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Perspectives of purinergic signaling in stem cell differentiation and tissue regeneration

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Abstract

Replacement of lost or dysfunctional tissues by stem cells has recently raised many investigations on therapeutic applications. Purinergic signaling has been shown to regulate proliferation, differentiation, cell death, and successful engraftment of stem cells originated from diverse origins. Adenosine triphosphate release occurs in a controlled way by exocytosis, transporters, and lysosomes or in large amounts from damaged cells, which is then subsequently degraded into adenosine. Paracrine and autocrine mechanisms induced by immune responses present critical factors for the success of stem cell therapy. While P1 receptors generally exert beneficial effects including anti-inflammatory activity, P2 receptor-mediated actions depend on the subtype of stimulated receptors and localization of tissue repair. Pro-inflammatory actions and excitatory tissue damages mainly result from P2X7 receptor activation, while other purinergic receptor subtypes participate in proliferation and differentiation, thereby providing adequate niches for stem cell engraftment and novel mechanisms for cell therapy and endogenous tissue repair. Therapeutic applications based on regulation of purinergic signaling are foreseen for kidney and heart muscle regeneration, Clara-like cell replacement for pulmonary and bronchial epithelial cells as well as for induction of neurogenesis in case of neurodegenerative diseases.

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Acknowledgments

HU acknowledges grant support from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) and CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico), Brazil, project no. 2006/61285-9. TG, PDN, and CL are supported by fellowships from FAPESP. ARC, MMP, and IC are grateful for fellowships from CNPq. Grant support by FAPERGS/CNPq - PRONEX, Brazil, is also acknowledged.

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  1. Departamento de Bioquímica , Instituto de Química, Universidade São Paulo, Av. Prof. Lineu Prestes, 748-Bloco 8S/Room 0858, CEP: 05508-900, São Paulo, SP, Brazil

    Talita Glaser, Micheli Mainardi Pillat & Henning Ulrich

  2. Departamento de Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil

    Angélica Regina Cappellari & Ana Maria Oliveira Battastini

  3. Departamento de Ciências Básicas da Saúde, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS, Brazil

    Isabele Cristiana Iser & Márcia Rosângela Wink

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  1. Talita Glaser
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Glaser, T., Cappellari, A.R., Pillat, M.M. et al. Perspectives of purinergic signaling in stem cell differentiation and tissue regeneration. Purinergic Signalling 8, 523–537 (2012). https://doi.org/10.1007/s11302-011-9282-3

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