Akademik Veri Yönetim Sistemi
CYTOTHERAPY, sa.6, 2023 (SCI-Expanded)
Mesenchymal Stem/Stromal Cells
CLINICAL-GRADE HUMAN SYNOVIAL FLUID-DERIVED
MESENCHYMAL STEM CELLS FOR DEGENERATIVE MENISCUS
THERAPY
O. Uysal1,2, H. Avci1,2,3,4, S. Gunes Bagis1,2, T. Semerci Sevimli1,2,
C. Ozel1,2, B. Demir Cevizlidere1,2, M. N. Soykan1,2, S. G. Kara1,2,5,
E. Qomi Ekenel1,2, B. Altug Tasa1,2, I. Yilmaz Basaran1,2, E. Apaydin1,
A. Ghorbani1,2, T. Ertem1,2, F. Gakhiyeva1,2, H. Uysal6, V. Sahinturk7,
A. Eker Sariboyaci1,2
1Cellular Therapy and Stem Cell Production Application and Research
Centre, ESTEM, Eskisehir Osmangazi Universitesi, Eskisehir, Eskisehir,
Turkey; 2Department of Stem Cell, Institute of Health Sciences,
Eskisehir Osmangazi University, Eskisehir, Turkey; 3Department of
Metallurgical and Materials Engineering, Engineering and Architecture
Faculty, Eskisehir Osmangazi Universitesi, Eskisehir, Eskisehir, Turkey;
4Translational Medicine Application and Research Center (TATUM),
Eskisehir Osmangazi University, Eskisehir, Turkey; 5Department
of Emergency Medicine, Eskisehir City Hospital, Eskisehir, Turkey;
6Vocational School of Health Services, Orthopedic Prosthetics and
Orthotics Program, Eskisehir Osmangazi Universitesi, Eskisehir, Eskisehir,
Turkey; 7Department of Histology&Embryology, Medical Faculty,
Eskisehir Osmangazi Universitesi, Eskisehir, Eskisehir, Turkey
Keywords: Personalized treatment, mesenchymal stem cell, clinical
trial.
Background & Aim: When meniscal tissue is damaged, there is no
gold standard medication and/or surgical treatment that can regenerate
the damaged tissue. Currently, although the most effective
treatment approach is the surgical method-partial meniscectomy, it
provides only symptomatic improvement. The aim of this study is
to develop the stem cell treatment protocol in addition/alternative
to the surgical method adapt it to the clinical practices, suitable for
use in human treatment. For this purpose, all steps of the production
process as a Good Manufacturing Practices (GMP)-grade cellular therapy
product from the collection of the synovial fluid sample from the
patient until the release of the final product; the standard operation
procedure of the production was prepared according to the legal regulations.
Methods, Results & Conclusion: Therefore, firstly mesenchymal
stem cells were isolated from human synovial fluid by xeno-free enzymatic
separation under GMP protocols (ESOGÜ, Clinical Research
Ethics Committee approval, 11/04/2019-20). hSF-MSCs were cultured
until the third passage. Sterility, serology, quality control and stem
cell characterization tests were performed for use in human therapy.
The final product release for use in treatment was prepared in accordance
with the procedure. hSF-MSCs were characterized according to
the minimum standard criteria of the International Society for Cellular
Therapy (ISTC) guidelines. In addition, sterility, serology, endotoxin
and mycoplasma tests were also negative in accordance with
the criteria for release as the final product. Finally, the documentation
of all stages of the cell processing and manufacturing process of this
cellular therapy product has been completed in accordance with the
T.C. Ministry of Health, TITCK “GMP Guideline for Manufactories of
Medicinal Products for Human Use” and “Communiqué on the Licensing
of Human Tissue and Cell Products and the Centres Carrying Out
the Production, Import, Export, Storage and Distribution Activities
of These Products”. As a result, the production process of stem cell
therapy product, which has both regenerative and anti-inflammatory
activity in the treatment of meniscal damage and complies with
legal and ethical regulations, has been made ready for licensing. Acknowledgements:
This study was supported by grants from the Scientific
and Technical Research Council of Turkey (TUBITAK 20AG003;
20AG031; 118C538).