Human CD133(+) bone marrow-derived stem cells promote endometrial proliferation in a murine model of Asherman syndrome

Abstract

Objective: To investigate the engraftment and proliferation of superparamagnetic iron oxide nanoparticles (SPIOs)-labeled human CD133(+) bone marrow-derived stem cells (BMDSCs) in an animal model of Asherman syndrome (AS).

Design: Prospective experimental animal study.

Setting: University research laboratories.

Animal(s): Nonobese diabetic mice (strain code 394; NOD.CB17- Prkdc(scid)/NcrCrl) in which AS was induced according to a published protocol.

Intervention(s): Human CD133(+) BMDSCs were obtained from patients undergoing autologous cell therapy in refractory AS and endometrial atrophy, labeled with SPIOs and injected either intrauterinely (n = 5) or systemically through the tail vein (n = 5) in the animal model.

Main outcome measure(s): Accumulation of collagen and glycosaminoglycan deposits detected by trichrome staining. Percentage and localization of engrafted human SPIOs-labeled CD133(+) BMDSCs by Prussian blue staining. Cell proliferation assay using Ki67 and reverse transcriptase-polymerase chain reaction (PCR) for specific paracrine factors.

Result(s): The induction of the AS in the murine model was demonstrated by the accumulation of collagen and glycosaminoglycan deposits in the damaged horns by trichrome staining. Human SPIOs labeled CD133(+) BMDSCs homing represents 0.59% and 0.65% of total number of cells present in the horns after intrauterine or tail vein injections, respectively. Engrafted cells were localized around endometrial blood vessels, inducing proliferation in surrounding cells based on Ki67 and regulation of the paracrine factors thrombospondin 1 and insulin-like growth factor 1.

Conclusion(s): The injection of human SPIOs labeled CD133(+) BMDSCs in a murine model of AS confirms that these cells engraft around endometrial vessels, inducing proliferation of surrounding cells through paracrine molecules such as thrombospondin 1 and insulin-like growth factor 1.

Clinical trial registration number: NCT02144987.

Keywords: Asherman syndrome; CD133(+)cells; bone marrow-derived stem cells (BMDSCs); superparamagnetic iron oxide nanoparticles (SPIOs).