AUTHOR=Soria-Juan Bárbara, Escacena Natalia, Capilla-González Vivian, Aguilera Yolanda, Llanos Lucía, Tejedo Juan R., Bedoya Francisco J., Juan Verónica, De la Cuesta Antonio, Ruiz-Salmerón Rafael, Andreu Enrique, Grochowicz Lukas, Prósper Felipe, Sánchez-Guijo Fermín, Lozano Francisco S., Miralles Manuel, Del Río-Solá Lourdes, Castellanos Gregorio, Moraleda José M., Sackstein Robert, García-Arranz Mariano, García-Olmo Damián, Martín Franz, Hmadcha Abdelkrim, Soria Bernat, Collaborative Working Group “Noma Project Team” TITLE=Cost-Effective, Safe, and Personalized Cell Therapy for Critical Limb Ischemia in Type 2 Diabetes Mellitus JOURNAL=Frontiers in Immunology VOLUME=10 YEAR=2019 URL=https://www.frontiersin.org/articles/10.3389/fimmu.2019.01151 DOI=10.3389/fimmu.2019.01151 ISSN=1664-3224 ABSTRACT=Cell therapy is a progressively growing field that is rapidly moving from preclinical model development to clinical application. Outcomes obtained from clinical trials reveal the therapeutic potential of stem cell-based therapy to deal with unmet medical treatment needs for several disorders with no therapeutic options. Among adult stem cells, mesenchymal stem cells (MSCs) are the leading cell type used in advanced therapies for the treatment of autoimmune, inflammatory and vascular diseases. To date, the safety and feasibility of autologous MSC-based therapy has been established; however, their indiscriminate use has resulted in mixed outcomes in preclinical and clinical studies. While MSCs derived from diverse tissues share common properties depending on the type of clinical application, they markedly differ within clinical trials in terms of efficacy, resulting in many unanswered questions regarding the application of MSCs. Additionally, our experience in clinical trials related to critical limb ischemia pathology (CLI) shows that the therapeutic efficacy of these cells in different animal models has only been partially reproduced in humans through clinical trials. Therefore, it is crucial to develop new research to identify pitfalls, to optimize procedures and to clarify the repair mechanisms used by these cells, as well as to be able to offer a next generation of stem cell that can be routinely used in a cost-effective and safe manner in stem cell-based therapies targeting CLI.