Document Type : Original Article(s)

Authors

• Dana Saipiyeva ¹
• Manarbek Askarov ¹
• Nazanin Jafari ²
• Rano Zhankina ³
• Paul R. Heath ⁴
• Larissa Kozina ⁵
• Alyona Boltanova ⁵
• Ardak Omarbekov ⁶
• Nurbek Ilyassov ⁷
• Turlybek Tuganbekov ⁶
• Nadiar M. Mussin ⁸
• Asset A. Kaliyev ⁸
• Yerlan Sultangereyev ⁸
• Farhad Rahmanifar ⁹
• Mahdi Mahdipour ^{10, 11}
• Shabnam Bakhshalizadeh ¹²
• Reza Shirazi ¹³
• Nader Tanideh ^{2, 14, 15}
• Amin Tamadon ¹⁶

¹ Cell Technologies, Transplantation and Research Department, National Scientific Medical Center, Astana, Kazakhstan

² PerciaVista R&D Co. Shiraz, Iran

³ Department of Urology and Andrology, Astana Medical University, Astana, Kazakhstan

⁴ Sheffield Institute for Translational Neuroscience (SITraN), Department of Neuroscience, University of Sheffield, 385 Glossop Road, Sheffield S10 2HQ, UK

⁵ Clinical and Diagnostic Laboratory, National Scientific Medical Center, Astana, Kazakhstan

⁶ Surgical Diseases, Angiosurgery and Plastic Surgery Department, Astana Medical University, Astana, Kazakhstan

⁷ Department of Surgery, National Scientific Medical Center, Astana, Kazakhstan

⁸ General Surgery, West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan

⁹ Department of Basic Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, Iran

¹⁰ Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

¹¹ Department of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran

¹² Reproductive Development, Murdoch Children’s Research Institute, Melbourne, Victoria, Australia

¹³ Department of Anatomy, School of Biomedical Sciences, Medicine and Health, UNSW Sydney, Sydney, Australia

¹⁴ Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

¹⁵ Department of Pharmacology, Medical School, Shiraz University of Medical Sciences, Shiraz, Iran

¹⁶ Department of Natural Sciences, West Kazakhstan Marat Ospanov Medical University, Maresyev St, Aktobe, Kazakhstan

Abstract

Background: Primary biliary cholangitis (PBC) is a condition affecting the liver and immune system. In this study, the impact of autologous bone marrow-derived mononuclear cell (BM-MNC) transplantation on PBC patients was investigated. 
Methods: Sixteen eligible PBC patients participated at the National Scientific Medical Center in Astana, Kazakhstan, between 2017 and 2022, and BM-MNCs were harvested from their anterior iliac crest. After isolating and cultivating the BM-MNCs, they were infused back into the patient’s peripheral veins. Changes in BM-MNC and peripheral blood mononuclear cell (PB-MNC) phenotypes were assessed before and after a 24-hour cultivation period and 72 hours post-transplantation. We monitored liver function parameters over 6-month intervals and conducted flow cytometry analysis to assess CD markers on BM-MNCs before and after cultivation and PB-MNCs before and after transplantation. Statistical analysis included the Friedman test for liver parameters and the Wilcoxon signed-rank test for BM-MNC and PB-MNC comparisons.
Results: Our findings revealed significant reductions in liver function tests after multiple transplantations. Flow cytometry analysis before and after a 24-hour culture and autologous BM-MNC infusion revealed the expansion of specific cell populations, with significant increases in CD3+, CD4+, CD16+, CD20+, CD25+, CD34+, CD105+, CD73+, СD117+, and CD34+populations, while CD4+25+, CD34+105+, and CD4+FOXP3+ populations decreased. Interestingly, a contradictory finding was observed with a decrease in bone marrow CD34+105+ cell lines (P=0.03) alongside an increase in peripheral CD34+105+ population (P=0.03).
Conclusion: In summary, our study shows that BM-MNC transplantation in PBC patients leads to changes in immune cell populations and liver function. These findings suggest potential therapeutic applications of BM-MNC transplantation in managing PBC and offer insights into the dynamics of immune cells associated with this treatment approach.

Keywords

• Primary biliary cholangitis
• Leukocytes, mononuclear
• Bone marrow
• Peripheral blood stem cells