Frontiers in Cell and Developmental Biology (Mar 2021)
The Current Status of Mesenchymal Stromal Cells: Controversies, Unresolved Issues and Some Promising Solutions to Improve Their Therapeutic Efficacy
- David García-Bernal,
- David García-Bernal,
- Mariano García-Arranz,
- Mariano García-Arranz,
- Rosa M. Yáñez,
- Rosa M. Yáñez,
- Rosa M. Yáñez,
- Rosario Hervás-Salcedo,
- Rosario Hervás-Salcedo,
- Rosario Hervás-Salcedo,
- Alfonso Cortés,
- Alfonso Cortés,
- María Fernández-García,
- María Fernández-García,
- María Fernández-García,
- Miriam Hernando-Rodríguez,
- Miriam Hernando-Rodríguez,
- Miriam Hernando-Rodríguez,
- Óscar Quintana-Bustamante,
- Óscar Quintana-Bustamante,
- Óscar Quintana-Bustamante,
- Juan A. Bueren,
- Juan A. Bueren,
- Juan A. Bueren,
- Damián García-Olmo,
- Damián García-Olmo,
- Jose M. Moraleda,
- Jose M. Moraleda,
- José C. Segovia,
- José C. Segovia,
- José C. Segovia,
- Agustín G. Zapata,
- Agustín G. Zapata
Affiliations
- David García-Bernal
- Hematopoietic Transplant and Cellular Therapy Unit, Medicine Department, Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca, University of Murcia, Murcia, Spain
- David García-Bernal
- Spanish Network of Cell Therapy (TerCel), Instituto de Salud Carlos III, Madrid, Spain
- Mariano García-Arranz
- Spanish Network of Cell Therapy (TerCel), Instituto de Salud Carlos III, Madrid, Spain
- Mariano García-Arranz
- Instituto de Investigación Sanitaria-Fundación Jiménez Díaz (IIS-FJD, Autonomous University of Madrid (UAM)), Madrid, Spain
- Rosa M. Yáñez
- Spanish Network of Cell Therapy (TerCel), Instituto de Salud Carlos III, Madrid, Spain
- Rosa M. Yáñez
- Advanced Therapies Mixed Unit, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz (IIS-FJD, Autonomous University of Madrid (UAM)), Madrid, Spain
- Rosa M. Yáñez
- Centre for Cytometry and Fluorescence Microscopy, Complutense University, Madrid, Spain
- Rosario Hervás-Salcedo
- Spanish Network of Cell Therapy (TerCel), Instituto de Salud Carlos III, Madrid, Spain
- Rosario Hervás-Salcedo
- Advanced Therapies Mixed Unit, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz (IIS-FJD, Autonomous University of Madrid (UAM)), Madrid, Spain
- Rosario Hervás-Salcedo
- Centre for Cytometry and Fluorescence Microscopy, Complutense University, Madrid, Spain
- Alfonso Cortés
- Spanish Network of Cell Therapy (TerCel), Instituto de Salud Carlos III, Madrid, Spain
- Alfonso Cortés
- Hematopoietic Innovative Therapies Division, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas and Centro de Investigación Biomédica en Red de Enfermedades Raras, Madrid, Spain
- María Fernández-García
- Spanish Network of Cell Therapy (TerCel), Instituto de Salud Carlos III, Madrid, Spain
- María Fernández-García
- Advanced Therapies Mixed Unit, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz (IIS-FJD, Autonomous University of Madrid (UAM)), Madrid, Spain
- María Fernández-García
- Centre for Cytometry and Fluorescence Microscopy, Complutense University, Madrid, Spain
- Miriam Hernando-Rodríguez
- Spanish Network of Cell Therapy (TerCel), Instituto de Salud Carlos III, Madrid, Spain
- Miriam Hernando-Rodríguez
- Advanced Therapies Mixed Unit, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz (IIS-FJD, Autonomous University of Madrid (UAM)), Madrid, Spain
- Miriam Hernando-Rodríguez
- Centre for Cytometry and Fluorescence Microscopy, Complutense University, Madrid, Spain
- Óscar Quintana-Bustamante
- Spanish Network of Cell Therapy (TerCel), Instituto de Salud Carlos III, Madrid, Spain
- Óscar Quintana-Bustamante
- Advanced Therapies Mixed Unit, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz (IIS-FJD, Autonomous University of Madrid (UAM)), Madrid, Spain
- Óscar Quintana-Bustamante
- Centre for Cytometry and Fluorescence Microscopy, Complutense University, Madrid, Spain
- Juan A. Bueren
- Spanish Network of Cell Therapy (TerCel), Instituto de Salud Carlos III, Madrid, Spain
- Juan A. Bueren
- Advanced Therapies Mixed Unit, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz (IIS-FJD, Autonomous University of Madrid (UAM)), Madrid, Spain
- Juan A. Bueren
- Centre for Cytometry and Fluorescence Microscopy, Complutense University, Madrid, Spain
- Damián García-Olmo
- Spanish Network of Cell Therapy (TerCel), Instituto de Salud Carlos III, Madrid, Spain
- Damián García-Olmo
- Instituto de Investigación Sanitaria-Fundación Jiménez Díaz (IIS-FJD, Autonomous University of Madrid (UAM)), Madrid, Spain
- Jose M. Moraleda
- Hematopoietic Transplant and Cellular Therapy Unit, Medicine Department, Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca, University of Murcia, Murcia, Spain
- Jose M. Moraleda
- Spanish Network of Cell Therapy (TerCel), Instituto de Salud Carlos III, Madrid, Spain
- José C. Segovia
- Spanish Network of Cell Therapy (TerCel), Instituto de Salud Carlos III, Madrid, Spain
- José C. Segovia
- Advanced Therapies Mixed Unit, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz (IIS-FJD, Autonomous University of Madrid (UAM)), Madrid, Spain
- José C. Segovia
- Centre for Cytometry and Fluorescence Microscopy, Complutense University, Madrid, Spain
- Agustín G. Zapata
- Spanish Network of Cell Therapy (TerCel), Instituto de Salud Carlos III, Madrid, Spain
- Agustín G. Zapata
- Department of Cell Biology, Complutense University, Madrid, Spain
- DOI
- https://doi.org/10.3389/fcell.2021.650664
- Journal volume & issue
-
Vol. 9
Abstract
Mesenchymal stromal cells (MSCs) currently constitute the most frequently used cell type in advanced therapies with different purposes, most of which are related with inflammatory processes. Although the therapeutic efficacy of these cells has been clearly demonstrated in different disease animal models and in numerous human phase I/II clinical trials, only very few phase III trials using MSCs have demonstrated the expected potential therapeutic benefit. On the other hand, diverse controversial issues on the biology and clinical applications of MSCs, including their specific phenotype, the requirement of an inflammatory environment to induce immunosuppression, the relevance of the cell dose and their administration schedule, the cell delivery route (intravascular/systemic vs. local cell delivery), and the selected cell product (i.e., use of autologous vs. allogeneic MSCs, freshly cultured vs. frozen and thawed MSCs, MSCs vs. MSC-derived extracellular vesicles, etc.) persist. In the current review article, we have addressed these issues with special emphasis in the new approaches to improve the properties and functional capabilities of MSCs after distinct cell bioengineering strategies.
Keywords