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Review
. 2023 May 12:14:1148932.
doi: 10.3389/fphys.2023.1148932. eCollection 2023.

FTY720 in immuno-regenerative and wound healing technologies for muscle, epithelial and bone regeneration

Monica Behara  1 , Steven Goudy  1   2
Affiliations
Review

FTY720 in immuno-regenerative and wound healing technologies for muscle, epithelial and bone regeneration

Monica Behara et al. Front Physiol. .

Abstract

In 2010, the FDA approved the administration of FTY720, S1P lipid mediator, as a therapy to treat relapsing forms of multiple sclerosis. FTY720 was found to sequester pro-inflammatory lymphocytes within the lymph node, preventing them from causing injury to the central nervous system due to inflammation. Studies harnessing the anti-inflammatory properties of FTY720 as a pro-regenerative strategy in wound healing of muscle, bone and mucosal injuries are currently being performed. This in-depth review discusses the current regenerative impact of FTY720 due to its anti-inflammatory effect stratified into an assessment of wound regeneration in the muscular, skeletal, and epithelial systems. The regenerative effect of FTY720 in vivo was characterized in three animal models, with differing delivery mechanisms emerging in the last 20 years. In these studies, local delivery of FTY720 was found to increase pro-regenerative immune cell phenotypes (neutrophils, macrophages, monocytes), vascularization, cell proliferation and collagen deposition. Delivery of FTY720 to a localized wound environment demonstrated increased bone, muscle, and mucosal regeneration through changes in gene and cytokine production primarily by controlling the local immune cell phenotypes. These changes in gene and cytokine production reduced the inflammatory component of wound healing and increased the migration of pro-regenerative cells (neutrophils and macrophages) to the wound site. The application of FTY720 delivery using a biomaterial has demonstrated the ability of local delivery of FTY720 to promote local wound healing leveraging an immunomodulatory mechanism.

Keywords: FTY720; immunomodulation; multiple sclerosis; regenerative medicine; regenerative micro-environment; tissue engineering; wound healing.

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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

None
A schematic summarizing the current delivery mechanisms of FTY720, organ systems and regenerative models reviewed and hall marks of wound healing upon FTY720 delivery.
FIGURE 1
FIGURE 1
Lymphoid tissue. Describes the mechanism of action of FTY720 (Shown in red). Lymphocytes enter the lymph node from the blood and afferent lymph. The S1P receptor is externalized on the cell surface where it binds to the bioactive FTY720P resulting in the internalization and degradation of the receptor, preventing lymphocyte egress into the efferent lymph.
See this image and copyright information in PMC

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Grants and funding

Research reported in this publication was supported by the Oral Maxillofacial Surgery Foundation (Funding ID: 2591) and the National Institute of Dental and Craniofacial Research of the National Institutes of Health under award number R01 DE028905-03.

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