The International Society for Cell and Gene Therapy MSC Committee Publishes its Perspectives on ISO/TS22859:2022 and ISO24651:2022 with Details of their Extensive Input in the Development of these International Standards.
Dr. Mikey Creane, PhD
Regenerative Medicine Institute
University of Galway
Dr. Nisha Durand, PhD
Center for Regenerative Medicine, Mayo Clinic
Jacksonville, FL, United States
The International Society for Cell and Gene Therapy (ISCT) announces its recent publication detailing its perspectives on the International Standards Organisation (ISO)/Technical Committee (TC) 276 Biobanking standards for bone marrow and umbilical cord tissue-derived Mesenchymal Stromal Cells (MSCs) used for the purposes of research and development (R&D).
This ISCT-commissioned paper, written by the ISCT MSC Committee and led by Dr. Sowmya Viswanathan, provides a concise overview of the development of international consensus standards with specific insights into the path followed in the creation of the technical biobanking standard ISO/TS22859:2022 for Wharton’s jelly derived MSCs and the biobanking standard ISO24651:2022 for bone marrow-derived MSCs . Dr Viswanathan, acting as the formal elected liaison between ISCT and ISO TC276 provided extensive written input on behalf of the ISCT MSC and Executive Committees during all of the drafting stages of these standards over several years.
Why was there a need to develop these international standards? Despite the MSC field reaching scientific maturity with about 1,616 clinical trials and approved MSC products in Canada, Europe and Oceania, there remains a lack of consensus on isolation and characterization protocols for these cells. Acknowledging the overt need for a standard document that provides R&D labs worldwide with specific recommendations on the nomenclature and characterization of MSCs at the R&D stage, ISO/TS 22859:2022 and ISO24651:2022 were created. In a bid to create harmonization amongst R&D labs and organizations worldwide that biobank MSCs, both standards provide consensus-based recommendations for the tissue collection processes, cell isolation, cell characterization and quality control assays. In addition, guidance is also provided on how to cryopreserve, store, thaw and transport the isolated MSCs.
Discussing the scope of ISO/TS22859:2022 and ISO24651:2022, with both documents centring their attention on culture-expanded MSCs, the ISCT MSC committee highlights the most important features of the ISO standards. Analogous to the MSC Committee position papers [2,3] on the nomenclature of MSCs, ISO/TS22859 and ISO24651 clearly define and demarcate the differences between Mesenchymal Stromal Cells and Mesenchymal Stem cells. In addition, both standards acknowledge the ISCT recommendation that MSCs derived from Whartons Jelly and bone marrow should contain the suffix abbreviations MSC(WJ) and MSC(M), respectively.
Whilst ISCT does acknowledge that adaption of these standardized abbreviations may take time to come into effect in academic centres, and public and private organizations, it represents a step forward in achieving a consensus agreement on MSC nomenclature and characterization for R&D purposes. Although these documents are biobanking standards, they contain well-defined characterization sections to which the ISCT MSC Committee has made comprehensive contributions. These sections, detailing recommended matrices of cell identity, gene expression, soluble factor expression and functional immunomodulatory assays, represent the ISCT MSC Committee’s position that such MSC characterization should be assessed using a matrix model of assays [4,5]. Notably, these standards do not provide guidance on MSC manufacturing protocols but do provide robust recommendations on the multivariate characterization of MSCs which can be used to evaluate different manufacturing strategies.
ISCT welcomes the creation and publication of ISO/TS22859:2022 and ISO24651:2022 as they represent a progressive advancement in the standardization and characterization of MSCs used at an R&D level. Notwithstanding that these are voluntary standards, the ISCT MSC committee envisions that the uptake and adoption of the suggested practices detailed in these standards will be an organic process, similar to what occurred previously with the ISCT MSC Committee Position Statement paper: “Minimal Criteria for Defining Multipotent Mesenchymal Stromal Cells”. This ISCT position paper has received more than 11,000 citations since its first publication in Cytotherapy in 2006.
The ISCT MSC Committee went on to explain that as our understanding of MSC biology deepens, with the discovery of new active substances and the identification of the key quality parameters essential to the efficacy of the MSCs, technical revisions will be required to specify sections of the standards. Consequently, these standards should be viewed as living documents that will be edited accordingly using consensus-driven revision processes. There are formal mechanisms for the revision process for ISO/TS, which take place every 3 years following publication and every 5 years for ISO standards.
Although adherence to these standards is not a formal regulatory requirement, the ISCT MSC committee would like to encourage researchers worldwide to adopt the practices highlighted in these standards to ensure that the highest standards are consistently applied to the development of MSC therapeutics at the R&D stages. If you are interested to learn more about the ISCT MSC Committees perspectives on ISO/TS22859:2022 and ISO24651:2022 and their involvement in the development of these international standards, you can access the full ISCT Committee paper via the Cytotherapy website here.
1. Viswanathan S, Blanc KL, Ciccocioppo R, Dagher G, Filiano AJ, Galipeau J, et al. An International Society for Cell and Gene Therapy Mesenchymal Stromal Cells (MSC) Committee perspectives on International Standards Organization/Technical Committee 276 Biobanking Standards for bone marrow-MSCs and umbilical cord tissue-derived MSCs for research purposes. Cytotherapy. 2023:S1465-3249(23)00100-7.
2. Viswanathan S, Shi Y, Galipeau J, Krampera M, Leblanc K, Martin I, et al. Mesenchymal stem versus stromal cells: International Society for Cell & Gene Therapy (ISCT) Mesenchymal Stromal Cell committee position statement on nomenclature. Cytotherapy 2019;21(10):1019–24.
3. Viswanathan S, Ciccocioppo R, Galipeau J, Krampera M, Blanc KL, Martin I, et al. Consensus International Council for Commonality in Blood Banking AutomationInternational Society for Cell & Gene Therapy statement on standard nomenclature abbreviations for the tissue of origin of mesenchymal stromal cells. Cytotherapy 2021;23(12):1060–3.
4. Galipeau J, Krampera M, Leblanc K, Nolta JA, Phinney DG, Shi Y, et al. Mesenchymal stromal cell variables influencing clinical potency: the impact of viability, fitness, route of administration and host predisposition. Cytotherapy 2021;23 (5):368–72.
5. Galipeau J, Krampera M, Barrett J, Dazzi F, Deans RJ, DeBruijn J, et al. International Society for Cellular Therapy perspective on immune functional assays for mesenchymal stromal cells as potency release criterion for advanced phase clinical trials. Cytotherapy 2016;18(2):151–9.