Front Immunol. 2019 Jun 4;10:1151. doi: 10.3389/fimmu.2019.01151. eCollection 2019.

Cost-Effective, Safe, and Personalized Cell Therapy for Critical Limb Ischemia in Type 2 Diabetes Mellitus.

Soria-Juan B¹, Escacena N², Capilla-González V², Aguilera Y², Llanos L¹, Tejedo JR^2,3, Bedoya FJ^2,3, Juan V⁴, De la Cuesta A⁵, Ruiz-Salmerón R⁶, Andreu E⁷, Grochowicz L⁷, Prósper F⁷, Sánchez-Guijo F⁸, Lozano FS⁸, Miralles M⁹, Del Río-Solá L¹⁰, Castellanos G¹¹, Moraleda JM¹¹, Sackstein R¹², García-Arranz M¹, García-Olmo D¹, Martín F^2,3, Hmadcha A^2,3, Soria B^2,3; Collaborative Working Group “Noma Project Team”.

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.