Considerations for Clinical Use of Mesenchymal Stromal Cells

Hmadcha, Abdelkrim; Soria, Bernat; Tejedo, Juan R.; Bedoya, Francico J.; Sempere-Ortells, Jose Miguel; Smani, Tarik

doi:10.1007/978-981-16-6016-0_3-1

Abdelkrim Hmadcha^2,3,10,
Bernat Soria^3,5,
Juan R. Tejedo^4,10,
Francico J. Bedoya^4,10,
Jose Miguel Sempere-Ortells⁶ &
…
Tarik Smani^7,8,9

61 Accesses

Abstract

The clinical application of stem cells continues to fascinate the scientific and clinical communities. Despite the controversies surrounding this field, it is clear that stem cells have revolutionized regenerative medicine. Cell therapy is a progressively growing field that is moving fast from preclinical model development to clinical application. In this regard, outcomes obtained from clinical trials reveal the therapeutic potential of stem cell-based therapy that deals with unmet medical treatment for several disorders with no therapeutic alternatives. The application of stem cells in regenerative medicine is addressing a wide range of clinical conditions using various types of stem 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 multi-differentiation, as well as by their anti-inflammatory, anti-proliferative, immunomodulatory, trophic, and pro-angiogenic properties. Various diseases have been successfully treated by MSCs in animal models. Additionally, hundreds of clinical trials related to the potential benefits of MSCs are in progress or have concluded satisfactorily. 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. Therefore, collecting information regarding the characteristics of MSCs obtained from different sources and the influence of other medical and physiological conditions on MSCs is important for assuring the feasibility, safety, and efficacy of cell-based therapies. This chapter will update and discuss the state of the art in MSCs’ cell-based therapies and provide relevant information regarding factors to consider for the clinical application of MSCs.

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Abbreviations

Ad-MSCs:: Adipose tissue-derived MSCs
AGEs:: Advanced glycation end products
ATMPs:: Advanced therapy medicinal products
bFGF:: Basic fibroblast growth factor
BM-MSCs:: Bone marrow-derived MSCs
CAFs:: Cancer-associated fibroblasts
Cas9:: CRISPR-associated protein 9
CCL:: Chemokine (C-C motif) ligand
CFU-F:: Colony-forming unit fibroblast
CRISPR:: Clustered regularly interspaced short palindromic repeats
CXCL12:: C-X-C motif chemokine 12 (or SDF1)
Dkk-1:: Dickkopf-1
ECs:: Endothelial cells
EMA:: European Medicines Agency
ESCs:: Embryonic stem cells
EVs:: Extracellular vesicles
FBS:: Fetal bovine serum
FDA:: Food and Drug Administration
GM-CSF:: Granulocyte-macrophage colony-stimulating factor
GMP:: Good manufacturing practice
GPS:: Glycotransferase-programmed stereo substitution
GVHD:: Graft-versus-host diseases
GVL:: Graft-versus-leukemia
HCELL:: Hematopoietic cell E-selectin/L-selectin ligand
HGF:: Hepatocyte growth factor
HLA-DR:: Human leukocyte antigen-DR isotype
HLA-G5:: Human leukocyte antigen-G5
HSCT:: Hematopoietic stem cell transplantation
IBMIR:: Instant blood-mediated inflammatory reaction
ICAM-2:: Intercellular adhesion molecule 2
IDO:: Indoleamine-2,3-dioxygenase
IFN-γ:: Interferon-gamma
IGF-1:: Insulin-like growth factor 1
IL:: Interleukin
IL-1α:: Interleukin-1 alpha
IL-1β:: Interleukin-1 beta
iPSCs:: Induced pluripotent stem cells
ISCT:: International Society for Cellular Therapy
ITP:: Immune thrombocytopenic purpura
LFA-3:: Lymphocyte function-associated antigen 3 (or CD58)
MCP-1:: Monocyte chemoattractant protein 1
MHC-HLA:: Major histocompatibility complex-human leukocyte antigen
MMP-2:: Matrix metalloproteinase 2
MSCs:: Mesenchymal stromal cells
PAI-1:: Plasminogen activator inhibitor-1
PDGF:: Platelet-derived growth factor
PD-MSCs:: Placenta-derived MSCs
PGE-2:: Prostaglandin-E2
RA:: Rheumatoid arthritis
SDF-1:: Stromal cell-derived factor 1
SLE:: Systemic lupus erythematosus
SSc:: Systemic sclerosis
STC1:: Stanniocalcin-1
TALENs:: Transcription activator nucleases
TbRIII:: Type III TGF-β receptor
TGF-β:: Transforming growth factor beta
TNF-α:: Tumor necrosis factor alpha
tPA:: Tissue plasminogen activator
TRAIL:: TNF-related apoptosis-inducing ligand
Trx1:: Thioredoxin-1
TSG-6:: Tumor necrosis factor-stimulated gene-6
UCB-MSCs:: Umbilical cord-derived MSCs
VCAM-1:: Vascular cell adhesion protein 1
VEGF:: Vascular endothelial growth factor
ZFNs:: Zinc finger nucleases

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Department of Biotechnology, University of Alicante, Alicante, Spain
Abdelkrim Hmadcha
University of Pablo de Olavide, Sevilla, Spain
Abdelkrim Hmadcha & Bernat Soria
Department of Molecular Biology and Biochemical Engineering, University of Pablo de Olavide, Sevilla, Spain
Juan R. Tejedo & Francico J. Bedoya
Department of Physiology, Institute of Bioengineering-Alicante Institute for Health and Biomedical Research (ISABIAL), University Miguel Hernández School of Medicine, Alicante, Spain
Bernat Soria
Department of Biotechnology, Immunology Division, University of Alicante, Alicante, Spain
Jose Miguel Sempere-Ortells
Cardiovascular Pathophysiology, Institute of Biomedicine of Seville (IBiS), University Hospital of Virgen del Rocío/University of Seville/CSIC, Seville, Spain
Tarik Smani
Department of Medical Physiology and Biophysics, University of Seville, Seville, Spain
Tarik Smani
Biomedical Research Networking Centers of Cardiovascular Diseases (CIBERCV), Madrid, Spain
Tarik Smani
Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Madrid, Spain
Abdelkrim Hmadcha, Juan R. Tejedo & Francico J. Bedoya

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Bernat Soria
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Jose Miguel Sempere-Ortells
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Department of Basic Sciences, Sulaiman AlRajhi University, Al Bukairiyah, Saudi Arabia
Khawaja H. Haider

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Division of Cardiac Surgery, Health Sciences North, Northern Ontario School of Medicine, Sudbury, ON, Canada
Rony Atoui
Unidad de Terapia Celular y Medicina Regenerativa, Servicio de Hematología y Hemoterapia, Hospital Universitario Central de Asturias HUCA, Instituto de Investigación Biosanitaria del Principado de Asturias, Universidad de Oviedo, Asturias, Spain
Maria Alvarez-Viejo
Department of Basic Sciences, Sulaiman AlRajhi University, Al Bukayriyah, Kingdom of Saudi Arabia
Khawaja Husnain Haider

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Hmadcha, A., Soria, B., Tejedo, J.R., Bedoya, F.J., Sempere-Ortells, J.M., Smani, T. (2022). Considerations for Clinical Use of Mesenchymal Stromal Cells. In: Haider, K.H. (eds) Handbook of Stem Cell Therapy. Springer, Singapore. https://doi.org/10.1007/978-981-16-6016-0_3-1

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DOI: https://doi.org/10.1007/978-981-16-6016-0_3-1
Received: 11 September 2021
Accepted: 16 November 2021
Published: 21 May 2022
Publisher Name: Springer, Singapore
Print ISBN: 978-981-16-6016-0
Online ISBN: 978-981-16-6016-0
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