sustained Transforming Growth Factor-β Receptor Inhibition on Chromatin Accessibility and Gene Expression in Cultured Human Endometrial MSC

“…Preclinical animal studies showed that eMSC are a promising cell source for treatment of gynecological disorders, including pelvic organ prolapse ( Darzi et al, 2016 ; Gargett et al, 2019 ). For example, eMSC seeded or bio-printed onto meshes with biomechanical properties matching the human vagina (e.g., non-degradable polyamide/gelatin composite meshes) ( Ulrich et al, 2014 ; Emmerson et al, 2019 ), or on degradable nanofibers ( Mukherjee et al, 2019b ; Paul et al, 2019 ), promote angiogenesis, collagen deposition, and cellular infiltration into biomaterials when transplanted into rodent or ovine models. They also elicit an early inflammatory response, characterized first by influx of M1 macrophages, which then switch to the M2 wound healing phenotype ( Ulrich et al, 2014 ; Darzi et al, 2018 ).…”

Laparoscopy for the Treatment of Congenital Hernia: Use of Surgical Meshes and Mesenchymal Stem Cells in a Clinically Relevant Animal Model

“…First, there is a lack of uniformity regarding the use of animal models in preclinical trials (Vogels et al, 2017). Even the most recent studies that have investigated the use of stem cells on surgical meshes have been performed in vitro (Gao et al, 2014;Vozzi et al, 2017) or in small animal models, especially in mice (Darzi et al, 2018;Paul et al, 2019;Mukherjee et al, 2020), rats (Altman et al, 2010a;Altman et al, 2010b;Edwards et al, 2015;Iyyanki et al, 2015;Klinger et al, 2016;van Steenberghe et al, 2017;Hansen et al, 2020), and rabbits (Zhao et al, 2012;Cheng et al, 2017). Only a few preclinical studies have been performed in sheep (Gerullis et al, 2013;Gerullis et al, 2014).…”

“…Third, surgical meshes can be used to reinforce tissues in pelvic prolapses or hernias, but these two conditions are quite different. The most recent and relevant studies investigating the use of stem cells on surgical meshes are focused towards reinforcement of the pelvic floor (Emmerson et al, 2019;Paul et al, 2019;Mukherjee et al, 2020) rather than of the abdominal wall; however, it is necessary to consider the fundamental differences between the two pathological conditions in the evaluation of preclinical trials. Fourth, even though standardization and reproducibility are very important to obtain consistent results in research, the clinical setting is characterized by a huge variability in patients, with a variety of body masses and type, position, and size of hernias.…”

MSC-based therapy in female pelvic floor disorders

“…Adult human endometrium contains a small quantity of epithelial progenitors and MSCs, which may provide a readily available source of MSCs for cell-based therapies [43,44]. Recently, several studies combining eMSCs with new biomaterials gained good results in skin wound repair or abdominal hernia animal models [45,46], demonstrating eMSCs are candidate seeding cells for tissue engineered meshes in the treatment of POMoreover, the convenience of eMSCs acquisition (endometrial biopsies in an office-based procedure) and the discovery that eMSCs can be also isolated from post-menopausal endometrium [47] contribute to their potential clinical use for PFDs.…”

“…In recent years, there has been an increasing interest in applying eMSCs to tissue engineering therapy for pelvic floor repair [46,78,85] and the eMSCs have exhibited an excellent modulatory property to the extra cellular matrix remodeling and the inflammatory reactions, but the mechanism remains unclear. A study [86] characterized some of the immunomodulatory properties of eMSCs in vivo to understand the immunoregulatory mechanism of eMSCs on macrophages.…”