Journal of Biosciences

, Volume 42, Issue 3, pp 373–382 | Cite as

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

  • Swati Paliwal
  • Anupama Kakkar
  • Rinkey Sharma
  • Balram Airan
  • Sujata MohantyEmail author
Brief communication


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.


Oxidative stress reactive oxygen species tissue-specific mesenchymal stem cells 





Antimycin A


arbitrary units


bone marrow


dental pulp


mean fluorescence intensity


mesenchymal stem cell


reactive oxygen species



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.

Supplementary material

12038_2017_9691_MOESM1_ESM.pdf (44 kb)
Supplementary material 1 (PDF 43 kb)


  1. 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. 33 994–1010PubMedPubMedCentralGoogle Scholar
  2. Bataller R and Lemon S M 2012 Fueling fibrosis in chronic hepatitis C. Proc. Natl. Acad Sci USA 109 14293–14294CrossRefPubMedPubMedCentralGoogle Scholar
  3. 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 e115963CrossRefPubMedPubMedCentralGoogle Scholar
  4. 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 1461648CrossRefPubMedPubMedCentralGoogle Scholar
  5. 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 1053–1067CrossRefPubMedPubMedCentralGoogle Scholar
  6. 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 9073CrossRefPubMedPubMedCentralGoogle Scholar
  7. Caplan A I and Dennis J E 2006 Mesenchymal stem cells as trophic mediators. J. Cell. Biochem. 98 1076–1084CrossRefPubMedGoogle Scholar
  8. 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. 8 739–746CrossRefPubMedGoogle Scholar
  9. 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 1267–1274CrossRefPubMedGoogle Scholar
  10. 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 4381–4390CrossRefPubMedCentralGoogle Scholar
  11. Dutta D, Xu J, Kim J S, Dunn W A and Leeuwenburgh C 2013 Upregulated autophagy protects cardiomyocytes from oxidative stress-induced toxicity. Autophagy 9 328–344CrossRefPubMedPubMedCentralGoogle Scholar
  12. 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 1912–1916CrossRefPubMedGoogle Scholar
  13. 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. 18 759–765CrossRefPubMedPubMedCentralGoogle Scholar
  14. 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 17986–18001Google Scholar
  15. 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. 1 150–155Google Scholar
  16. 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 1744–1750CrossRefPubMedGoogle Scholar
  17. 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 1294–1301CrossRefPubMedGoogle Scholar
  18. 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. 25 948–958CrossRefPubMedPubMedCentralGoogle Scholar
  19. King M A and Radicchi-Mastroianni M A 2002 Antimycin A-induced apoptosis of HL-60 cells. Cytometry. 49 106–112CrossRefPubMedGoogle Scholar
  20. 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 1039–1041CrossRefPubMedGoogle Scholar
  21. 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 55CrossRefPubMedPubMedCentralGoogle Scholar
  22. 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 33CrossRefPubMedCentralGoogle Scholar
  23. 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 1045–1059Google Scholar
  24. 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 14 162–172CrossRefPubMedGoogle Scholar
  25. 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 2229–2234CrossRefPubMedGoogle Scholar
  26. 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–H105CrossRefPubMedGoogle Scholar
  27. 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 93–99CrossRefPubMedGoogle Scholar
  28. 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 307Google Scholar
  29. 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, 83CrossRefPubMedCentralGoogle Scholar
  30. 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. 20 417–423CrossRefPubMedGoogle Scholar
  31. 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 59–68CrossRefPubMedPubMedCentralGoogle Scholar
  32. 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 8472CrossRefPubMedPubMedCentralGoogle Scholar
  33. 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 1073–1083Google Scholar
  34. Poli G 2000 Pathogenesis of liver fibrosis: role of oxidative stress. Mol. Asp. Med. 21 49–98Google Scholar
  35. 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 1–12CrossRefPubMedPubMedCentralGoogle Scholar
  36. R Development Core Team 2010 R: a language and environment for statistical computing (R Foundation for Statistical Computing)Google Scholar
  37. 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 10 244–258CrossRefPubMedPubMedCentralGoogle Scholar
  38. Raposo G and Stoorvogel W 2013 Extracellular vesicles: exosomes, microvesicles, and friends. J Cell Biol. 200 373–383CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Indian Academy of Sciences 2017

Authors and Affiliations

  • Swati Paliwal
    • 1
  • Anupama Kakkar
    • 1
  • Rinkey Sharma
    • 1
  • Balram Airan
    • 2
  • Sujata Mohanty
    • 1
    Email author
  1. 1.Stem Cell FacilityAll India Institute of Medical SciencesNew DelhiIndia
  2. 2.Department of Cardio Thoracic Vascular SurgeryAll India Institute of Medical SciencesNew DelhiIndia

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