Evaluation of the impact of customized serum-free culture medium on the production of clinical-grade human umbilical cord mesenchymal stem cells: insights for future clinical applications.


Journal

Stem cell research & therapy
ISSN: 1757-6512
Titre abrégé: Stem Cell Res Ther
Pays: England
ID NLM: 101527581

Informations de publication

Date de publication:
27 Sep 2024
Historique:
received: 26 06 2024
accepted: 18 09 2024
medline: 28 9 2024
pubmed: 28 9 2024
entrez: 28 9 2024
Statut: epublish

Résumé

The selection of suitable culture medium is critical for achieving good clinical outcomes in cell therapy. To support the commercial application of stem cell therapy, customized culture media not only need to promote stem cell proliferation, but also need to save costs and meet industrial requirements for inter-batch consistency, efficacy, and biosafety. In this study, we developed a series of serum-free media (SFM) and elucidated the effects between different SFM, as well as between SFM and serum-containing meida (SCM), on human umbilical cord mesenchymal stem cells (hUC-MSCs) phenotype and function. We analyze and emphasize from the perspectives of clinical and commercial application why research on customized culture media is critical for the success of enterprises developing novel cellular therapeutics. We cultured hUC-MSCs with identical cell seeding densities in different formulations of SFM and SCM until passage 10 and examined the changes in cell phenotype and function. We analyzed the results with the commercial application requirments of the cellular therapy industry to assess the potential impact of customized culture media on inter-batch consistency, efficacy, stability, biosafety, and cost-effectiveness of industrial-scale cell production. hUC-MSCs cultured in SCM and SFM exhibit consistent cell morphology and surface molecule expression, but hUC-MSCs cultured in SFM demonstrate higher activity, superior proliferative capacity, and greater stability. Furthermore, hUC-MSCs cultured in different SFM exhibit differences in cell activity, proliferative capacity, senescent rate, and S/M ratio of cell cycle, while maintaining a normal karyotype after long-term in vitro cultivation. Moreover, we found that hUC-MSCs cultured in different media exhibit variations in paracrine capacity and in their support of hematopoietic stem cell (HSC) self-renewal. Considering the substantial funding and time required for cell-based drug development, our results underscore the importances of comprehensively optimizing the composition of medium for the specific disease prior to conducting clinical trials of cell-based therapies. The criteria for selecting culture medium should be based on the requirements of the target disease for cellular function. In addition, we provide a way to formulate different customized SFM, which is beneficial for the development of cell therapy industry.

Sections du résumé

BACKGROUND BACKGROUND
The selection of suitable culture medium is critical for achieving good clinical outcomes in cell therapy. To support the commercial application of stem cell therapy, customized culture media not only need to promote stem cell proliferation, but also need to save costs and meet industrial requirements for inter-batch consistency, efficacy, and biosafety. In this study, we developed a series of serum-free media (SFM) and elucidated the effects between different SFM, as well as between SFM and serum-containing meida (SCM), on human umbilical cord mesenchymal stem cells (hUC-MSCs) phenotype and function. We analyze and emphasize from the perspectives of clinical and commercial application why research on customized culture media is critical for the success of enterprises developing novel cellular therapeutics.
METHODS METHODS
We cultured hUC-MSCs with identical cell seeding densities in different formulations of SFM and SCM until passage 10 and examined the changes in cell phenotype and function. We analyzed the results with the commercial application requirments of the cellular therapy industry to assess the potential impact of customized culture media on inter-batch consistency, efficacy, stability, biosafety, and cost-effectiveness of industrial-scale cell production.
RESULTS RESULTS
hUC-MSCs cultured in SCM and SFM exhibit consistent cell morphology and surface molecule expression, but hUC-MSCs cultured in SFM demonstrate higher activity, superior proliferative capacity, and greater stability. Furthermore, hUC-MSCs cultured in different SFM exhibit differences in cell activity, proliferative capacity, senescent rate, and S/M ratio of cell cycle, while maintaining a normal karyotype after long-term in vitro cultivation. Moreover, we found that hUC-MSCs cultured in different media exhibit variations in paracrine capacity and in their support of hematopoietic stem cell (HSC) self-renewal.
CONCLUSION CONCLUSIONS
Considering the substantial funding and time required for cell-based drug development, our results underscore the importances of comprehensively optimizing the composition of medium for the specific disease prior to conducting clinical trials of cell-based therapies. The criteria for selecting culture medium should be based on the requirements of the target disease for cellular function. In addition, we provide a way to formulate different customized SFM, which is beneficial for the development of cell therapy industry.

Identifiants

pubmed: 39334391
doi: 10.1186/s13287-024-03949-0
pii: 10.1186/s13287-024-03949-0
doi:

Substances chimiques

Culture Media, Serum-Free 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

327

Subventions

Organisme : Science Assistance Project for Xinjiang
ID : 2024E02062
Organisme : National Natural Science Foundation of China
ID : 3239014
Organisme : National Natural Science Foundation of China
ID : 82304575
Organisme : Guangdong Provincial Basic and Applied Basic Research Fund
ID : 2022A1515110883
Organisme : Young Scientists Program of Guangzhou Laboratory
ID : No. QNPG24-09

Informations de copyright

© 2024. The Author(s).

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Auteurs

Lan Zhao (L)

Guangzhou National Laboratory, Guangzhou, 510005, People's Republic of China.

Beibei Ni (B)

Vaccine Research Institute, Cell-Gene Therapy Translational Medicine Research Centre, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, People's Republic of China.

Jinqing Li (J)

Division of Hematology and Oncology, Department of Geriatrics, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, People's Republic of China.

Rui Liu (R)

Guangzhou National Laboratory, Guangzhou, 510005, People's Republic of China.

Qi Zhang (Q)

Vaccine Research Institute, Cell-Gene Therapy Translational Medicine Research Centre, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, People's Republic of China.

Zhuangbin Zheng (Z)

Guangzhou National Laboratory, Guangzhou, 510005, People's Republic of China.

Wenjuan Yang (W)

Department of Hematology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, People's Republic of China. yangwj28@mail.sysu.edu.cn.

Wei Yu (W)

Guangzhou National Laboratory, Guangzhou, 510005, People's Republic of China. yu_wei@gzlab.ac.cn.

Lijun Bi (L)

Guangzhou National Laboratory, Guangzhou, 510005, People's Republic of China. bi_lijun@gzlab.ac.cn.

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