Influence of conditioned media from glial cell cultures on contractility of uterine in rats of different ages
DOI:
https://doi.org/10.18370/2309-4117.2022.63.85-90Keywords:
contractile activity, uterus, conditioned media, neurotrophic factors, glial cell culture, cryopreservationAbstract
Background. The physiological regulation of the uterine contractile activity changes with age, which leads to an increased number of prolonged labor and emergency caesarean sections in women giving birth at the age of 35+. One of the modern approaches to correct the function of the reproductive system is the use of from cell cultures. CM from glial cell culture contains neurotrophic factors that play an important role in maintaining the contractile function of the uterus. Current cell culture technologies include cryopreservation.
Objective: to research experimentally the effect of CM obtained from intact and cryopreserved cultures of glial cells on the contractile activity of the uterus in rats of different reproductive ages.
Materials and methods. The monolayer cell culture was obtained from the dorsal root ganglia of neonatal piglets and cryopreserved in the presence of cryoprotectant dimethyl sulfoxide. CM from native and cryopreserved cultures were collected for 28 days, after which fractions with a molecular weight of < 30 kDa were obtained from them by ultrafiltration. Rats at the age of 6 and 14 months, which corresponds to reproductive age and late reproductive age (LRA), were intraperitoneally injected with 0.2 ml of media from intact (ICM) or cryopreserved (CCM) cultures for 9 days. On the 30th – 32nd day after the end of the administration of CM animals were slaughtered and the uterine contractile activity was determined by the organ bath method, the relative area of myometrium and density of myocytes by histological method, the average area of labeling with specific antibodies to smooth muscle actin by immunohistochemical method. The statistical significance of differences was assessed by the Mann–Whitney test.
Results. It was found that spontaneous, OT-, and KCl-induced tension of isometric contraction of the uterus in intact LRA rats decreased by 19, 20, and 14%, respectively, compared with intact reproductive aged animals. After the introduction of ICM and CCM in LRA animals, normalization of isometric contraction parameters was observed. This effect was realized against the background of an increase in the area of the myometrium, the density of myocytes, and actin expression.
Conclusions. Intra-abdominal administration of CM from glial cell culture increases the uterine contractile activity in LRA rats. This effect is realized by increasing the relative area of the myometrium, the density
of myocytes, and the area of expression of smooth muscle actin. The effect of media from intact and cryopreserved cultures on the contractile activity of the uterus was similar, which makes it possible to use low-temperature culture storage technologies to obtain CM without losing its biological effect.
References
- Korb, D., Goffinet, F., Seco, A., et al. “Risk of severe maternal morbidity associated with cesarean delivery and the role of maternal age: a population-based propensity score analysis.” CMAJ 191.13 (2019): E352–E360. DOI: org/10.1503/cmaj.181067
- Vandekerckhove, M., Guignard, M., Civadier, M., et al. “Impact of maternal age on obstetric and neonatal morbidity: a retrospective cohort study.” BMC Pregnancy Childbirth 21.1 (2021): 732. DOI: 10.1186/s12884-021-04177-7
- Bellien, C. “The best age for pregnancy and undue pressures.” J Family Reprod Health 10.3 (2016): 104–7. Available from: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5241353/].
- Seawright, J.W., Sreenivasappa, H., Gibbs, H.C., et al. “Vascular smooth muscle contractile function declines with age in skeletal muscle feed arteries.” Front Physiol 9 (2018): 856–66. DOI: 10.3389/fphys.2018.00856
- Ranson, R.N., Saffrey, M.J. “Neurogenic mechanisms in bladder and bowel ageing.” Biogerontology 16.2 (2015): 265–84. DOI: 10.1007/s10522-015-9554-3
- Elmes, M., Szyszka, A., Pauliat, C., et al. “Maternal age effects on myometrial expression of contractile proteins, uterine gene expression, and contractile activity during labor in the rat.” Physiol Rep 3.4 (2015): e12305. DOI: 10.14814/phy2.12305
- Abcejo, A.J., Sathish, V., Smelter, D.F., et al. “Brain-derived neurotrophic factor enhances calcium regulatory mechanisms in human airway smooth muscle.” PLoS ONE 7.8 (2012): e44343. DOI: 10.1371/journal.pone.0044343
- Aravamudan, B., Thompson, M., Pabelick, C., Prakash, Y.S. “Brain-derived neurotrophic factor induces proliferation of human airway smooth muscle cells.” J Cell Mol Med 16.4 (2012): 812–23. DOI: 10.1111/j.1582-4934.2011.01356.x
- Barcena de Arellano, M.L., Oldeweme, J., Arnold, J., et al. “Remodeling of estrogen-dependent sympathetic nerve fibers seems to be disturbed in adenomyosis.” Fertil Steril 100.3 (2013): 801–9. DOI: 10.1016/j.fertnstert.2013.05.013
- Brauer, M.M., Smith, P.G. “Estrogen and female reproductive tract innervation: cellular and molecular mechanisms of autonomic neuroplasticity.” Auton Neurosci 187 (2015): 1–17. DOI: 10.1016/j.autneu.2014.11.009
- Uvnäs-Moberg, K., Ekström-Bergström, A., Berg, M., et al. “Maternal plasma levels of oxytocin during physiological childbirth – a systematic review with implications for uterine contractions and central actions of oxytocin.” BMC Pregnancy Childbirth 19.1 (2019): 285. DOI: 10.1186/s12884-019-2365-9
- Ding, C., Zou, Q., Wang, F., et al. “Human amniotic mesenchymal stem cells improve ovarian function in natural aging through secreting hepatocyte growth factor and epidermal growth factor.” Stem Cell Res Ther 9 (2018): 55. DOI: 10.1186/s13287-018-0781-9
- Prokopyuk, V.Y., Karpenko, V.G., Shevchenko, M.V., et al. “Experience in clinical application of cryopreserved placental derivatives: cells, tissue, membranes, extract, and cord blood serum.” Innov Biosyst Bioeng 4.3 (2020): 168–76. DOI: 10.20535/ibb.2020.4.3.215215
- Teixeira, F.G., Carvalho, M.M., Sousa, N., et al. “Mesenchymal stem cells secretome: a new paradigm for central nervous system regeneration?” Cell Mol Life Sci 70.20 (2013): 3871–82. DOI: 10.1007/s00018-013-1290-8
- Vizoso, F.J., Eiro, N., Cid, S., et al. “Mesenchymal stem cell secretome: Toward cell-free therapeutic strategies in regenerative medicine.” Int J Mol Sci 18.9 (2017): 1852. DOI: 10.3390/ijms18091852
- Moshy, S.E., Radwan, I.A., Rady, D., et al. “Dental stem cell-derived secretome/conditioned medium: The future for regenerative therapeutic applications.” Stem Cells Int 2020 (2020): 7593402. DOI: 10.1155/2020/7593402
- Gwam, C., Mohammed, N., Ma, X. “Stem cell secretome, regeneration, and clinical translation: a narrative review.” Ann Transl Med 9.1 (2021): 70. DOI: 10.21037/atm-20-5030
- Gunawardena, T.N.A., Rahman, M.T., Abdullah, B.J.J., et al. “Conditioned media derived from mesenchymal stem cell cultures: The next generation for regenerative medicine.” J Tissue Eng Regen Med 13.4 (2019): 569–86. DOI: 10.1002/term.2806
- Abdel-Maguid, E.M., Awad, S.M., Hassan, Y.S., et al. “Efficacy of stem cell-conditioned medium vs platelet-rich plasma as an adjuvant to ablative fractional CO2 laser resurfacing for atrophic post-acne scars: a split-face clinical trial.” J Dermatolog Treat 32.2 (2021): 242–9. DOI: 10.1080/09546634.2019.1630701
- Katagiri, W., Watanabe, J., Toyama, N., et al. “Clinical study of bone regeneration by conditioned medium from mesenchymal stem cells after maxillary sinus floor.” Elevation Implant Dent 26.4 (2017): 607–12. DOI: 10.1097/ID.0000000000000618
- Prakoeswa, C.R.S., Natallya, F.R., Harnindya, D., et al. “The efficacy of topical human amniotic membrane-mesenchymal stem cell-conditioned medium (hAMMSC-CM) and a mixture of topical hAMMSC-CM + vitamin C and hAMMSC-CM + vitamin E on chronic plantar ulcers in leprosy: a randomized control trial.” J Dermatolog Treat 29.8 (2018): 835–40. DOI: 10.1080/09546634.2018.1467541
- Lee, Y.I., Kim, J., Kim, J., et al. “The effect of conditioned media from human adipocyte-derived mesenchymal stem cells on androgenetic alopecia after nonablative fractional laser treatment.” Dermatol Surg 46.12 (2020): 1698–1704. DOI: 10.1097/DSS.0000000000002518
- Walker, M.J., Xu, X.M. “History of glial cell line-derived neurotrophic factor (GDNF) and its use for spinal cord injury repair.” Brain Sci 8.6 (2018): 109. DOI: 10.3390/brainsci8060109
- Ruiz, C., Casarejos, M.J., Gomez, A., et al. “Protection by glia-conditioned medium in a cell model of Huntington disease.” PLoS Curr 4 (2012): e4fbca54a2028b. DOI: 10.1371/4fbca54a2028b
- Sengupta, P. “The laboratory rat: relating its age with human’s.” Int J Prev Med 4.6 (2013): 624–30. PMID: 23930179; PMCID: PMC3733029.
- Ali, S.G., Moiseieva, N.M., Bozhok, G.A. “Cryopreservation of cell culture derived from dorsal root ganglia of neonatal pigs.” Probl Cryobiol Cryomed 30.2 (2020): 158–68. DOI: 10.15407/cryo30.02.158
- Nesteruk, H.V., Ustichenko, V.D., Alabedalkarim, N.М., et al. “Impact of dorsal root ganglia cryoextract on histological features and contractility of uterus in differently aged rats.” Probl Cryobiol Cryomed 31.3 (2021): 258–67. DOI: 10.15407/cryo31.03.258
- Arrowsmith, S., Robinson, H., Noble, K., et al. “What do we know about what happens to myometrial function as women age?” J Muscle Res Cell Motil 33.3–4 (2012): 209–17. DOI: 10.1007/s10974-012-9300-2
- Ghosh, D., Syed, A.U., Prada, M.P., et al. “Calcium channels in vascular smooth muscle.” Adv Pharmacol 78 (2017): 49–87. DOI: 10.1016/bs.apha.2016.08.002
- Ferreira, J.J., Butler, A., Stewart, R., et al. “Oxytocin can regulate myometrial smooth muscle excitability by inhibiting the Na+-activated K+ channel Slo2.1.” J Physiol 597.1 (2019): 137–49. DOI: 10.1113/JP276806
- Kwapiszewska, G., Chwalek, K., Marsh, L.M., et al. “BDNF/TrkB signaling augments smooth muscle cell proliferation in pulmonary hypertension.” Am J Pathol 181.6 (2012): 2018–29. DOI: 10.1016/j.ajpath.2012.08.028
- Zierold, S., Buschmann, K., Gachkar, S., et al. “Brain-derived neurotrophic factor expression and signaling in different perivascular adipose tissue depots of patients with coronary artery disease.” J Am Heart Assoc 10.6 (2021): e018322. DOI: 10.1161/JAHA.120.018322
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2022 Г.В. Нестерук, Н.М. Алабедалькарім, Н.А. Комаромі, Н.О. Ткаченко, О.С. Проценко, Є.І. Легач
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.