Editorial: Mesenchymal Stromal Cells: Preclinical and Clinical Challenges

Mesenchymal Stromal Cells: Preclinical and Clinical ChallengesFor the past 20 years, mesenchymal stromal cells (MSCs) has become the most studied cell population in the development of adult cell therapies for disease treatment (Keshtkar et al., 2018;Han et al., 2019).MSCs can differentiate into many types of cells (neurons, hepatocytes, myoblast . . . ) and this is one reason why MSCs hold great promise to the treatment of many immune diseases, cardiac and neurological injuries, and tissue regenerative applications (Hwang et al., 2009).Although MSC research discoveries brought new information, the road for cell therapy approval is still at its dawn.Due to the insurgence of MSC therapies, federal agencies with regulatory oversight to healthcare such as the Food and Drug Administration, European Medical Agency, Pharmaceuticals and Medical Devices Agency, Federal Service for Surveillance in Healthcare, etc. have adapted and continue to update their guidelines as needed (Mendicino et al., 2014;Corbett et al., 2017;Pigeau et al., 2018;Stroncek et al., 2022).Similarly, cell therapy manufacturers and suppliers had to adapt quickly in establishing and adopting best practices that ensure safety, quality, and reproducibility of products and raw materials destined to be used in cell therapy manufacturing.Even so, many questions have surfaced around preclinical tests, scalability of MSC production and clinical application, reproducibility of the results, better characterization of the MSCs, the need for development of defined culture media and GMP compliant animal-free components, ancillary materials, and the development of 3D structures mimicking the tissue organization.Friedenstein reported the first fibroblastic-like and spindle-shaped cells to differentiate into other type of cells: chondrocyte and osteoblast (Friedenstein et al., 1968;Friedenstein et al., 1974).MSCs have been isolated from different tissues: adipose tissue, dental pulp, periosteum, Wharton's jelly, umbilical cord (Zuk et al., 2001;Nagamura-Inoue and He, 2014).Due to terminology discrepancies, one of the first task will be to use the exact terminology of MSCs depending on their functional attributes (Bhartiya, 2018).In addition of the Dominici minimal criteria, additional criteria were added for the MSC characterization like MSC responsive to INF-g, TNF-a, indoleamine 2,3 dioxygenase etc (Dominici et al., 2006;Bhartiya, 2018), thanks to the formation of international consortium among expert in MSCs.As mentioned by Najar et al, Wright et al. and Jayaraman et al., the identification of additional MSC markers will strongly support consistency of data obtained from studies.However, in vitro, and in vivo results obtained in clinical trials are still not consistent due to lot-to-lot variations, quality of the cells, variability among the donors.To decrease the variability among studies and to increase the reproducibility, standardization of the isolation, identification of additional surface markers, methodology of MSC expansion must be established (Stroncek et al., 2020).A recent study showed that, even if the laboratories use MSCs from the same material source, MSCs showed different behavior in terms of viability after thawing and different transcriptome due to different methodologies used in the lab and donor source