Open AccessEffect of conditioned medium of umbilical cord-derived mesenchymal stem cells as a culture medium for human granulosa cells: An experimental study
Author(s) -
Kanadi Sumapraja,
Andon Hestiantoro,
Isabella Kurnia Liem,
Arief Boediono,
Teuku Z Jacoeb
Publication year - 2022
Publication title -
international journal of reproductive biomedicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.445
H-Index - 29
eISSN - 2476-4108
pISSN - 2476-3772
DOI - 10.18502/ijrm.v19i12.10054
Subject(s) - survivin , mesenchymal stem cell , paracrine signalling , apoptosis , andrology , umbilical cord , stem cell , fetal bovine serum , insulin like growth factor , growth factor , chemistry , in vitro , biology , microbiology and biotechnology , immunology , medicine , receptor , biochemistry
Background: The umbilical cord-derived mesenchymal stem cells conditioned medium (UC-MSCs-CM) produces secretomes with anti-apoptotic properties, and has the potential to prevent apoptosis of granulosa cells (GC) during controlled ovarian hyperstimulation.
Objective: To observe the effect of UC-MSCs-CM on the interaction between pro- and anti-apoptotic proteins and the influence of growth differentiation factor 9 (GDF9) production in GC.
Materials and Methods: UC-MSCs-CM was collected from umbilical cord stem cell culture on passage 4. GC from 23 women who underwent in vitro fertilization were cultured and exposed to UC-MSCs-CM for 24 hr. Then RNA of the GC was extracted and the mRNA expression of BCL-2 associated X (BAX), survivin and GDF9 were analysed using quantitative real-time PCR. The spent culture media of the GC were collected for measurement of insulin growth factor 1 using ELISA.
Results: The expression of BAX was significantly different after UC-MSCs-CM exposure (4.09E-7 vs. 3.74E-7, p = 0.02). No significant changes occurred in survivin, BAX/survivin ratio, and GDF9 expression after UC-MSCs-CM exposure (p > 0.05). The IGF-1 level of the CM was significantly higher after the CM was used as a culture medium for GC (2.28 vs. 3.07 ± 1.72, p ≤ 0.001). A significant positive correlation was found between survivin and GDF9 (r = 0.966, p ≤ 0.001).
Conclusion: IGF-1 produced by UC-MSCs-CM can work in paracrine fashion through the IGF receptor, which can inhibit BAX and maintain GDF9 production. Moreover, under the influence of UC-MSCs-CM, GC are also capable of producing IGF-1, which can impact GC through autocrine processes.
Key words: Conditioned medium, BAX, Survivin, GDF9, IGF-1.