Bottlenecks in the efficient use of advanced therapy medicinal products based on mesenchymal stromal cells

Mesenchymal stromal cells (MSCs) have been established as promising candidate sources of universal donor cells for cell therapy due to their contributions to tissue and organ homeostasis, repair, and support by self-renewal and multidifferentiation, as well as by their anti-inflammatory, antiproliferative, immunomodulatory, trophic, and proangiogenic properties. Various diseases have been treated by MSCs in animal models. Additionally, hundreds of clinical trials related to the potential benefits of MSCs are in progress. However, although all MSCs are considered suitable to exert these functions, dissimilarities have been found among MSCs derived from different tissues. The same levels of efficacy and desired outcomes have not always been achieved in the diverse studies that have been performed thus far. Moreover, autologous MSCs can be affected by the disease status of patients, compromising their use. Therefore, collecting information regarding the characteristics of MSCs obtained from different sources and the influence of the host (patient) medical conditions on MSCs is important for assuring the safety and efficacy of cell-based therapies. This review provides relevant information regarding factors to consider for the clinical application of MSCs.The authors are supported by the Fundacion Progreso y ´ Salud, Consejer´ıa de Salud, Junta de Andaluc´ıa; FEDER cofunded grants from Consejer´ıa de Innovacion Ciencia y ´ Empresa, Junta de Andaluc´ıa (Grants CTS-6505; INP-2011- 1615-900000); FEDER cofunded grants from Instituto de Salud Carlos III (Red TerCel-Grant RD12/0019/0028; PI10/ 00964 and PI14/01015) and the Ministry of Health and Consumer Affairs (Advanced Therapies Program Grant TRA- 120); SUDOE Program-BIOREG (Regenerative Medicine Network-SOE3/P1/E750) and ACTION Cost (European Cooperation in Science and Technology-BM1305). Support from FSED and FAID allowed access to databanks. CIBERDEM is an initiative of the Instituto de Salud Carlos IIIPeer Reviewe