0000000000421512
AUTHOR
Hannes Campo
Bioengineering strategies of the uterus towards improving current investigative models and female reproductive health
In this thesis, we intended to develop tissue-engineering approaches based on decellularized (DC) uterine tissues obtained from whole organs to improve several aspects within reproductive medicine. We hypothesized that that the decellularization of whole uteri from different species has not only the potential to, one day, create tissue-engineered, transplantable organs but that the DC endometrial fraction can also be processed further into thin sections, ECM hydrogels and coatings that can be used as a biocompatible tissue-specific substrate for cell and embryo culture. Moreover, we intended to corroborate if the differences in the cyclically and drastically changing endometrium are transla…
Stem cell paracrine actions in tissue regeneration and its potential therapeutic effect in human endometrium: a retrospective study.
Objective: Determining genetic and paracrine mechanisms behind endometrial regeneration in Asherman's Syndrome and Endometrial Atrophy (AS/EA) patients after autologous CD133+ bone marrow-derived stem cells (CD133+BMDSCs) transplantation. Design: Retrospective study using human endometrial biopsies and mouse models. Setting: Fundación-IVI, IIS-La Fe, Valencia, Spain. Samples: Endometrial biopsies collected before and after CD133+BMDSCs therapy, from 8 women with AS/EA (NCT02144987). And uterus from 5 mice, with only left horns receiving CD133+BMDSCs therapy. Methods: In human samples, hematoxylin and eosin (H&E) staining, RNA arrays, PCR validation and neutrophil elastase (NE) immunohistoch…
Improved Models of Human Endometrial Organoids Based on Hydrogels from Decellularized Endometrium
Organoids are three-dimensional (3D) multicellular tissue models that mimic their corresponding in vivo tissue. Successful efforts have derived organoids from primary tissues such as intestine, liver, and pancreas. For human uterine endometrium, the recent generation of 3D structures from primary endometrial cells is inspiring new studies of this important tissue using precise preclinical models. To improve on these 3D models, we decellularized pig endometrium containing tissue-specific extracellular matrix and generated a hydrogel (EndoECM). Next, we derived three lines of human endometrial organoids and cultured them in optimal and suboptimal culture expansion media with or without EndoEC…
A Natural Xenogeneic Endometrial Extracellular Matrix Hydrogel Toward Improving Current Human in vitro Models and Future in vivo Applications
Decellularization techniques support the creation of biocompatible extracellular matrix hydrogels, providing tissue-specific environments for both in vitro cell culture and in vivo tissue regeneration. We obtained endometrium derived from porcine decellularized uteri to create endometrial extracellular matrix (EndoECM) hydrogels. After decellularization and detergent removal, we investigated the physicochemical features of the EndoECM, including gelation kinetics, ultrastructure, and proteomic profile. The matrisome showed conservation of structural and tissue-specific components with low amounts of immunoreactive molecules. EndoECM supported in vitro culture of human endometrial cells in t…
Comparison of different sources of platelet-rich plasma as treatment option for infertility-causing endometrial pathologies
Objective To study the effect of human plasma from different sources, namely, umbilical cord blood and adult blood platelet-rich plasma (PRP), on the regeneration of endometrial damage. Design Composition analysis, in vitro approaches, and a preclinical murine model using plasma to promote endometrial regeneration. Setting Hospital and university laboratories. Patient(s)/Animal(s) Adult plasma from four Asherman syndrome/endometrial atrophy patients and one fertile woman, commercial umbilical cord plasma, and uterine-damaged NOD/SCID mice model were used. Intervention(s) Endometrial stromal cells from primary culture and an endometrial stem cell line were cultured in vitro, and uterine-dama…