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The ISCT Scientific Signature Series Symposium "Advances in Cell and Gene Therapies for Lung Diseases and Critical Illnesses" was held as an independent symposium in conjunction with the biennial meeting, "Stem Cells, Cell Therapies, and Bioengineering in Lung Biology and Diseases," which took place July 12-15, 2021, at the University of Vermont. This is the third Respiratory System-based Signature Series event; the first 2, "Tracheal Bioengineering, the Next Steps" and "Cellular Therapies for Pulmonary Diseases and Critical Illnesses: State of the Art of European Science," took place in 2014 and 2015, respectively. Cell- and gene-based therapies for respiratory diseases and critical illnesses continue to be a source of great promise and opportunity. This reflects ongoing advancements in understanding of the mechanisms by which cell-based therapies, particularly those using mesenchymal stromal cells (MSCs), can mitigate different lung injuries and the increasing sophistication with which preclinical data is translated into clinical investigations. This also reflects continuing evolution in gene transfer vectors, including those designed for in situ gene editing in parallel with those targeting gene or cell replacement. Therefore, this symposium convened global thought leaders in a forum designed to catalyze communication and collaboration to bring the greatest possible innovation and value of cell- and gene-based therapies for patients with respiratory diseases and critical illnesses., (Copyright © 2022 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)

The Cellular Therapy Coding and Labeling Advisory Group of the International Council for Commonality in Blood Banking Automation and the International Society for Cell & Gene Therapy mesenchymal stromal cell (MSC) committee are providing specific recommendations on abbreviating tissue sources of culture-adapted MSCs. These recommendations include using abbreviations based on the ISBT 128 terminology model that specifies standard class names to distinguish cell types and tissue sources for culture-adapted MSCs. Thus, MSCs from bone marrow are MSC(M), MSCs from cord blood are MSC(CB), MSCs from adipose tissue are MSC(AT) and MSCs from Wharton's jelly are MSC(WJ). Additional recommendations include using these abbreviations through the full spectrum of pre-clinical, translational and clinical research for the development of culture-adapted MSC products. This does not apply to basic research focused on investigating the developmental origins, identity or functionalities of endogenous progenitor cells in different tissues. These recommendations will serve to harmonize nomenclature in describing research and development surrounding culture-adapted MSCs, many of which are destined for clinical and/or commercial translation. These recommendations will also serve to align research and development efforts on culture-adapted MSCs with other cell therapy products., (Copyright © 2021 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)

The field of mesenchymal stromal cell (MSC) biology and clinical cellular therapy has grown exponentially over the last few decades. With discovery of multiple tissue specific sources of stromal cells, invariably being termed MSCs, and their increasing clinical application, there is a need to further delineate the true definition of a mesenchymal stromal cell and to recognise the inherit differences between cell sources; both their potential and limitations. In this review, we discuss the importance of considering every stromal cell source as an independent entity and the need to critically evaluate and appreciate the true phenotype of these cells and their safety when considering their use in novel cell therapies., (Copyright © 2018. Published by Elsevier Inc.)

Background: There is a growing interest in mesenchymal stem cells (MSCs) because they are regarded as good candidates for cell therapy. Adipose tissue represents an easily accessible source to derive mesenchymal stem cells (Ad-MSCs) non-invasively in large numbers. The aim of this study was to evaluate a defined serum-free medium for in vitro expansion of MSCs as a prerequisite for their clinical use., Methods: Adipose tissue was isolated from healthy donors. Cells were isolated and expanded for five passages in serum-free medium (Mesencult-XF) and Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum (DMEM-FBS). MSC morphology, marker expression, viability, population doubling time and differentiation potential toward osteogenic and adipogenic lineages were evaluated. Bone marrow MSCs were included as controls., Results: Ad-MSCs cultured in Mesencult-XF had shorter population doubling time (33.3 ± 13.7 h) compared with those cultured in DMEM-FBS (54.3 ± 41.0 h, P < 0.05). Ad-MSCs cultured in Mesencult-XF displayed a stable morphology and surface marker expression and a higher differentiation potential in comparison to Ad-MSCs cultured in DMEM-FBS., Conclusions: The defined serum-free and xeno-free Mesencult-XF media appear to be a good choice for Ad-MSCs, but it is not as good in supporting culture of bone marrow MSCs when the cells are to be used for clinical purposes., (Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Background Aims: Multipotent mesenchymal stromal cells, also known as mesenchymal stem cells (MSC), can be isolated from adult and fetal tissues. Recently, there has been considerable interest in MSC because they have features favorable for transplantation, namely their multipotency and non-immunogenic properties., Methods: We analyzed how human MSC derived from first-trimester fetal liver and adult bone marrow interact with naive and activated innate natural killer (NK) cells. NK cell function was studied by measuring killing of MSC, as well as degranulation (CD107a) induced by MSC. To assess the importance of NK cell killing, expression of surface epitopes was analyzed by flow cytometry on MSC before and after stimulation with interferon (IFN)γ., Results: Fetal and adult MSC express several ligands to activating NK cell receptors as well as low levels of HLA class I, with large inter-individual variation. Naive peripheral blood NK cells did not lyse fetal or adult MSC, whereas interleukin (IL)2 activated allogeneic as well as autologous NK cells did. Pre-incubation of MSC with IFN-γ increased their levels of HLA class I, protecting them from NK cell recognition. Fetal and adult MSC were preferably killed via the tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and Fas ligand (FasL) pathways, respectively. Blocking NKG2D reduced NK cell degranulation in both fetal and adult MSC., Conclusions: Fetal and adult MSC differ in their interactions with NK cells. Both fetal and adult MSC are susceptible to lysis by activated NK cells, which may have implications for the use of MSC in cell therapy.

Abstract We address the issue of the potential for malignant transformation of cultured mesenchymal stromal cells (MSC) commonly used in clinical cell-therapy protocols and describe the culture conditions under which tumorigenesis is likely to be an extremely uncommon event.

Background Aims: Mesenchymal stromal cells (MSC) can be expanded in vitro for clinical use and have been evaluated in clinical trials as immunosuppressants and to heal damaged tissues. We investigated the impact of freezing and prolonged storage on cell viability, proliferation and immunosuppression in vitro., Methods: MSC were expanded from bone marrow (BM) of healthy subjects according to standard protocols in the presence of fetal calf serum (FCS). The immunosuppressive potential of MSC was analyzed in mixed lymphocyte cultures (MLC) and after stimulation with phytohemagglutinin (PHA)., Results: Expansion of frozen mononuclear cells (MNC) diminished MSC yield after expansion compared with plating of fresh MNC. MSC derived from frozen MNC were also less immunosuppressive. MSC harvested at various passages after expansion in vivo suppressed lymphocyte proliferation equally. Pooling of MSC from several donors generated higher and more stable suppression in both MLC and after PHA stimulation. After passage 1, plating at lower densities in 20% FCS increased cell expansion of MSC up to 25-fold compared with standard conditions., Conclusions: MNC should not be frozen prior to MSC expansion. Decreased replating density and increased FCS levels generate higher numbers of MSC. Freezing of ex vivo-expanded MSC for >30 months did not affect cell viability or the ability to suppress lymphocyte proliferation. For effective immunosuppression in vitro MSC should be stored for less than 6 months and pooled from two or three donors.