Skip to main content

Advertisement

SpringerLink
Log in

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

  • Original Article
  • Published:
Cytotechnology Aims and scope Submit manuscript

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

MSCs:

Mesenchymal stem cells

BM-MSCs:

Bone marrow-derived MSCs

CSC:

Cardiac stem cells

hC-MSC:

Human cardiac MSC

hUC-MSCs:

Human umbilical cord derived MSCs

References

  • 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–C1550

    Article  CAS  Google Scholar 

  • 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 15:15885–15890

    Article  Google Scholar 

  • Bieback K, Kern S, Klüter H, Eichler H (2004) Critical parameters for the isolation of mesenchymal stem cells from umbilical cord blood. Stem Cells 22:625–634

    Article  Google Scholar 

  • Can A, Balci D (2011) Isolation, culture, and characterization of human umbilical cord stroma-derived mesenchymal stem cells. Methods Mol Biol 698:51–62

    Article  CAS  Google Scholar 

  • Caplan AI (2007) Adult mesenchymal stem cells for tissue engineering versus regenerative medicine. J Cell Physiol 213:341–347

    Article  CAS  Google Scholar 

  • Cesare P, Moriondo A, Vellani V, McNaughton PA (1999) Ion channels gated by heat. Proc Natl Acad Sci USA 96:7658–7663

    Article  CAS  Google Scholar 

  • 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 40:253–267

    Article  CAS  Google Scholar 

  • 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 2:527–540

    Article  Google Scholar 

  • Deans RJ, Moseley AB (2000) Mesenchymal stem cells: biology and potential clinical uses. Exp Hematol 28:875–884

    Article  CAS  Google Scholar 

  • 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 26:2749–2758

    Article  CAS  Google Scholar 

  • 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) 103:355–369

    Article  CAS  Google Scholar 

  • Fuentes T, Kearns-Jonker M (2013) Endogenous cardiac stem cells for the treatment of heart failure. Stem Cells Cloning 25:1–12

    Google Scholar 

  • Gallina C, Turinetto V, Giachino C (2015) A new paradigm in cardiac regeneration: the mesenchymal stem cell secretome. Stem Cells Int 2015:765846

    Article  Google Scholar 

  • 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 7:581–588

    Article  CAS  Google Scholar 

  • 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 15:80–89

    Article  Google Scholar 

  • 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:e27719

    Article  CAS  Google Scholar 

  • 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 1:659–672

    Article  Google Scholar 

  • 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 16:597–604

    Article  CAS  Google Scholar 

  • https://clinicaltrials.gov/ct2/results?term=mesenchymal+stem+cells+AND+myocardial+infarction

  • 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 15:700–711

    Article  CAS  Google Scholar 

  • 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 30:1543–1549

    Article  Google Scholar 

  • Li GR, Sun H, Deng X, Lau CP (2005) Characterization of ionic currents in human mesenchymal stem cells from bone marrow. Stem Cells 23:371–382

    Article  CAS  Google Scholar 

  • 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–S26

    Article  Google Scholar 

  • 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 19:29S

    Article  CAS  Google Scholar 

  • 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 41:1078–1083

    Article  Google Scholar 

  • 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 15:655–664

    Article  CAS  Google Scholar 

  • 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 12:459–465

    Article  CAS  Google Scholar 

  • 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 82:583–590

    Article  CAS  Google Scholar 

  • Nilius B, Droogmans G (2001) Ion channels and their functional role in vascular endothelium. Physiol Rev 81:1415–1459

    CAS  Google Scholar 

  • 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 61:519–529

    Article  Google Scholar 

  • 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 5:701–705

    Article  Google Scholar 

  • 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 143:767–775

    Article  CAS  Google Scholar 

  • 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 25:2044–2052

    Article  CAS  Google Scholar 

  • 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 2:394–399

    Article  CAS  Google Scholar 

  • Peters NS (2005) Arrhythmias after cell transplantation for myocardial regeneration: natural history or result of the intervention? J Cardiovasc Electrophysiol 16:1255–1257

    Article  Google Scholar 

  • 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 251:131–136

    Article  CAS  Google Scholar 

  • Rao MS, Mattson MP (2001) Stem cells and aging: expanding the possibilities. Mech Ageing Dev 31:713–734

    Article  Google Scholar 

  • 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 164:247–256

    Article  CAS  Google Scholar 

  • 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 10:5

    Article  Google Scholar 

  • 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 30:1022–1026

    Google Scholar 

  • 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 73:1919–1925

    Article  Google Scholar 

  • 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 148:531–537

    Article  Google Scholar 

  • 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 52:1858–1865

    Article  CAS  Google Scholar 

  • 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 35:221–226

    Article  CAS  Google Scholar 

  • 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. 26:53–61

    Article  Google Scholar 

  • Von Zglinicki T, Martin-Ruiz CM (2005) Telomeres as biomarkers for ageing and age-related diseases. Curr Mol Med 5:197–203

    Article  Google Scholar 

  • 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 22:1330–1337

    Article  Google Scholar 

  • Weil BR, Canty JM Jr (2013) Stem cell stimulation of endogenous myocyte regeneration. Clin Sci (Lond) 125:109–119

    Article  CAS  Google Scholar 

  • 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 24:781–792

    Article  CAS  Google Scholar 

  • Zhang YM, Hartzell C, Narlow M, Dudley SC Jr (2002) Stem cell-derived cardiomyocytes demonstrate arrhythmic potential. Circulation 3:1294–1299

    Article  Google Scholar 

  • Zimmer T, Haufe V, Blechschmidt S (2014) Voltage-gated sodium channels in the mammalian heart. Glob Cardiol Sci Pract 31:449–463

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Nichi-Asia Life Sdn Bhd., 47810, Petaling Jaya, Selangor, Malaysia

    Baskar Subramani, Sellamuthu Subbannagounder & Chithra Ramanathanpullai

  2. Bharathiyar University, Coimbatore, Tamil Nadu, India

    Baskar Subramani

  3. Departments of Zoology, Government Arts College (Autonomous), Salem, 636007, Tamil Nadu, India

    Sekar Palanivel

  4. Cardiothoracic Surgery Unit, National Heart Institute, 50400, Kuala Lumpur, Malaysia

    Sivakumar Sivalingam & Azhari Yakub

  5. Micro Therapeutic Research Labs Pvt. Ltd, Chennai, Tamil Nadu, India

    Manjunath SadanandaRao

  6. Department of Veterinary Pathology and Microbiology, Universiti Putra Malaysia, Serdang, Malaysia

    Arivudainambi Seenichamy

  7. Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia

    Ashok Kumar Pandurangan

  8. Regeneration Medicine Cluster, Advanced Medicine and Dental Institute, Universiti Sains Malaysia, George Town, Pulau Pinang, Malaysia

    Jun Jie Tan

  9. Stem Cell and Immunity Group, Immunology Laboratory Unit, Department Of Pathology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia

    Rajesh Ramasamy

  10. Stem Cell Research Laboratory, Genetic and Regenerative Medicine Research Center, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia

    Rajesh Ramasamy

Authors
  1. Baskar Subramani
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sellamuthu Subbannagounder
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sekar Palanivel
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chithra Ramanathanpullai
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sivakumar Sivalingam
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Azhari Yakub
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Manjunath SadanandaRao
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Arivudainambi Seenichamy
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ashok Kumar Pandurangan
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Jun Jie Tan
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Rajesh Ramasamy
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rajesh Ramasamy.

Ethics declarations

Conflict of interest

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Subramani, B., Subbannagounder, S., Palanivel, S. et al. Generation and characterization of human cardiac resident and non-resident mesenchymal stem cell. Cytotechnology 68, 2061–2073 (2016). https://doi.org/10.1007/s10616-016-9946-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10616-016-9946-5

Keywords

Search

Navigation