Mesenchymal stromal cell based therapies for the treatment of immune disorders: recent milestones and future challenges

ABSTRACT

Introduction: Mesenchymal stromal cells (MSCs) present unique immunomodulatory properties that make them promising candidates for the treatment of inflammatory and immune disorders. MSC-mediated immunomodulation is a complex combination of mechanisms, in which the secretome plays a fundamental role. The plethora of bioactive molecules MSCs produce, such as indoleamine 2,3-dioxygenase (IDO) or prostaglandin E2 (PGE2), efficiently regulates innate and adaptive immunity. As a result, MSCs have been extensively employed in preclinical studies, leading to the conduction of multiple clinical trials.

Areas covered: This review summarizes the effects of some of the key biomolecules in the MSC secretome and the advances in preclinical studies exploring the treatment of disorders including graft-versus-host disease (GvHD) or inflammatory bowel disease (IBD). Further, late-stage clinical trials and the first MSC-based therapies that recently obtained regulatory approval are discussed.

Expert opinion: Extensive research supports the potential of MSC-based immunomodulatory therapies. However, to establish the bases for clinical translation, the future of study lies in the standardization of protocols and in the development of strategies that boost the therapeutic properties of MSCs.

KEYWORDS:

• IDO
• immunomodulation
• MSC
• PGE2
• secretome

Article highlights

• Mesenchymal stromal cells (MSCs) are promising candidates for the treatment of immune and inflammatory disorders because of their important immunomodulatory properties.

• MSC-mediated immunomodulation is governed by the production of a plethora of bioactive molecules that regulate innate and adaptive immunity.

• Among many other factors, the MSC secretome includes indoleamine 2,3-dioxygenase (IDO), prostaglandin E2 (PGE2), galectin-9 (GAL9) and hepatocyte growth factor (HGF).

• Preclinical studies in multiple disorders have led to the conduction of multiple clinical trials. Despite the majority of them are still in early phases, the success of some late stage clinical trials has resulted in the pioneering regulatory approval of the first MSC-based therapies.

• Further research should focus on the standardization of protocols and in the development of strategies that enhance the immunomodulatory capacity of MSCs.

This box summarizes key points contained in the article.

Box 1. MSC terminology and phenotypic characterization.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

Authors thank for the project SAF2017-82292-R (MINECO) and the support from the Basque Country Government (Grupos Consolidados, No ref: IT907-16). A. Gonzalez-Pujana thanks the Basque Government (Department of Education, Universities and Research) for the PhD grant (PRE_2018_2_0133).