scholarly journals Acceleration of Translational Mesenchymal Stromal Cell Therapy Through Consistent Quality GMP Manufacturing

2021 ◽  
Vol 9 ◽  
Author(s):  
Premkumar Jayaraman ◽  
Ryan Lim ◽  
Jacqueline Ng ◽  
Mohan C. Vemuri
Keyword(s):  
Quality Control ◽  
Clinical Trials ◽  
Mesenchymal Stromal Cell ◽  
Stromal Cell ◽  
Raw Materials ◽  
Regulatory Compliance ◽  
Functional Testing ◽  
Materials Selection ◽  
Safety Testing ◽  
Modular Systems

Human mesenchymal stromal cell (hMSC) therapy has been gaining immense interest in regenerative medicine and quite recently for its immunomodulatory properties in COVID-19 treatment. Currently, the use of hMSCs for various diseases is being investigated in >900 clinical trials. Despite the huge effort, setting up consistent and robust scalable manufacturing to meet regulatory compliance across various global regions remains a nagging challenge. This is in part due to a lack of definitive consensus for quality control checkpoint assays starting from cell isolation to expansion and final release criterion of clinical grade hMSCs. In this review, we highlight the bottlenecks associated with hMSC-based therapies and propose solutions for consistent GMP manufacturing of hMSCs starting from raw materials selection, closed and modular systems of manufacturing, characterization, functional testing, quality control, and safety testing for release criteria. We also discuss the standard regulatory compliances adopted by current clinical trials to broaden our view on the expectations across different jurisdictions worldwide.

Regulatory environment for the development of an allogeneic mesenchymal stromal cell product for use in clinical trials

Cytotherapy ◽  
2015 ◽  
Vol 17 (6) ◽  
pp. S25
Author(s):  
Amanda van Beinum ◽  
Irene Watpool ◽  
Shirley H. Mei ◽  
David Allan ◽  
David W. Courtman ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Mesenchymal Stromal Cell ◽  
Stromal Cell ◽  
Regulatory Environment ◽  
Cell Product

scholarly journals Functional heterogeneity of IFN-γ–licensed mesenchymal stromal cell immunosuppressive capacity on biomaterials

2021 ◽  
Vol 118 (35) ◽  
pp. e2105972118
Author(s):  
Brian J. Kwee ◽  
Johnny Lam ◽  
Adovi Akue ◽  
Mark A. KuKuruga ◽  
Kunyu Zhang ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Stromal Cells ◽  
Mesenchymal Stromal Cell ◽  
Stromal Cell ◽  
T Cell Proliferation ◽  
Functional Heterogeneity ◽  
Limited Success ◽  
Therapeutic Properties ◽  
Ifn Γ ◽  
Multiple Donors

Mesenchymal stromal cells (MSCs) are increasingly combined with biomaterials to enhance their therapeutic properties, including their immunosuppressive function. However, clinical trials utilizing MSCs with or without biomaterials have shown limited success, potentially due to their functional heterogeneity across different donors and among different subpopulations of cells. Here, we evaluated the immunosuppressive capacity, as measured by the ability to reduce T-cell proliferation and activation, of interferon-gamma (IFN-γ)–licensed MSCs from multiple donors on fibrin and collagen hydrogels, the two most commonly utilized biomaterials in combination with MSCs in clinical trials worldwide according to ClinicalTrials.gov. Variations in the immunosuppressive capacity between IFN-γ–licensed MSC donors on the biomaterials correlated with the magnitude of indoleamine-2,3-dioxygenase activity. Immunosuppressive capacity of the IFN-γ–licensed MSCs depended on the αV/α5 integrins when cultured on fibrin and on the α2/β1 integrins when cultured on collagen. While all tested MSCs were nearly 100% positive for these integrins, sorted MSCs that expressed higher levels of αV/α5 integrins demonstrated greater immunosuppressive capacity with IFN-γ licensing than MSCs that expressed lower levels of these integrins on fibrin. These findings were equivalent for MSCs sorted based on the α2/β1 integrins on collagen. These results demonstrate the importance of integrin engagement to IFN-γ licensed MSC immunosuppressive capacity and that IFN-γ–licensed MSC subpopulations of varying immunosuppressive capacity can be identified by the magnitude of integrin expression specific to each biomaterial.

scholarly journals Standards of clinical-grade mesenchymal stromal cell preparation and quality control (2020 China Version)

2020 ◽  
Vol 8 (4) ◽  
pp. 197-216
Author(s):  
Shuanglin Xiang
Keyword(s):  
Stem Cells ◽  
Quality Control ◽  
Quality Management ◽  
Cell Therapy ◽  
Clinical Research ◽  
Mesenchymal Stromal Cell ◽  
Stromal Cell ◽  
Human Umbilical Cord ◽  
Clinical Grade ◽  
Cell Preparation

Mesenchymal stromal cells (MSCs) including mesenchymal stem cells to potentially differentiate into different tissue lineages widely exist in various tissues. In recent years, the clinical research and application of MSCs have become more extensive, but no standardized guidelines for the preparation and quality control of clinical-grade MSCs currently exist. To standardize the preparation and quality control of MSCs using the human umbilical cord, placenta, bone marrow, and adipose tissue as sample sources for the Chinese Association of Neurorestoratology (CANR; Preparatory) and the China Committee of International Association of Neurorestoratology (IANR-China Committee) member units, this standard is formulated following the T11/CSSCR 001-2017 General Requirements for Stem Cells, Good Manufacturing Practice Pharmaceutical Products (2010 Edition), Pharmacopoeia of the People's Republic of China (2015 Edition), Guiding Principles for Quality Control of Stem Cell Preparations and Preclinical Research (Trial), Code for Cell Banking Facility Quality Management, Sterile Drug Appendix to Pharmaceutical Production Quality Management Regulations, GMP Appendix — Cell Therapy Products (Draft for Comment), The International Society for Cellular Therapy position statement (2006), and Clinical Cell Therapy Guidelines for Neurorestoration (IANR/CANR 2017). Moreover, this standard includes donor evaluation, sample collection, cell preparation, cell inspection, packaging, labeling, transportation and storage, and quality control. It represents the minimum requirements for clinical-grade mesenchymal stromal cell culture and quality control. Moreover, it will be further optimized following the progress of preclinical and clinical research.

scholarly journals Mesenchymal Stromal Cell-Based Therapy—An Alternative to Arthroplasty for the Treatment of Osteoarthritis? A State of the Art Review of Clinical Trials

2020 ◽  
Vol 9 (7) ◽  
pp. 2062
Author(s):  
Tazio Maleitzke ◽  
Hisham Elazaly ◽  
Christian Festbaum ◽  
Christian Eder ◽  
Daniel Karczewski ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Clinical Trials ◽  
Mesenchymal Stromal Cell ◽  
Stromal Cell ◽  
State Of The Art ◽  
Cochrane Library ◽  
Knee Oa ◽  
Cell Based Therapy ◽  
Joint Disorder ◽  
Effective Source

Osteoarthritis (OA) is the most common degenerative joint disorder worldwide and to date no regenerative treatment has been established in clinical practice. This review evaluates the current literature on the clinical translation of mesenchymal stromal cell (MSC)-based therapy in OA management with a focus on safety, outcomes and procedural specifics. PubMed, Cochrane Library and clinicaltrials.gov were searched for clinical studies using MSCs for OA treatment. 290 articles were initially identified and 42 articles of interest, including a total of 1325 patients, remained for further examination. Most of the included studies used adipose tissue-derived MSCs or bone-marrow-derived MSCs to treat patients suffering from knee OA. MSC-based therapy for knee OA appears to be safe and presumably effective in selected parameters. Yet, a direct comparison between studies was difficult due to a pronounced variance regarding methodology, assessed outcomes and evidence levels. Intensive scientific engagement is needed to identify the most effective source and dosage of MSCs for OA treatment in the future. Consent on outcome measures has to be reached and eventually patient sub-populations need to be identified that will profit most from MSC-based treatment for OA.

Challenges for mesenchymal stromal cell therapies

2019 ◽  
Vol 11 (480) ◽  
pp. eaat2189 ◽  
Author(s):  
Ivan Martin ◽  
Jacques Galipeau ◽  
Charles Kessler ◽  
Katarina Le Blanc ◽  
Francesco Dazzi
Keyword(s):  
Clinical Trials ◽  
Mesenchymal Stromal Cell ◽  
Stromal Cell ◽  
Therapeutic Targets ◽  
Mechanisms Of Action ◽  
Cell Therapies ◽  
Heterogeneous Landscape ◽  
Cell Sources

Clinical trials of mesenchymal stromal cell therapies reveal a challenging heterogeneous landscape, including diverse therapeutic targets, patient categories, cell sources, and potential mechanisms of action.

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