دورية أكاديمية
Strategies to enhance immunomodulatory properties and reduce heterogeneity in mesenchymal stromal cells during ex vivo expansion.
| العنوان: | Strategies to enhance immunomodulatory properties and reduce heterogeneity in mesenchymal stromal cells during ex vivo expansion. |
|---|---|
| المؤلفون: | Srinivasan A; Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore., Sathiyanathan P; Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore., Yin L; Bioprocessing Technology Institute, A*STAR, Singapore., Liu TM; Institute of Molecular and Cell Biology, A*STAR, Singapore., Lam A; Bioprocessing Technology Institute, A*STAR, Singapore., Ravikumar M; Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Institute of Molecular and Cell Biology, A*STAR, Singapore., Smith RAA; Institute of Molecular and Cell Biology, A*STAR, Singapore., Loh HP; Bioprocessing Technology Institute, A*STAR, Singapore., Zhang Y; Institute of Molecular and Cell Biology, A*STAR, Singapore., Ling L; Institute of Molecular and Cell Biology, A*STAR, Singapore., Ng SK; Bioprocessing Technology Institute, A*STAR, Singapore., Yang YS; Bioprocessing Technology Institute, A*STAR, Singapore., Lezhava A; Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore., Hui J; Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore., Oh S; Bioprocessing Technology Institute, A*STAR, Singapore. Electronic address: steve_oh@bti.a-star.edu.sg., Cool SM; Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Institute of Molecular and Cell Biology, A*STAR, Singapore. Electronic address: simon_cool@imcb.a-star.edu.sg. |
| المصدر: | Cytotherapy [Cytotherapy] 2022 May; Vol. 24 (5), pp. 456-472. Date of Electronic Publication: 2022 Feb 25. |
| نوع المنشور: | Journal Article; Review; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: England NLM ID: 100895309 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1477-2566 (Electronic) Linking ISSN: 14653249 NLM ISO Abbreviation: Cytotherapy Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2013- : London : Elsevier Original Publication: Oxford, England : ISIS Medical Media, c1999- |
| مواضيع طبية MeSH: | Hematopoietic Stem Cell Transplantation* , Mesenchymal Stem Cells*, Humans ; Immunomodulation |
| مستخلص: | Therapies using mesenchymal stromal cells (MSCs) to treat immune and inflammatory conditions are now at an exciting stage of development, with many MSC-based products progressing to phase II and III clinical trials. However, a major bottleneck in the clinical translation of allogeneic MSC therapies is the variable immunomodulatory properties of MSC products due to differences in their tissue source, donor heterogeneity and processes involved in manufacturing and banking. This variable functionality of MSC products likely contributes to the substantial inconsistency observed in the clinical outcomes of phase III trials of MSC therapies; several trials have failed to reach the primary efficacy endpoint. In this review, we discuss various strategies to consistently maintain or enhance the immunomodulatory potency of MSCs during ex vivo expansion, which will enable the manufacture of allogeneic MSC banks that have high potency and low variability. Biophysical and biochemical priming strategies, the use of culture additives such as heparan sulfates, and genetic modification can substantially enhance the immunomodulatory properties of MSCs during in vitro expansion. Furthermore, robust donor screening, the use of biomarkers to select for potent MSC subpopulations, and rigorous quality testing to improve the release criteria for MSC banks have the potential to reduce batch-to-batch heterogeneity and enhance the clinical efficacy of the final MSC product. Machine learning approaches to develop predictive models of individual patient response can enable personalized therapies and potentially establish correlations between in vitro potency measurements and clinical outcomes in human trials. Competing Interests: Competing Interests Statement The authors have no competing interests to declare. (Copyright © 2022 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.) |
| فهرسة مساهمة: | Keywords: cell therapy; clinical trials; donor screening; immunomodulation; mesenchymal stromal cells; potency; release criteria |
| تواريخ الأحداث: | Date Created: 20220301 Date Completed: 20220426 Latest Revision: 20220520 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1016/j.jcyt.2021.11.009 |
| PMID: | 35227601 |
| قاعدة البيانات: | MEDLINE |
PDF full text from Publisher 
Full Text via ClinicalKey 
Full Text Finder | تدمد: | 1477-2566 |
|---|---|
| DOI: | 10.1016/j.jcyt.2021.11.009 |