Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Jan 14:9:716853.
doi: 10.3389/fcell.2021.716853. eCollection 2021.

Therapeutic Mesenchymal Stem/Stromal Cells: Value, Challenges and Optimization

Mehdi Najar  1   2 , Rahma Melki  3 , Ferial Khalife  4 , Laurence Lagneaux  1 , Fatima Bouhtit  3   5 , Douaa Moussa Agha  3   5 , Hassan Fahmi  2 , Philippe Lewalle  5 , Mohammad Fayyad-Kazan  6   7 , Makram Merimi  3   5
Affiliations
Review

Therapeutic Mesenchymal Stem/Stromal Cells: Value, Challenges and Optimization

Mehdi Najar et al. Front Cell Dev Biol. .

Abstract

Cellular therapy aims to replace damaged resident cells by restoring cellular and molecular environments suitable for tissue repair and regeneration. Among several candidates, mesenchymal stem/stromal cells (MSCs) represent a critical component of stromal niches known to be involved in tissue homeostasis. In vitro, MSCs appear as fibroblast-like plastic adherent cells regardless of the tissue source. The therapeutic value of MSCs is being explored in several conditions, including immunological, inflammatory and degenerative diseases, as well as cancer. An improved understanding of their origin and function would facilitate their clinical use. The stemness of MSCs is still debated and requires further study. Several terms have been used to designate MSCs, although consensual nomenclature has yet to be determined. The presence of distinct markers may facilitate the identification and isolation of specific subpopulations of MSCs. Regarding their therapeutic properties, the mechanisms underlying their immune and trophic effects imply the secretion of various mediators rather than direct cellular contact. These mediators can be packaged in extracellular vesicles, thus paving the way to exploit therapeutic cell-free products derived from MSCs. Of importance, the function of MSCs and their secretome are significantly sensitive to their environment. Several features, such as culture conditions, delivery method, therapeutic dose and the immunobiology of MSCs, may influence their clinical outcomes. In this review, we will summarize recent findings related to MSC properties. We will also discuss the main preclinical and clinical challenges that may influence the therapeutic value of MSCs and discuss some optimization strategies.

Keywords: challenges; clinical value; mesenchymal stem/stromal cells; optimization; therapeutic features.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

GRAPHICAL ABSTRACT
GRAPHICAL ABSTRACT
The road map for the use of MSCs.
FIGURE 1
FIGURE 1
The nomenclature of MSCs over the time.
FIGURE 2
FIGURE 2
The pre-clinical challenges linked to MSCs. MOC: mechanisms of action.
FIGURE 3
FIGURE 3
The clinical challenges linked to MSCs.
FIGURE 4
FIGURE 4
The clinical optimization of MSC therapy.
See this image and copyright information in PMC

References

    1. Abdul Wahid S. F., Law Z. K., Ismail N. A., Lai N. M. (2019). Cell-based Therapies for Amyotrophic Lateral Sclerosis/motor Neuron Disease. Cochrane Database Syst. Rev. 12, CD011742. 10.1002/14651858.CD011742.pub3 - DOI - PMC - PubMed
    1. Ackema K. B., Charité J. (2008). Mesenchymal Stem Cells from Different Organs Are Characterized by Distinct TopographicHoxCodes. Stem Cell Develop. 17 (5), 979–992. 10.1089/scd.2007.0220 - DOI - PubMed
    1. Ahmadi M., Rezaie J. (2021). Ageing and Mesenchymal Stem Cells Derived Exosomes: Molecular Insight and Challenges. Cell Biochem Funct 39 (1), 60–66. 10.1002/cbf.3602 - DOI - PubMed
    1. Al-Najar M., Khalil H., Al-Ajlouni J., Al-Antary E., Hamdan M., Rahmeh R., et al. (2017). Intra-articular Injection of Expanded Autologous Bone Marrow Mesenchymal Cells in Moderate and Severe Knee Osteoarthritis Is Safe: a Phase I/II Study. J. Orthop. Surg. Res. 12 (1), 190. 10.1186/s13018-017-0689-6 - DOI - PMC - PubMed
    1. Amarnath S., Foley J. E., Farthing D. E., Gress R. E., Laurence A., Eckhaus M. A., et al. (2015). Bone Marrow-Derived Mesenchymal Stromal Cells Harness Purinergenic Signaling to Tolerize Human Th1 Cells In Vivo . Stem Cells 33 (4), 1200–1212. 10.1002/stem.1934 - DOI - PMC - PubMed

LinkOut - more resources