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Influence of Dipeptidyl Peptidase-4 (DPP4) on Mesenchymal Stem-Cell (MSC) Biology: Implications for Regenerative Medicine – Review

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Abstract

Dipeptidyl peptidase IV (DPP4) is a ubiquitous protease that can be found in membrane-anchored or soluble form. Incretins are one of the main DPP4 substrates. These hormones regulate glucose levels, by stimulating insulin secretion and decreasing glucagon production. Because DPP4 levels are high in diabetes, DPP4 inhibitor (DPP4i) drugs derived from gliptin are widespread used as hypoglycemic agents for its treatment. However, as DPP4 recognizes other substrates such as chemokines, growth factors and neuropeptides, pleiotropic effects have been observed in patients treated with DPP4i. Several of these substrates are part of the stem-cell niche. Thus, they may affect different physiological aspects of mesenchymal stem-cells (MSC). They include viability, differentiation, mobilization and immune response. MSC are involved in tissue homeostasis and regeneration under both physiological and pathological conditions. Therefore, such cells and their secretomes have a high clinical potential in regenerative medicine. In this context, DPP4 activity may modulate different aspects of MSC regenerative capacity. Therefore, the aim of this review is to analyze the effect of different DPP4 substrates on MSC. Likewise, how the regulation of DPP4 activity by DPP4i can be applied in regenerative medicine. That includes treatment of cardiovascular and bone pathologies, cutaneous ulcers, organ transplantation and pancreatic beta-cell regeneration, among others. Thus, DPP4i has an important clinical potential as a complement to therapeutic strategies in regenerative medicine. They involve enhancing the differentiation, immunomodulation and mobilization capacity of MSC for regenerative purposes.

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Acknowledgements

This work is supported by grants PI15/01857, PI18/01659 and CIBER “Fragilidad y Envejecimiento Saludable” (CIBERFES) of “Instituto de Salud Carlos III” (ISCIII), “Ministerio de Economía y Competitividad” (MINECO), Spain and European Union (EU).

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  1. Unidad de Gestión Clínica de Endocrinología y Nutrición - GC17, Instituto Maimónides de Investigación Biomédica de Córdoba, Hospital Universitario Reina Sofía, CIBERFES, Avda. Menéndez Pidal s/n, 14004, Córdoba, Spain

    Bárbara Torrecillas-Baena, María Ángeles Gálvez-Moreno, José Manuel Quesada-Gómez & Antonio Casado-Díaz

  2. Dep. Bioquímica y Biología Molecular, Campus Rabanales C6-1-E17, Campus de Excelencia Internacional Agroalimentario (ceiA3), Universidad de Córdoba, CIBERFES, 14071, Córdoba, Spain

    Gabriel Dorado

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BTB, JMQG and ACD designed the paper; BTB and ACD searched bibliography; BTB, GD and ACD wrote the manuscript; BTB, MAGM, JMQG, GD and ACD critically revised the content.

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Torrecillas-Baena, B., Gálvez-Moreno, M.Á., Quesada-Gómez, J.M. et al. Influence of Dipeptidyl Peptidase-4 (DPP4) on Mesenchymal Stem-Cell (MSC) Biology: Implications for Regenerative Medicine – Review. Stem Cell Rev and Rep 18, 56–76 (2022). https://doi.org/10.1007/s12015-021-10285-w

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