, Volume 68, Issue 5, pp 2061–2073 | Cite as

Generation and characterization of human cardiac resident and non-resident mesenchymal stem cell

  • Baskar Subramani
  • Sellamuthu Subbannagounder
  • Sekar Palanivel
  • Chithra Ramanathanpullai
  • Sivakumar Sivalingam
  • Azhari Yakub
  • Manjunath SadanandaRao
  • Arivudainambi Seenichamy
  • Ashok Kumar Pandurangan
  • Jun Jie Tan
  • Rajesh RamasamyEmail author
Original Article


Despite the surgical and other insertional interventions, the complete recuperation of myocardial disorders is still elusive due to the insufficiency of functioning myocardiocytes. Thus, the use of stem cells to regenerate the affected region of heart becomes a prime important. In line with this human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) have gained considerable interest due to their potential use for mesodermal cell based replacement therapy and tissue engineering. Since MSCs are harvested from various organs and anatomical locations of same organism, thus the cardiac regenerative potential of human cardiac-derived MSCs (hC-MSCs) and human umbilical cord Wharton’s Jelly derived MSC (hUC-MSCs) were tested concurrently. At in vitro culture, both hUC-MSCs and hC-MSCs assumed spindle shape morphology with expression of typical MSC markers namely CD105, CD73, CD90 and CD44. Although, hUC-MSCs and hC-MSCs are identical in term of morphology and immunophenotype, yet hUC-MSCs harbored a higher cell growth as compared to the hC-MSCs. The inherent cardiac regenerative potential of both cells were further investigated with mRNA expression of ion channels. The RT-PCR results demonstrated that both MSCs were expressing a notable level of delayed rectifier-like K+ current (I KDR ) ion channel, yet the relative expression level was considerably varied between hUC-MSCs and hC-MSCs that Kv1.1(39 ± 0.6 vs 31 ± 0.8), Kv2.1 (6 ± 0.2 vs 21 ± 0.12), Kv1.5 (7.4 ± 0.1 vs 6.8 ± 0.06) and Kv7.3 (27 ± 0.8 vs 13.8 ± 0.6). Similarly, the Ca2+-activated K+ current (I KCa ) channel encoding gene, transient outward K+ current (I to ) and TTX-sensitive transient inward sodium current (I Na.TTX ) encoding gene (Kv4.2, Kv4.3 and hNE-Na) expressions were detected in both groups as well. Despite the morphological and phenotypical similarity, the present study also confirms the existence of multiple functional ion channel currents IKDR, IKCa, Ito, and INa.TTX in undifferentiated hUC-MSCs as of hC-MSCs. Thus, the hUC-MSCs can be exploited as a potential candidate for future cardiac regeneration.


Mesenchymal stem cell Electrophysiology Cardiac resident stem cell and umbilical cord stem cell 



Mesenchymal stem cells


Bone marrow-derived MSCs


Cardiac stem cells


Human cardiac MSC


Human umbilical cord derived MSCs


Compliance with ethical standards

Conflict of interest

The authors express no conflicts of interest towards the publication of this paper.


  1. Bai X, Ma J, Pan Z, Song YH, Freyberg S, Yan Y, Vykoukal D, Alt E (2007) Electrophysiological properties of human adipose tissue-derived stem cells. Am J Physiol Cell Physiol 293:C1539–C1550CrossRefGoogle Scholar
  2. Bearzi C, Leri A, Lo Monaco F, Rota M, Gonzalez A, Hosoda T, Pepe M, Qanud K, Ojaimi C, Bardelli S, D’Amario D, D’Alessandro DA, Michler RE, Dimmeler S, Zeiher AM, Urbanek K, Hintze TH, Kajstura J, Anversa P (2009) Identification of a coronary vascular progenitor cell in the human heart. Proc Natl Acad Sci USA 15:15885–15890CrossRefGoogle Scholar
  3. Bieback K, Kern S, Klüter H, Eichler H (2004) Critical parameters for the isolation of mesenchymal stem cells from umbilical cord blood. Stem Cells 22:625–634CrossRefGoogle Scholar
  4. Can A, Balci D (2011) Isolation, culture, and characterization of human umbilical cord stroma-derived mesenchymal stem cells. Methods Mol Biol 698:51–62CrossRefGoogle Scholar
  5. Caplan AI (2007) Adult mesenchymal stem cells for tissue engineering versus regenerative medicine. J Cell Physiol 213:341–347CrossRefGoogle Scholar
  6. Cesare P, Moriondo A, Vellani V, McNaughton PA (1999) Ion channels gated by heat. Proc Natl Acad Sci USA 96:7658–7663CrossRefGoogle Scholar
  7. Chen LX, Zhu LY, Jacob TJ, Wang LW (2007) Roles of volume-activated Cl- currents and regulatory volume decrease in the cell cycle and proliferation in nasopharyngeal carcinoma cells. Cell Prolif 40:253–267CrossRefGoogle Scholar
  8. Chong JJ, Chandrakanthan V, Xaymardan M, Asli NS, Li J, Ahmed I, Heffernan C, Menon MK, Scarlett CJ, Rashidianfar A, Biben C, Zoellner H, Colvin EK, Pimanda JE, Biankin AV, Zhou B, Pu WT, Prall OW, Harvey RP (2011) Adult cardiac-resident MSC-like stem cells with a proepicardial origin. Cell Stem Cell 2:527–540CrossRefGoogle Scholar
  9. Deans RJ, Moseley AB (2000) Mesenchymal stem cells: biology and potential clinical uses. Exp Hematol 28:875–884CrossRefGoogle Scholar
  10. Feldmann RE Jr, Bieback K, Maurer MH, Kalenka A, Bürgers HF, Gross B, Hunzinger C, Klüter H, Kuschinsky W, Eichler H (2005) Stem cell proteomes: a profile of human mesenchymal stem cells derived from umbilical cord blood. Electrophoresis 26:2749–2758CrossRefGoogle Scholar
  11. Forbes SJ, Vig P, Poulsom R, Wright NA, Alison MR (2002) Adult stem cell plasticity: new pathways of tissue regeneration become visible. Clin Sci (Lond) 103:355–369CrossRefGoogle Scholar
  12. Fuentes T, Kearns-Jonker M (2013) Endogenous cardiac stem cells for the treatment of heart failure. Stem Cells Cloning 25:1–12Google Scholar
  13. Gallina C, Turinetto V, Giachino C (2015) A new paradigm in cardiac regeneration: the mesenchymal stem cell secretome. Stem Cells Int 2015:765846CrossRefGoogle Scholar
  14. Goodwin HS, Bicknese AR, Chien SN, Bogucki BD, Quinn CO, Wall DA (2001) Multilineage differentiation activity by cells isolated from umbilical cord blood: expression of bone, fat, and neural markers. Biol Blood Marrow Transplant 7:581–588CrossRefGoogle Scholar
  15. Hartmann I, Hollweck T, Haffner S, Krebs M, Meiser B, Reichart B, Eissner G (2010) Umbilical cord tissue-derived mesenchymal stem cells grow best under GMP-compliant culture conditions and maintain their phenotypic and functional properties. J Immunol Methods 15:80–89CrossRefGoogle Scholar
  16. He JQ, Vu DM, Hunt G, Chugh A, Bhatnagar A, Bolli R (2011) Human cardiac stem cells isolated from atrial appendages stably express c-kit. PLoS ONE 6:e27719CrossRefGoogle Scholar
  17. Heubach JF, Graf EM, Leutheuser J, Bock M, Balana B, Zahanich I, Christ T, Boxberger S, Wettwer E, Ravens U (2004) Electrophysiological properties of human mesenchymal stem cells. J Physiol 1:659–672CrossRefGoogle Scholar
  18. Hoogduijn MJ, Crop MJ, Peeters AM, Van Osch GJ, Balk AH, Ijzermans JN, Weimar W, Baan CC (2007) Human heart, spleen, and perirenal fat-derived mesenchymal stem cells have immunomodulatory capacities. Stem Cells Dev 16:597–604CrossRefGoogle Scholar
  19. Kazakov A, Meier T, Werner C, Hall R, Klemmer B, Körbel C, Lammert F, Maack C, Böhm M, Laufs U (2015) C-kit(+) resident cardiac stem cells improve left ventricular fibrosis in pressure overload. Stem Cell Res 15:700–711CrossRefGoogle Scholar
  20. Kinnaird T, Stabile E, Burnett MS, Shou M, Lee CW, Barr S, Fuchs S, Epstein SE (2004) Local delivery of marrow-derived stromal cells augments collateral perfusion through paracrine mechanisms. Circulation 30:1543–1549CrossRefGoogle Scholar
  21. Li GR, Sun H, Deng X, Lau CP (2005) Characterization of ionic currents in human mesenchymal stem cells from bone marrow. Stem Cells 23:371–382CrossRefGoogle Scholar
  22. Mazhari R, Hare JM (2007) Mechanisms of action of mesenchymal stem cells in cardiac repair: potential influences on the cardiac stem cell niche. Nat Clin Pract Cardiovasc Med 1:S21–S26CrossRefGoogle Scholar
  23. Mc Elreavey KD, Irvine AI, Ennis KT, McLean WH (1991) Isolation, culture and characterisation of fibroblast-like cells derived from the Wharton’s jelly portion of human umbilical cord. Biochem Soc Trans 19:29SCrossRefGoogle Scholar
  24. Menasche P, Hagege AA, Vilquin JT, Desnos M, Abergel E, Pouzet B, Bel A, Sarateanu S, Scorsin M, Schwartz K, Bruneval P, Benbunan M, Marolleau JP, Duboc D (2003) Autologous skeletal myoblast transplantation for severe postinfarction left ventricular dysfunction. J Am Coll Cardiol 41:1078–1083CrossRefGoogle Scholar
  25. Mindaye ST, Surdo JL, Bauer SR, Alterman MA (2015) System-wide survey of proteomic responses of human bone marrow stromal cells (hBMSCs) to in vitro cultivation. Stem Cell Res 15:655–664CrossRefGoogle Scholar
  26. Miyahara Y, Nagaya N, Kataoka M, Yanagawa B, Tanaka K, Hao H, Ishino K, Ishida H, Shimizu T, Kangawa K, Sano S, Okano T, Kitamura S, Mori H (2006) Monolayered mesenchymal stem cells repair scarred myocardium after myocardial infarction. Nat Med 12:459–465CrossRefGoogle Scholar
  27. Mueller SM, Glowacki J (2001) Age-related decline in the osteogenic potential of human bone marrow cells cultured in three-dimensional collagen sponges. J Cell Biochem 82:583–590CrossRefGoogle Scholar
  28. Nilius B, Droogmans G (2001) Ion channels and their functional role in vascular endothelium. Physiol Rev 81:1415–1459Google Scholar
  29. Obradovic S, Rusović S, Balint B, Ristić-Andelkov A, Romanović R, Baskot B, Vojvodić D, Gligić B (2004) Autologous bone marrow-derived progenitor cell transplantation for myocardial regeneration after acute infarction. Vojnosanit Pregl 61:519–529CrossRefGoogle Scholar
  30. Orlic D, Kajstura J, Chimenti S, Jakoniuk I, Anderson SM, Li B, Pickel J, McKay R, Nadal-Ginard B, Bodine DM, Leri A, Anversa P (2001) Bone marrow cells regenerate infarcted myocardium. Nature 5:701–705CrossRefGoogle Scholar
  31. Pardo LA, Brüggemann A, Camacho J, Stühmer W (1998) Cell cycle-related changes in the conducting properties of r-eag K+ channels. J Cell Biol 143:767–775CrossRefGoogle Scholar
  32. Park KS, Jung KH, Kim SH, Kim KS, Choi MR, Kim Y, Chai YG (2007) Functional expression of ion channels in mesenchymal stem cells derived from umbilical cord vein. Stem Cells 25:2044–2052CrossRefGoogle Scholar
  33. Pereira WC, Khushnooma I, Madkaikar M, Ghosh K (2008) Reproducible methodology for the isolation of mesenchymal stem cells from human umbilical cord and its potential for cardiomyocyte generation. J Tissue Eng Regen Med 2:394–399CrossRefGoogle Scholar
  34. Peters NS (2005) Arrhythmias after cell transplantation for myocardial regeneration: natural history or result of the intervention? J Cardiovasc Electrophysiol 16:1255–1257CrossRefGoogle Scholar
  35. Ramasamy R, Tong CK, Seow HF, Vidyadaran S, Dazzi F (2008) The immunosuppressive effects of human bone marrow-derived mesenchymal stem cells target T cell proliferation but not its effector function. Cell Immunol 251:131–136CrossRefGoogle Scholar
  36. Rao MS, Mattson MP (2001) Stem cells and aging: expanding the possibilities. Mech Ageing Dev 31:713–734CrossRefGoogle Scholar
  37. Sanchez-Ramos J, Song S, Cardozo-Pelaez F, Hazzi C, Stedeford T, Willing A, Freeman TB, Saporta S, Janssen W, Patel N, Cooper DR, Sanberg PR (2000) Adult bone marrow stromal cells differentiate into neural cells in vitro. Exp Neurol 164:247–256CrossRefGoogle Scholar
  38. Santos ND, Mosqueira D, Sousa LM, Teixeira M, Filipe M, Resende TP, Araújo AF, Valente M, Almeida J, Martins JP, Santos JM, Bárcia RN, Cruz P, Cruz H, Pinto-do-Ó P (2014) Human umbilical cord tissue-derived mesenchymal stromal cells attenuate remodeling after myocardial infarction by proangiogenic, antiapoptotic, and endogenous cell-activation mechanisms. Stem Cell Res Ther 10:5CrossRefGoogle Scholar
  39. Shaer A, Azarpira N, Aghdaie MH, Esfandiari E (2014) Isolation and characterization of human mesenchymal stromal cells derived from placental decidua basalis; umbilical cord Wharton’s jelly and amniotic membrane. Pak J Med Sci 30:1022–1026Google Scholar
  40. Shake JG, Gruber PJ, Baumgartner WA, Senechal G, Meyers J, Redmond JM, Pittenger MF, Martin BJ (2002) Mesenchymal stem cell implantation in a swine myocardial infarct model: engraftment and functional effects. Ann Thorac Surg 73:1919–1925CrossRefGoogle Scholar
  41. Siminiak T, Kalawski R, Fiszer D, Jerzykowska O, Rzeźniczak J, Rozwadowska N, Kurpisz M (2004) Autologous skeletal myoblast transplantation for the treatment of postinfarction myocardial injury: phase I clinical study with 12 months of follow-up. Am Heart J 148:531–537CrossRefGoogle Scholar
  42. Takehara N, Tsutsumi Y, Tateishi K, Ogata T, Tanaka H, Ueyama T, Takahashi T, Takamatsu T, Fukushima M, Komeda M, Yamagishi M, Yaku H, Tabata Y, Matsubara H, Oh H (2008) Controlled delivery of basic fibroblast growth factor promotes human cardiosphere-derived cell engraftment to enhance cardiac repair for chronic myocardial infarction. J Am Coll Cardiol 52:1858–1865CrossRefGoogle Scholar
  43. Tong CK, Vellasamy S, Tan BC, Abdullah M, Vidyadaran S, Seow HF, Ramasamy R (2011) Generation of mesenchymal stem cell from human umbilical cord tissue using a combination enzymatic and mechanical disassociation method. Cell Biol Int 35:221–226CrossRefGoogle Scholar
  44. Vellasamy S, Sandrasaigaran P, Vidyadaran S, George E, Ramasamy R (2012) Isolation and characterization of mesenchymal stem cells derived from human placenta tissue. World J Stem Cells. 26:53–61CrossRefGoogle Scholar
  45. Von Zglinicki T, Martin-Ruiz CM (2005) Telomeres as biomarkers for ageing and age-related diseases. Curr Mol Med 5:197–203CrossRefGoogle Scholar
  46. Wang HS, Hung SC, Peng ST, Huang CC, Wei HM, Guo YJ, Fu YS, Lai MC, Chen CC (2004) Mesenchymal stem cells in the Wharton’s jelly of the human umbilical cord. Stem Cells 22:1330–1337CrossRefGoogle Scholar
  47. Weil BR, Canty JM Jr (2013) Stem cell stimulation of endogenous myocyte regeneration. Clin Sci (Lond) 125:109–119CrossRefGoogle Scholar
  48. Weiss ML, Medicetty S, Bledsoe AR, Rachakatla RS, Choi M, Merchav S, Luo Y, Rao MS, Velagaleti G, Troyer D (2006) Human umbilical cord matrix stem cells: preliminary characterization and effect of transplantation in a rodent model of Parkinson’s disease. Stem Cells 24:781–792CrossRefGoogle Scholar
  49. Zhang YM, Hartzell C, Narlow M, Dudley SC Jr (2002) Stem cell-derived cardiomyocytes demonstrate arrhythmic potential. Circulation 3:1294–1299CrossRefGoogle Scholar
  50. Zimmer T, Haufe V, Blechschmidt S (2014) Voltage-gated sodium channels in the mammalian heart. Glob Cardiol Sci Pract 31:449–463Google Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2016

Authors and Affiliations

  • Baskar Subramani
    • 1
    • 2
  • Sellamuthu Subbannagounder
    • 1
  • Sekar Palanivel
    • 3
  • Chithra Ramanathanpullai
    • 1
  • Sivakumar Sivalingam
    • 4
  • Azhari Yakub
    • 4
  • Manjunath SadanandaRao
    • 5
  • Arivudainambi Seenichamy
    • 6
  • Ashok Kumar Pandurangan
    • 7
  • Jun Jie Tan
    • 8
  • Rajesh Ramasamy
    • 9
    • 10
    Email author
  1. 1.Nichi-Asia Life Sdn Bhd.Petaling JayaMalaysia
  2. 2.Bharathiyar UniversityCoimbatoreIndia
  3. 3.Departments of ZoologyGovernment Arts College (Autonomous)SalemIndia
  4. 4.Cardiothoracic Surgery UnitNational Heart InstituteKuala LumpurMalaysia
  5. 5.Micro Therapeutic Research Labs Pvt. LtdChennaiIndia
  6. 6.Department of Veterinary Pathology and MicrobiologyUniversiti Putra MalaysiaSerdangMalaysia
  7. 7.Department of Pharmacology, Faculty of MedicineUniversity of MalayaKuala LumpurMalaysia
  8. 8.Regeneration Medicine Cluster, Advanced Medicine and Dental InstituteUniversiti Sains MalaysiaGeorge TownMalaysia
  9. 9.Stem Cell and Immunity Group, Immunology Laboratory Unit, Department Of Pathology, Faculty of Medicine and Health SciencesUniversiti Putra MalaysiaSerdangMalaysia
  10. 10.Stem Cell Research Laboratory, Genetic and Regenerative Medicine Research Center, Faculty of Medicine and Health SciencesUniversiti Putra MalaysiaSerdangMalaysia

Personalised recommendations