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Differential reduction of reactive oxygen species by human tissue-specific mesenchymal stem cells from different donors under oxidative stress

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Abstract

Clinical trials using human Mesenchymal Stem Cells (MSCs) have shown promising results in the treatment of various diseases. Different tissue sources, such as bone marrow, adipose tissue, dental pulp and umbilical cord, are being routinely used in regenerative medicine. MSCs are known to reduce increased oxidative stress levels in pathophysiological conditions. Differences in the ability of MSCs from different donors and tissues to ameliorate oxidative damage have not been reported yet. In this study, for the first time, we investigated the differences in the reactive oxygen species (ROS) reduction abilities of tissue-specific MSCs to mitigate cellular damage in oxidative stress. Hepatic Stellate cells (LX-2) and cardiomyocytes were treated with Antimycin A (AMA) to induce oxidative stress and tissue specific MSCs were co-cultured to study the reduction in ROS levels. We found that both donor’s age and source of tissue affected the ability of MSCs to reduce increased ROS levels in damaged cells. In addition, the abilities of same MSCs differed in LX-2 and cardiomyocytes in terms of magnitude of reduction of ROS, suggesting that the type of recipient cells should be kept in consideration when using MSCs in regenerative medicine for treatment purposes.

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Abbreviations

AD,:

adipose

AMA,:

Antimycin A

AU,:

arbitrary units

BM,:

bone marrow

DP,:

dental pulp

MFI,:

mean fluorescence intensity

MSC,:

mesenchymal stem cell

ROS,:

reactive oxygen species

References

  • Ahmad T, Mukherjee S, Pattnaik B, Kumar M, Singh S, Kumar M, Rehman R, Tiwari B K, Jha K A, Barhanpurkar A P, Wani M R, Roy S S, Mabalirajan U, Ghosh B and Agrawal A 2014 Miro1 regulates intercellular mitochondrial transport & enhances mesenchymal stem cell rescue efficacy. Embo J. 33 994–1010

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bataller R and Lemon S M 2012 Fueling fibrosis in chronic hepatitis C. Proc. Natl. Acad Sci USA 109 14293–14294

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Beane O S, Fonseca V C, Cooper L, Koren G and Darling E M 2014. Impact of aging on the regenerative properties of bone marrow-, muscle-, and adipose-derived mesenchymal stem/stromal cells. PLoS One 9 e115963

    Article  PubMed  PubMed Central  Google Scholar 

  • Bruna F, Contador D, Conget P, Erranz B, Sossa C L and Arango-Rodriguez M L 2016 Regenerative potential of mesenchymal stromal cells: age-related changes. Stem Cells Int. 2016 1461648

    Article  PubMed  PubMed Central  Google Scholar 

  • Bruno S, Grange C, Deregibus M C, Calogero R A, Saviozzi S, Collino F, Morando L, Busca A, Falda M, Bussolati B, Tetta C and Camussi G 2009 Mesenchymal stem cell-derived microvesicles protect against acute tubular injury. J. Am. Soc. Nephrol. 20 1053–1067

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Caicedo A, Fritz V, Brondello J M, Ayala M, Dennemont I, Abdellaoui N, Fraipont F, Moisan A, Prouteau C A, Boukhaddaoui H, Jorgensen C and Vignais, M L 2015 MitoCeption as a new tool to assess the effects of mesenchymal stem/stromal cell mitochondria on cancer cell metabolism and function. Sci. Rep. 5 9073

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Caplan A I and Dennis J E 2006 Mesenchymal stem cells as trophic mediators. J. Cell. Biochem. 98 1076–1084

    Article  CAS  PubMed  Google Scholar 

  • Chen J Y, Mou X Z, Du X C and Xiang C 2015 Comparative analysis of biological characteristics of adult mesenchymal stem cells with different tissue origins. Asian Pac. J. Trop. Med. 8 739–746

    Article  PubMed  Google Scholar 

  • Cho K A, Woo S Y, Seoh J Y, Han H S and Ryu K H 2012 Mesenchymal stem cells restore CCl4-induced liver injury by an antioxidative process. Cell Biol. Int. 36 1267–1274

    Article  CAS  PubMed  Google Scholar 

  • Collins E, Gu F, Qi M, Molano I, Ruiz P, Sun L and Gilkeson G S 2014 Differential efficacy of human mesenchymal stem cells based on source of origin. J. Immunol. 193 4381–4390

    Article  CAS  PubMed Central  Google Scholar 

  • Dutta D, Xu J, Kim J S, Dunn W A and Leeuwenburgh C 2013 Upregulated autophagy protects cardiomyocytes from oxidative stress-induced toxicity. Autophagy 9 328–344

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Griendling K K and FitzGerald G A 2003 Oxidative stress and cardiovascular injury: Part I: basic mechanisms and in vivo monitoring of ROS. Circulation 108 1912–1916

    Article  PubMed  Google Scholar 

  • Islam M N, Das S R, Emin M T, Wei M, Sun L, Westphalen K, Rowlands D J, Quadri S K, Bhattacharya S and Bhattacharya J 2012 Mitochondrial transfer from bone-marrow-derived stromal cells to pulmonary alveoli protects against acute lung injury. Nat. Med. 18 759–765

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jin H J, Bae Y K, Kim M, Kwon S J, Jeon H B, Choi S J, Kim S W, Yang Y S, Oh W and Chang, J W 2013 Comparative analysis of human mesenchymal stem cells from bone marrow, adipose tissue, and umbilical cord blood as sources of cell therapy. Int. J. Mol. Sci. 14 17986–18001

  • Kakkar A, Mohanty S, Bhargava B and Airan B 2015 Role of human cardiac biopsy derived conditioned media in modulating bone marrow derived mesenchymal stem cells toward cardiomyocyte-like cells. J. Pract. Cardiovasc. Sci. 1 150–155

  • Kawano Y, Ohta M, Iwashita Y, Komori Y, Inomata M and Kitano S 2014 Effects of the dihydrolipoyl histidinate zinc complex against carbon tetrachloride-induced hepatic fibrosis in rats. Surg. Today 44 1744–1750

    Article  CAS  PubMed  Google Scholar 

  • Kern S, Eichler H, Stoeve J, Kluter H and Bieback K 2006 Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells 24 1294–1301

    Article  CAS  PubMed  Google Scholar 

  • Khatri R, Krishnan S, Roy S, Chattopadhyay S, Kumar V and Mukhopadhyay A 2016 Reactive oxygen species limit the ability of bone marrow stromal cells to support hematopoietic reconstitution in aging mice. Stem Cells Dev. 25 948–958

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • King M A and Radicchi-Mastroianni M A 2002 Antimycin A-induced apoptosis of HL-60 cells. Cytometry. 49 106–112

    Article  CAS  PubMed  Google Scholar 

  • Koyanagi M, Brandes R P, Haendeler J, Zeiher A M and Dimmeler S 2005 Cell-to-cell connection of endothelial progenitor cells with cardiac myocytes by nanotubes: a novel mechanism for cell fate changes. Circ. Res. 96 1039–1041

    Article  CAS  PubMed  Google Scholar 

  • Li C Y, Wu X Y, Tong J B, Yang X X, Zhao J L, Zheng Q F, Zhao G B and Ma Z J 2015 Comparative analysis of human mesenchymal stem cells from bone marrow and adipose tissue under xeno-free conditions for cell therapy. Stem Cell Res. Ther. 6 55

    Article  PubMed  PubMed Central  Google Scholar 

  • Li J, Li D, Liu X, Tang S and Wei F 2012 Human umbilical cord mesenchymal stem cells reduce systemic inflammation and attenuate LPS-induced acute lung injury in rats. J. Inflamm. (Lond.) 9 33

    Article  PubMed Central  Google Scholar 

  • Liang X, Ding Y, Zhang Y, Tse H F and Lian Q 2014 Paracrine mechanisms of mesenchymal stem cell-based therapy: current status and perspectives. Cell Transpl. 23 1045–1059

  • Liu H, McTaggart S J, Johnson D W and Gobe G C 2012 Original article anti-oxidant pathways are stimulated by mesenchymal stromal cells in renal repair after ischemic injury. Cytotherapy 14 162–172

    Article  CAS  PubMed  Google Scholar 

  • Maumus M, Jorgensen C and Noel D 2013 Mesenchymal stem cells in regenerative medicine applied to rheumatic diseases: role of secretome and exosomes. Biochimie 95 2229–2234

    Article  CAS  PubMed  Google Scholar 

  • McCully J D, Cowan D B, Pacak C A, Toumpoulis I K, Dayalan H and Levitsky S 2009 Injection of isolated mitochondria during early reperfusion for cardioprotection. Am. J. Physiol. Heart Circ. Physiol. 296 H94–H105

    Article  CAS  PubMed  Google Scholar 

  • Mohanty S, Bose S, Jain K G, Bhargava B and Airan B 2013 TGFbeta1 contributes to cardiomyogenic-like differentiation of human bone marrow mesenchymal stem cells. Int. J. Cardiol. 163 93–99

    Article  PubMed  Google Scholar 

  • Nakamura T, Kazama T, Nagaoka Y, Inamo Y, Mugishima H, Takahashi S and Matsumoto T 2015 Influence of donor age and passage number on angiogenic activity in human adipose-derived stem cell-conditioned media. J. Stem Cell Res. Ther. 5 307

    Google Scholar 

  • Nandy S B, Mohanty S, Singh M, Behari M and Airan B 2014 Fibroblast Growth Factor-2 alone as an efficient inducer for differentiation of human bone marrow mesenchymal stem cells into dopaminergic neurons. J. Biomed. Sci. 21, 83

    Article  PubMed Central  Google Scholar 

  • Ohkouchi S, Block G J, Katsha A M, Kanehira M, Ebina M, Kikuchi T, Saijo Y, Nukiwa T, Prockop D J 2012 Mesenchymal stromal cells protect cancer cells from ROS-induced apoptosis and enhance the Warburg effect by secreting STC1. Mol. Ther. 20 417–423

    Article  CAS  PubMed  Google Scholar 

  • Park C W, Kim K S, Bae S, Son H K, Myung P K, Hong H J and Kim H 2009 Cytokine secretion profiling of human mesenchymal stem cells by antibody array. Int. J. Stem Cells 2 59–68

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Phinney D G, Di Giuseppe M, Njah J, Sala E, Shiva S, St Croix C M, Stolz D B, Watkins S C, Di Y P, Leikauf G D, Kolls J, Riches D W, Deiuliis G, Kaminski N, Boregowda S V, McKenna D H, Ortiz L A 2015 Mesenchymal stem cells use extracellular vesicles to outsource mitophagy and shuttle microRNAs. Nat. Commun. 6 8472

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pires A O, Mendes-Pinheiro B, Teixeira F G, Anjo S I, Ribeiro-Samy S, Gomes E D and Salgado A J 2016 Unveiling the differences of secretome of human bone marrow mesenchymal stem cells, adipose tissue-derived stem cells, and human umbilical cord perivascular cells: a proteomic analysis. Stem Cells Dev. 25 1073–1083

  • Poli G 2000 Pathogenesis of liver fibrosis: role of oxidative stress. Mol. Asp. Med. 21 49–98

  • Proell V, Carmona-Cuenca I, Murillo M M, Huber H, Fabregat I and Mikulits W 2007 TGF-beta dependent regulation of oxygen radicals during transdifferentiation of activated hepatic stellate cells to myofibroblastoid cells. Comp. Hepatol. 6 1–12

    Article  PubMed  PubMed Central  Google Scholar 

  • R Development Core Team 2010 R: a language and environment for statistical computing (R Foundation for Statistical Computing)

  • Ranganath S H, Levy O, Inamdar M S and Karp J M 2012 Harnessing the mesenchymal stem cell secretome for the treatment of cardiovascular disease. Cell Stem Cell 10 244–258

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Raposo G and Stoorvogel W 2013 Extracellular vesicles: exosomes, microvesicles, and friends. J Cell Biol. 200 373–383

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We would like to thank the Indian Council of Medical Research (ICMR) (Grant No. I-899) and Department of Biotechnology for providing funds and fellowship for conducting this work. We also thank Dr M Mani Sankar for providing inputs during scientific discussions.

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Correspondence to Sujata Mohanty.

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Corresponding editor: Geeta Vemuganti

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Paliwal, S., Kakkar, A., Sharma, R. et al. Differential reduction of reactive oxygen species by human tissue-specific mesenchymal stem cells from different donors under oxidative stress. J Biosci 42, 373–382 (2017). https://doi.org/10.1007/s12038-017-9691-8

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  • DOI: https://doi.org/10.1007/s12038-017-9691-8

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