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Editorial Improving the Therapeutic Ability of Mesenchymal Stem/Stromal Cells for the Treatment of Conditions Influenced by Immune Cells Lindolfo da Silva Meirelles , 1 Marcela F. Bolontrade, 2 Melissa Medeiros Markoski , 3 Bruno Dallagiovanna, 4 and Laura Alaniz 5 1 PPGBioSaúde, Lutheran University of Brazil, Canoas, Brazil 2 IMTIB-CONICET-IUHI-HIBA, Buenos Aires, Argentina 3 Federal University of Health Sciences of Porto Alegre, Porto Alegre, Brazil 4 Carlos Chagas InstituteFiocruz Paraná, Curitiba, Brazil 5 CIT NOBACONICET-UNNOBA, Junín, Argentina Correspondence should be addressed to Lindolfo da Silva Meirelles; [email protected] Received 26 November 2019; Accepted 27 November 2019; Published 6 December 2019 Copyright © 2019 Lindolfo da Silva Meirelles et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Mesenchymal stem/stromal cells (MSCs) have been initially described decades ago as broblastic precursors that could be isolated from the bone marrow and establish cultures of broblastic cells. These broblastic cells were shown to support hematopoiesis in vitro, which is a characteristic of stromal cells, and, later, to give rise to mature mesenchymal cells such as bone, cartilage, and fat cells when cultured under appropriate conditions. The proposition that a mesenchymal stem cell exists in postnatal bone marrow and other tissues as blood vessel-associated cells provided further momentum to research on these cells, as well as divergences on how to call them. The impetus of using MSCs to replace cells lost in various types of conditions eventually decreased, as the ther- apeutic benets provided by these cells were found to be mostly due to the secretion of paracrine signaling molecules, which can be carried by extracellular vesicles. In the mean- time, MSCs were found to modulate the behavior of immune cells by means of secretion of molecules that could, in dier- ent scenarios, inhibit the activation of T cells that promote adaptive immune responses. Subsequently, the eects of MSCs on other cells of the immune system were also described. Today, a number of clinical trials using MSCs to treat conditions inuenced by immune cells are under way. While preclinical data indicates that MSCs have important immunomodulatory properties, further studies are still in progress to increase the knowledge on the dierences regard- ing the action of MSCs on immune cells according to their tissue of origin, on how MSCs exert their eects on the dier- ent types of immune cells, and on ways to improve the out- come of conditions inuenced by immune cells when treated using MSCS. This special issue was open to basic research manuscripts and reviews that approached ways to improve the therapeutic ability of MSCs for the treatment of conditions inuenced by immune cells. Accordingly, two basic research papers on the interactions between MSCs and immune cells in skin wound models and three reviews on aspects of the relations between these cells were accepted. S. Xiao et al. showed that forced expression of interleukin-10, an anti-inammatory cytokine, in human amnion-derived MSCs improves the healing of full-thickness skin wounds in mice by reducing inammation and excessive extracellular matrix deposition while improv- ing angiogenesis. He and his colleagues focused on the eects of exosomes, a type of extracellular vesicle, produced by MSCs isolated from human bone marrow on the polarization of macrophages in full-thickness skin wounds of mice. Con- sequently, X. He et al. found that microRNA-223 present in these exosomes contribute to a proregenerative M2 polariza- tion in macrophages. B. S. Guerrouahen et al. reviewed mechanisms underlying communication of MSCs with Hindawi Stem Cells International Volume 2019, Article ID 6820395, 2 pages https://doi.org/10.1155/2019/6820395

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Page 1: Improving the Therapeutic Ability of Mesenchymal Stem

EditorialImproving the Therapeutic Ability of Mesenchymal Stem/StromalCells for the Treatment of Conditions Influenced by Immune Cells

Lindolfo da Silva Meirelles ,1 Marcela F. Bolontrade,2 Melissa Medeiros Markoski ,3

Bruno Dallagiovanna,4 and Laura Alaniz 5

1PPGBioSaúde, Lutheran University of Brazil, Canoas, Brazil2IMTIB-CONICET-IUHI-HIBA, Buenos Aires, Argentina3Federal University of Health Sciences of Porto Alegre, Porto Alegre, Brazil4Carlos Chagas Institute–Fiocruz Paraná, Curitiba, Brazil5CIT NOBA–CONICET-UNNOBA, Junín, Argentina

Correspondence should be addressed to Lindolfo da Silva Meirelles; [email protected]

Received 26 November 2019; Accepted 27 November 2019; Published 6 December 2019

Copyright © 2019 Lindolfo da Silva Meirelles et al. This is an open access article distributed under the Creative CommonsAttribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original workis properly cited.

Mesenchymal stem/stromal cells (MSCs) have been initiallydescribed decades ago as fibroblastic precursors that couldbe isolated from the bone marrow and establish cultures offibroblastic cells. These fibroblastic cells were shown tosupport hematopoiesis in vitro, which is a characteristic ofstromal cells, and, later, to give rise to mature mesenchymalcells such as bone, cartilage, and fat cells when cultured underappropriate conditions. The proposition that a mesenchymalstem cell exists in postnatal bone marrow and other tissues asblood vessel-associated cells provided further momentum toresearch on these cells, as well as divergences on how to callthem. The impetus of using MSCs to replace cells lost invarious types of conditions eventually decreased, as the ther-apeutic benefits provided by these cells were found to bemostly due to the secretion of paracrine signaling molecules,which can be carried by extracellular vesicles. In the mean-time, MSCs were found to modulate the behavior of immunecells by means of secretion of molecules that could, in differ-ent scenarios, inhibit the activation of T cells that promoteadaptive immune responses. Subsequently, the effects ofMSCs on other cells of the immune system were alsodescribed. Today, a number of clinical trials using MSCs totreat conditions influenced by immune cells are under way.While preclinical data indicates that MSCs have importantimmunomodulatory properties, further studies are still in

progress to increase the knowledge on the differences regard-ing the action of MSCs on immune cells according to theirtissue of origin, on howMSCs exert their effects on the differ-ent types of immune cells, and on ways to improve the out-come of conditions influenced by immune cells whentreated using MSCS.

This special issue was open to basic research manuscriptsand reviews that approached ways to improve the therapeuticability of MSCs for the treatment of conditions influenced byimmune cells. Accordingly, two basic research papers on theinteractions between MSCs and immune cells in skin woundmodels and three reviews on aspects of the relations betweenthese cells were accepted. S. Xiao et al. showed that forcedexpression of interleukin-10, an anti-inflammatory cytokine,in human amnion-derived MSCs improves the healing offull-thickness skin wounds in mice by reducing inflammationand excessive extracellular matrix deposition while improv-ing angiogenesis. He and his colleagues focused on the effectsof exosomes, a type of extracellular vesicle, produced byMSCs isolated from human bone marrow on the polarizationof macrophages in full-thickness skin wounds of mice. Con-sequently, X. He et al. found that microRNA-223 present inthese exosomes contribute to a proregenerative M2 polariza-tion in macrophages. B. S. Guerrouahen et al. reviewedmechanisms underlying communication of MSCs with

HindawiStem Cells InternationalVolume 2019, Article ID 6820395, 2 pageshttps://doi.org/10.1155/2019/6820395

Page 2: Improving the Therapeutic Ability of Mesenchymal Stem

immune cells and discussed clinical applications of MSCs indiseases mediated by immune cells. F.V. Paladino et al.reviewed the immunomodulatory properties of Wharton’sjelly-derived MSCs. Finally, Z. Fábián discussed the effectsof hypoxia on the immunomodulatory properties of the bonemarrow. This group of articles provides a contribution tobetter understand and, consequently, improve the therapeu-tic properties of MSCs for the treatment of conditions influ-enced by the immune system.

Conflicts of Interest

The editors declare that they have no conflicts of interestregarding the publication of this special issue.

Acknowledgments

We thank Ms. Princy Arputharaj for overtaking the editorialtasks in the process of this special issue.

Lindolfo da Silva MeirellesMarcela F. Bolontrade

Melissa Medeiros MarkoskiBruno Dallagiovanna

Laura Alaniz

2 Stem Cells International

Page 3: Improving the Therapeutic Ability of Mesenchymal Stem

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