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

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

Fecha de la publicación: 04/06/2019

Autor: Bárbara Soria-Juan (1), Natalia Escacena (2), Vivian Capilla-González (2), Yolanda Aguilera (2), Lucía Llanos (1), Juan R Tejedo (2, 3), Francisco J Bedoya (2, 3), Verónica Juan (4), Antonio De la Cuesta (5), Rafael Ruiz-Salmerón (6), Enrique Andreu (7), Lukas Grochowicz (7), Felipe Prósper (7), Fermín Sánchez-Guijo (8), Francisco S Lozano (8), Manuel Miralles (9), Lourdes Del Río-Solá (10), Gregorio Castellanos (11), José M Moraleda (11), Robert Sackstein (12), Mariano García-Arranz (1), Damián García-Olmo (1), Franz Martín (2, 3), Abdelkrim Hmadcha (2, 3), Bernat Soria (2, 3), Collaborative Working Group “Noma Project Team”

Palabras clave: cell-based therapy, cellular medicaments, clinical trials, cost-effective, Critical limb ischemia, diabetes



1Fundación Jiménez Díaz Health Research Institute, Madrid, Spain.

2Department of Regeneration and Cell Therapy, Andalusian Center for Molecular Biology and Regenerative Medicine (CABIMER), University of Pablo de Olavide-University of Seville-CSIC, Seville, Spain.

3Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Madrid, Spain.

4Andalusian eHealth Library, Sevilla, Spain.

5Unidad de Isquemia Crónica de Miembros Inferiores, Hospital Victoria Eugenia de la Cruz Roja, Sevilla, Spain.

6Servicio de Cardiología, Hospital Universitario Virgen Macarena, Sevilla, Spain.

7Clínica Universidad de Navarra, Pamplona, Spain.

8IBSAL-Hospital Universitario Salamanca, Salamanca, Spain.

9Department of Surgery, University of Valencia, Valencia, Spain.

10Cirugía Vascular, Hospital Universitario de Valladolid, Valladolid, Spain.

11Servicio Hematología y Hemoterapia, Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain.

12Herbert Wertheim College of Medicine, Florida International University, Miami, FL, United States.


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.