Evaluation of the quality and safety of cryopreserved human multipotent mesenchymal stromal cells derived from placenta for the clinical use

Cover Page


Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

The application of multipotent mesenchymal stromal cells (MMSC] in recent years is more widely evaluated in clinical trials. MMSC possess a number of unique features: the ability to support hematopoiesis, facilitating engraftment of HSC; immunomodulatory effects, including in regard to «graft versus host» reaction, and ability to differentiate into various cells types, that is defined their involvement in tissue and organ repair processes. The use of MMSC does not require antigenic compatibility control that leads to high potential accessibility of cell therapy. The most actively MMSC are evaluated in therapy of hematological, immunological, autoimmune, hereditary and other diseases. The aim of the study was to assess the quality and safety of cryopreserved placenta-derived MMSC prepared for clinical application. MMSC were obtained from 90 samples of placenta according to registered medical technology ФС №2010/374 от 13.10.2010. We evaluated the quality of placental MMSC by bacterial and viral control; determined the viability of cells with trypan blue and 7AAD; confirmed the immunophenotype specific for MMSC by flow cytometry. The biological safety of MMSC was analyzed by G-banding technique (15-20 metaphase chromosomes]. 72 samples of placenta-derived MMSC (193 doses] were prepared and used with HSC transplantation to 22 patients (42 MMSC doses] for optimization of HSC engraftment, prevention, control and treatment of «graft versus host» disease, liver regeneration. MMSC transfusion was performed at a dose of 2mln/kg. The results showed that allogeneic placenta-derived MMSC harvested in compliance with strict quality control were safe for clinical use and offered several significant advantages: no special invasive procedure for their tissue source explantation, high proliferative index on the 4th passage of cultivation, which allowed getting the required amount of cells for maximal therapeutic effect.

About the authors

T. A Astrelina

Stem Cell Bank of the Moscow Department of Health, Mosow

A. E Gomzyakov

Stem Cell Bank of the Moscow Department of Health, Mosow

I. V Kobzeva

Stem Cell Bank of the Moscow Department of Health, Mosow

E. E Karpova

Stem Cell Bank of the Moscow Department of Health, Mosow

A. Y Kruglova

Stem Cell Bank of the Moscow Department of Health, Mosow

E. V Scorobogatova

D. Rogachev Federal Research Center of Pediatric Hematology, Oncology and Immunology, Moscow

D. N Balashov

Central Research Institute of Gastroenterology, Moscow

O. V Knyazev

Central Research Institute of Gastroenterology, Moscow

M. V Yakovleva

Stem Cell Bank of the Moscow Department of Health, Mosow

References

  1. Pittenger M.F., Mackay A.M., Beck S.C. et al. Multilineage potential of adult human mesenchymal stem cells. Science 1999; 284: 143-7.
  2. Bourin P., Sensebe L., Planat-Bechard V. et al. Culture and use of mesenchymal stem cells in phase I and II clinical trials. Stem cells international 2010; 2: 1-8.
  3. Battiwalla M., Hematti P. Mesenchymal stem cells in hematopoietic stem cell transplantation. Cytotherapy 2009; 11(5): 503-15.
  4. Dominici M., Le Blanc K., Mueller I. et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 2006; 8(4): 315-7.
  5. Rebeca S.Y. Wong Mesenchymal stem cells: angels or demons? Journal of biomedicine and biotechnology 2011; 2: 1-9.
  6. Le Blanc K., Frassoni F., Ball L. et al. Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet 2008; 371(9624): 1579-86.
  7. Le Blanc K., Rasmusson I., Sundberg B. et al. Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet 2004; 363(9419): 1439-41.
  8. Lazarus H.M., Koc O.N., Devine S.M. et al. Cotransplantation of HLA-identical sibling culture-expanded mesenchymal stem cells and hematopoietic stem cells in hematologic malignancy patients. Biol Blood Marrow Transplant. 2005; 11(5): 389-98.
  9. Kebriaei P., Robinson S. Treatment of graft-versus-host-disease with mesenchymal stromal cells. Cytotherapy 2011; 13(3): 262-8.
  10. Aldinucci A., Rizzetto L., Pieri L. et.al. Inhibition of immune synapse by altered dendritic cell actin distribution: a new pathway of mesenchymal stem cell immune regulation. J. Immunol. 2010; 185(9): 5102-10.
  11. Григорян А.С. Трансплантация мультипотентных мезенхимальных стволовых клеток для лечения реакции «трансплантант против хозяина». Клеточная трансплантология и тканевая инженерия 2006; 3 (5): 31-2.
  12. Ringden O., Uzunel M., Rasmusson I. et.al. Mesenchymal stem cells for treatment of therapy-resistant graft-versus-host disease. Transplantation 2006; 81(10): 1390-7.
  13. Zhu F., Guo G.H., Chen W. et.al. Effect of bone marrow-derived mesenchymal stem cells transplantation on the inflammatory response and lung injury in rabbit with inhalation injury. Zhonghua Shao Shang Za Zhi. 2010; 26(5): 360-5.
  14. Петинати Н.А. Профилактика реакции трансплантат против хозяина у больных гемобластозами после трансплантации аллоген-ных гемопоэтических стволовых клеток с помощью мультипотентных мезенхимальных стромальных клеток донора. [ди^ертация] Москва: Гематологичекий научный центр; 2013 г.
  15. Jorgensen C. Mesenchymal stem cells in arthritis: role of bone marrow microenvironment. Arthritis Res. Ther. 2010; 12(4): 135.15.
  16. Han Z., Jing Y., Zhang S. et al. The role of immunosuppression of mesenchymal stem cells in tissue repair and tumor growth. Cell & Bioscience 2012; 2: 8.
  17. Яковлева М.В., Астрелина Т.А., Осипова Е.Ю. и др. Экспансия ex vivo мезенхимальных стволовых клеток. Медицинская технология от 13.10.2010; ФС №2010/374.
  18. Буяновская О.А. Частота анеуплоидии в культурах мезенхимных стволовых клеток человека. [ди^ертация] Москва: Российской академии медицинских наук Медико-генетический научный центр РАМН; 2013 г.

Supplementary files

Supplementary Files
Action
1. JATS XML

Copyright (c) 2013 Eco-Vector



СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: 

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies