Stem Cell Growth and Differentiation in Organ Culture: New Insights for Uterine Fibroid Treatment

Abstract

Organ culture allows for the understanding of normal and tumor cell biology, and tissues generally remain viable for 5–7 days. Strikingly, we determined that myometrial and MED12 mutant leiomyoma cells repopulated cell-depleted tissue slices after 20 days of culture. Using immunofluorescence and quantitative PCR of stem cell and undifferentiated cell markers, we observed clusters of CD49b+ cells in tumor slices. CD49b+ cells, however, were sparsely detected in the myometrial slices. Almost all LM cells strongly expressed Ki67, while only a few myometrial cells were stained for this proliferation marker. The CD73 marker was expressed only in tumor cells, whereas the mesenchymal stem cell receptor KIT was detected only in normal cells. HMGA2 and CD24 showed broader expression patterns and higher signal intensity in leiomyoma than in myometrial cells. In this study, we propose that activating CD49b+ stem cells in myometrium leads to asymmetrical division, giving rise to transit-amplifying KIT+ cells that differentiate to smooth muscle cells. On the contrary, activated leiomyoma CD49b+ cells symmetrically divide to form clusters of stem cells that divide and differentiate to smooth muscle cells without losing proliferation ability. In conclusion, normal and mutant stem cells can proliferate and differentiate in long-term organ culture, constituting a helpful platform for novel therapeutic discovery.

Analysis of risk factors for postoperative bleeding and recurrence after laparoscopic myomectomy in patients with uterine fibroids: a retrospective cohort study

“…Despite their high prevalence, up to 70% of fibroids are asymptomatic and thus do not require frequent follow-up or medical intervention ( 8 ). The differences in the sizes and locations of fibroids can lead to different clinical symptoms, with 15–30% of patients experiencing severe symptoms ( 18 ), such as abnormal uterine bleeding, dysmenorrhea, urinary frequency or constipation, sexual dysfunction, and infertility, which impair their physical and mental health ( 19 ). Although UFs are benign tumors, there is also a possibility of malignant transformation, and the malignancy rate of patients with UFs is about 0.5% in China and about 0.13–1.0% in foreign countries.…”

Gender Medicine and Pharmacology

“…Another work conducted by Salas and colleagues observed that myometrial and MED12 mutant leiomyoma cells repopulated cell-depleted tissue slices after 20 days of culture. They detected clusters of CD49b+ cells in tumor slices using immunofluorescence and quantitative PCR of stem cell and undifferentiated cell markers [50]. However, there were only a few CD49b+ cells found in the myometrial slices.…”