N 1 (186) 2024 р. P. 35–41

ANALGESIC POTENTIAL OF CRYOEXTRACTS OF BIOLOGICAL TISSUES AND CONDITIONED MEDIA OF MESENCHYMAL STEM CELLS IN THE TREATMENT OF EXPERIMENTAL AUTOIMMUNE ARTHRITIS

F. V. Hladkykh, T. I. Liadova

N. Karazin Kharkiv National University, Kharkiv, Ukraine
State Organization “Grigoriev Institute for Medical Radiology and Oncology of the National Academy of Medical Sciences of Ukraine”, Kharkiv, Ukraine

DOI 10.32782/2226-2008-2024-1-6

Background. Treating pain syndrome remains the focus of clinicians’ attention, and developing new treatment methods is an urgent task of modern medicine. Particular attention is drawn to the results of recent studies on the use of cell-free cryopreserved biological agents to optimize anti-inflammatory and analgesic therapy for a number of autoimmune diseases.

Objective – to characterize the analgesic activity of cryoextract of placenta (CEP), cryoextract of spleen, and conditioned medium of mesenchymal stem cells in the model of autoimmune arthritis (АА) in rats.

Methods. Experimental studies were conducted on 42 male rats weighing 200–220 g. AA was modeled by sub-plantar administration of complete Freund’s adjuvant. AA treatment was carried out from 14 to 28 days. On “0” (initial indicators), 14 and 28 days of the experiment, pain sensitivity was assessed (electrical impulse irritation and mechanical irritation according to Randall-Selitto).

Results. The conducted study showed that on the 14th day of the experiment in rats with simulated AA, a statistically significant (p<0.009) decrease by 2 times in the threshold of pain sensitivity with mechanical irritation according to Randall-Selitto was observed relative to the initial indicators. Evaluation of the effect of administration of biological agents to rats with AA demonstrated the ability of the studied drugs to reduce the threshold of pain sensitivity from the action of a mechanical stimulus, which indicates the modulation of the peripheral component of nociception. Against the background of the introduction of СEP to rats with AA, a statistically significant (p=0.01) increase in threshold of pain sensitivity from an electrical impulse stimulus was noted by 44.7%.

Conclusions. At the spinal level of nociception, cryoextract of placenta and conditioned medium of mesenchymal stem cells showed comparable analgesic activity, which was 43.1% and 42.7%, respectively. At the supraspinal level of nociception, the most pronounced analgesic activity was found in the conditioned medium of mesenchymal stem cells, which was 54.8%, that is only 18.8% lower (p=0.049) than the indicators of rats administered diclofenac sodium.

Key words: cell-free cryopreserved biological agents, autoimmune diseases, spleen cryoextract, placenta cryoextract, mesenchymal stem cell conditioned medium.

REFERENCES

  1. Radu AF, Bungau SG. Management of Rheumatoid Arthritis: An Overview. Cells. 2021; 10(11):2857. https://doi.org/10.3390/ cells10112857.
  2. Hladkykh FV. Current understanding of the immunological basis of rheumatoid arthritis: from post-translational modification of proteins to the use of disease-modifying antirheumatic drugs. Eastern Ukrainian medical journal. 2023; 11(4):326–336. https://doi.org/10.21272/eumj.2023;11(4):326-336.
  3. Hladkykh FV. Cell-free biologics: focus on mesenchymal stem cell conditioned media. Odesa Medical Journal. 2023; 4(185):75–82. https://doi.org/10.32782/2226-2008-2023-4-15.
  4. Hladkykh FV. Mesenchymal stem cells: exosomes and conditioned media as innovative strategies in the treatment of patients with autoimmune diseases. Clinical and Preventive Medicine. 2023(6):121–130. https://doi.org/10.31612/2616-4868.6.202 3.15.
  5. Hladkykh FV. Anti-inflammatory properties of diclofenac sodium on background of its combined use with cryopreserved placenta extract in experiment. Problems of Cryobiology and Cryomedicine. 2021; 31(4):364–367. https://doi.org/10.15407/ cryo31.04.364.
  6. He L, He T, Xing J, Zhou Q, Fan L, Liu C, Chen Y, Wu D, Tian Z, Liu B, Rong L. Bone marrow mesenchymal stem cell-derived exosomes protect cartilage damage and relieve knee osteoarthritis pain in a rat model of osteoarthritis. Stem Cell Res Ther. 2020; 11(1):276. https://doi.org/10.1186/s13287-020-01781-w.
  7. Stefanov OV, ed. Preclinical studies of medicinal products: methodical recommendations. Kyiv: Avicenna; 2001. 527 p.
  8. Hladkykh FV. Nonsteroidal anti-inflammatory drugs: therapeutic and undesirable effects, ways of their optimization. Vinnytsia: Tvory; 2022. 216 p. https://doi.org/10.46879/2022.1.
  9. Shepitko VI. Structural and functional indicators of the cryopreserved liver and the effect of its transplantation on the morphofunctional state of a number of internal organs: dissertation. Doctor of Medicine: special. 14.01.35 “Cryomedicine”, Kharkiv, 2004. 326 p. https://nrat.ukrintei.ua/searchdoc/0504U000610/.
  10. Bespalova IG. Peptide composition and biological action of extracts of cryopreserved pig spleen fragments and piglet skin: thesis. biol. n.: spec. 03.00.19 “Cryobiology”, Kharkiv, 2016. 162 p. Available from: https://nrat.ukrintei.ua/ searchdoc/0416U004539/.
  11. Globa VYu. Use of cryopreserved cell cultures and neurotrophic factors in experimental infravesical obstruction. Thesis in specialty 222 “Medicine”, Kharkiv, 2021. 156 p. Available from: https://nrat.ukrintei.ua/searchdoc/0821U100913/.
  12. Ben-Bassat J, Peretz E, Sulman FG. Analgesimetry and ranking of analgesic drugs by the receptacle method. Archives Internationales de Pharmacodynamie et de Therapie. 1959; 122:434–447.
  13. Randall L, Selitto J. A method for measurement of analgesic activity on inflammed tissue. Archives of International Pharmacodynamics. 1957; 111:409–419.
  14. Hatsura VV. Methods of primary pharmacological research of biologically active substances. M.: Medicine; 1974. 142 p.
  15. Galchenko SE, Shkodovska NY, Sandomirsky BP, Hryshchenko VI. Patent of Ukraine No. 64381. Method of obtaining extracts of xenogenic organs. Application No. 2003054649. Submitted on May 22, 2003; Publ. 16.02.2004. Bul. No. 2.
  16. Ye Z, Zhang M, Ding N, Gao P, Hei Y, Wang Y, Gao W, Ye Q. Antinociceptive effects of dezocine on complete Freund’s adjuvant-induced inflammatory pain in rats. Exp Ther Med. 2018; 15(6):5469–5474. https://doi.org/10.3892/etm.2018.6110.
  17. Kwok CHT, Learoyd AE, Canet-Pons J, Trang T, Fitzgerald M. Spinal interleukin-6 contributes to central sensitisation and persistent pain hypersensitivity in a model of juvenile idiopathic arthritis. Brain Behav Immun. 2020; 90:145–154. https://doi.org/10.1016/j.bbi.2020.08.004.
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