Umbilical Cord-Derived Mesenchymal Stem Cells Are Able to Use
bFGF Treatment and Represent a Superb Tool for
Immunosuppressive Clinical Applications

J 2020

Umbilical Cord-Derived Mesenchymal Stem Cells Are Able to Use bFGF Treatment and Represent a Superb Tool for Immunosuppressive Clinical Applications

TESAŘOVÁ, Lenka, Klára JAREŠOVÁ, Pavel ŠIMARA and Irena KOUTNÁ

Basic information

Original name

Umbilical Cord-Derived Mesenchymal Stem Cells Are Able to Use bFGF Treatment and Represent a Superb Tool for Immunosuppressive Clinical Applications

Authors

TESAŘOVÁ, Lenka (203 Czech Republic, guarantor, belonging to the institution), Klára JAREŠOVÁ (203 Czech Republic, belonging to the institution), Pavel ŠIMARA (203 Czech Republic, belonging to the institution) and Irena KOUTNÁ (203 Czech Republic, belonging to the institution)

Edition

International Journal of Molecular Sciences, Basel, Multidisciplinary Digital Publishing Institute, 2020, 1422-0067

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10608 Biochemistry and molecular biology

Country of publisher

Switzerland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 5.923

RIV identification code

RIV/00216224:14110/20:00116470

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.3390/ijms21155366

UT WoS

000567132000001

Keywords in English

mesenchymal stem cells; umbilical cord; advanced therapy medicinal product; immunosuppression

Abstract

V originále

Mesenchymal stem cells (MSCs) have become a promising tool in cellular therapy for restoring immune system haemostasis; however, the success of clinical trials has been impaired by the lack of standardized manufacturing processes. This study aims to determine the suitability of source tissues and culture media for the production of MSC-based advanced therapy medicinal products (ATMPs) and to define parameters to extend the set of release criteria. MSCs were isolated from umbilical cord (UC), bone marrow and lipoaspirate and expanded in three different culture media. MSC phenotype, proliferation capacity and immunosuppressive parameters were evaluated in normal MSCs compared to primed MSCs treated with cytokines mimicking an inflammatory environment. Compared to bone marrow and lipoaspirate, UC-derived MSCs (UC-MSCs) showed the highest proliferative capacity, which was further enhanced by media supplemented with bFGF, while the cells maintained their immunosuppressive characteristics. Moreover, UC-MSCs expanded in the bFGF-enriched medium were the least sensitive to undesirable priming-induced changes in the MSC phenotype. Surface markers and secreted factors were identified to reflect the cell response to inflammatory priming and to be variable among MSCs from different source tissues. This study demonstrates that UC is a favorable cell source for manufacturing MSC-based ATMPs for immunosuppressive applications. UC-MSCs are able to use the bFGF-enriched medium for higher cell yields without the impairment of immunosuppressive parameters and undesirable phenotype changes after inflammatory preconditioning of MSCs before transplantation. Additionally, immunosuppressive parameters were identified to help finding predictors of clinically efficient MSCs in the following clinical trials.

Links

LM2018128, research and development project

Name: Český národní uzel Evropské sítě infrastruktur klinického výzkumu (Acronym: CZECRIN)

Investor: Ministry of Education, Youth and Sports of the CR

Citovat

TESAŘOVÁ, Lenka, Klára JAREŠOVÁ, Pavel ŠIMARA and Irena KOUTNÁ. Umbilical Cord-Derived Mesenchymal Stem Cells Are Able to Use bFGF Treatment and Represent a Superb Tool for Immunosuppressive Clinical Applications. International Journal of Molecular Sciences. Basel: Multidisciplinary Digital Publishing Institute, 2020, vol. 21, No 15, p. 1-27. ISSN 1422-0067. Available from: https://dx.doi.org/10.3390/ijms21155366.

@article{1680205,
   author = {Tesařová, Lenka and Jarešová, Klára and Šimara, Pavel and Koutná, Irena},
   article_location = {Basel},
   article_number = {15},
   doi = {http://dx.doi.org/10.3390/ijms21155366},
   keywords = {mesenchymal stem cells; umbilical cord; advanced therapy medicinal product; immunosuppression},
   language = {eng},
   issn = {1422-0067},
   journal = {International Journal of Molecular Sciences},
   title = {Umbilical Cord-Derived Mesenchymal Stem Cells Are Able to Use bFGF Treatment and Represent a Superb Tool for Immunosuppressive Clinical Applications},
   url = {https://www.mdpi.com/1422-0067/21/15/5366},
   volume = {21},
   year = {2020}
}

TY  - JOUR
ID  - 1680205
AU  - Tesařová, Lenka - Jarešová, Klára - Šimara, Pavel - Koutná, Irena
PY  - 2020
TI  - Umbilical Cord-Derived Mesenchymal Stem Cells Are Able to Use bFGF Treatment and Represent a Superb Tool for Immunosuppressive Clinical Applications
JF  - International Journal of Molecular Sciences
VL  - 21
IS  - 15
SP  - 1-27
EP  - 1-27
PB  - Multidisciplinary Digital Publishing Institute
SN  - 14220067
KW  - mesenchymal stem cells
KW  - umbilical cord
KW  - advanced therapy medicinal product
KW  - immunosuppression
UR  - https://www.mdpi.com/1422-0067/21/15/5366
L2  - https://www.mdpi.com/1422-0067/21/15/5366
N2  - Mesenchymal stem cells (MSCs) have become a promising tool in cellular therapy for restoring immune system haemostasis; however, the success of clinical trials has been impaired by the lack of standardized manufacturing processes. This study aims to determine the suitability of source tissues and culture media for the production of MSC-based advanced therapy medicinal products (ATMPs) and to define parameters to extend the set of release criteria. MSCs were isolated from umbilical cord (UC), bone marrow and lipoaspirate and expanded in three different culture media. MSC phenotype, proliferation capacity and immunosuppressive parameters were evaluated in normal MSCs compared to primed MSCs treated with cytokines mimicking an inflammatory environment. Compared to bone marrow and lipoaspirate, UC-derived MSCs (UC-MSCs) showed the highest proliferative capacity, which was further enhanced by media supplemented with bFGF, while the cells maintained their immunosuppressive characteristics. Moreover, UC-MSCs expanded in the bFGF-enriched medium were the least sensitive to undesirable priming-induced changes in the MSC phenotype. Surface markers and secreted factors were identified to reflect the cell response to inflammatory priming and to be variable among MSCs from different source tissues. This study demonstrates that UC is a favorable cell source for manufacturing MSC-based ATMPs for immunosuppressive applications. UC-MSCs are able to use the bFGF-enriched medium for higher cell yields without the impairment of immunosuppressive parameters and undesirable phenotype changes after inflammatory preconditioning of MSCs before transplantation. Additionally, immunosuppressive parameters were identified to help finding predictors of clinically efficient MSCs in the following clinical trials.
ER  -

TESAŘOVÁ, Lenka, Klára JAREŠOVÁ, Pavel ŠIMARA and Irena KOUTNÁ. Umbilical Cord-Derived Mesenchymal Stem Cells Are Able to Use bFGF Treatment and Represent a Superb Tool for Immunosuppressive Clinical Applications. \textit{International Journal of Molecular Sciences}. Basel: Multidisciplinary Digital Publishing Institute, 2020, vol.~21, No~15, p.~1-27. ISSN~1422-0067. Available from: https://dx.doi.org/10.3390/ijms21155366.

Detailed Information on Publication Record