Cellular and Molecular Life Sciences

, Volume 76, Issue 9, pp 1681–1695 | Cite as

Therapeutic potential of menstrual blood-derived endometrial stem cells in cardiac diseases

  • Yanli Liu
  • Rongcheng Niu
  • Wenzhong LiEmail author
  • Juntang LinEmail author
  • Christof Stamm
  • Gustav Steinhoff
  • Nan Ma


Despite significant developments in medical and surgical strategies, cardiac diseases remain the leading causes of morbidity and mortality worldwide. Numerous studies involving preclinical and clinical trials have confirmed that stem cell transplantation can help improve cardiac function and regenerate damaged cardiac tissue, and stem cells isolated from bone marrow, heart tissue, adipose tissue and umbilical cord are the primary candidates for transplantation. During the past decade, menstrual blood-derived endometrial stem cells (MenSCs) have gradually become a promising alternative for stem cell-based therapy due to their comprehensive advantages, which include their ability to be periodically and non-invasively collected, their abundant source material, their ability to be regularly donated, their superior proliferative capacity and their ability to be used for autologous transplantation. MenSCs have shown positive therapeutic potential for the treatment of various diseases. Therefore, aside from a brief introduction of the biological characteristics of MenSCs, this review focuses on the progress being made in evaluating the functional improvement of damaged cardiac tissue after MenSC transplantation through preclinical and clinical studies. Based on published reports, we conclude that the paracrine effect, transdifferentiation and immunomodulation by MenSC promote both regeneration of damaged myocardium and improvement of cardiac function.


Cardiac regeneration Stem cell-based therapy Menstrual blood-derived endometrial stem cells Cardiac disease 



We would like to acknowledge the China Scholarship Council, the National Natural Science Foundation of China (81671619 and 81771226) and the Xinxiang Foundation (20172DCG-03 and ZD17008) for their financial support.

Compliance with ethical standards

Conflict of interest

The authors declare that there are no conflicts of interest regarding the publication of this paper.


  1. 1.
    Young PP, Schäfer R (2015) Cell-based therapies for cardiac disease: a cellular therapist’s perspective. Transfusion 55(2):441–451CrossRefPubMedGoogle Scholar
  2. 2.
    Lloyd-Jones D, Adams R, Carnethon M et al (2009) Heart disease and stroke statistics-2009 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 119(3):480–486CrossRefPubMedGoogle Scholar
  3. 3.
    Laflamme MA, Murry CE (2011) Heart regeneration. Nature 473(7347):326CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Miranović V (2016) The incidence of congenital heart defects in the world regarding the severity of the defect. Vojnosanit Pregl 73(2):159–164CrossRefPubMedGoogle Scholar
  5. 5.
    Breckwoldt K, Weinberger F, Eschenhagen T (2016) Heart regeneration. BBA-Mol. Cell Res 1863(7):1749–1759Google Scholar
  6. 6.
    Bergmann O, Zdunek S, Felker A et al (2015) Dynamics of cell generation and turnover in the human heart. Cell 161(7):1566–1575CrossRefPubMedGoogle Scholar
  7. 7.
    Tongers J, Losordo DW, Landmesser U (2011) Stem and progenitor cell-based therapy in ischaemic heart disease: promise, uncertainties, and challenges. Eur Heart J 32(10):1197–1206CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Dixit P, Katare R (2015) Challenges in identifying the best source of stem cells for cardiac regeneration therapy. Stem Cell Res Ther 6(1):26CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Bolli R, Ghafghazi S (2017) Stem cells: cell therapy for cardiac repair: what is needed to move forward? Nat Rev Cardiol 14(5):257CrossRefPubMedGoogle Scholar
  10. 10.
    Meng X, Ichim TE, Zhong J et al (2007) Endometrial regenerative cells: a novel stem cell population. J Transl Med 5(1):57CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Xu Y, Zhu H, Zhao D et al (2015) Endometrial stem cells: clinical application and pathological roles. Int J Clin Exp Med 8(12):22039PubMedPubMedCentralGoogle Scholar
  12. 12.
    Gargett CE, Schwab KE, Deane JA (2015) Endometrial stem/progenitor cells: the first 10 years. Hum Reprod Update 22(2):137–163PubMedPubMedCentralGoogle Scholar
  13. 13.
    Simoni M, Taylor HS (2018) Therapeutic strategies involving uterine stem cells in reproductive medicine. Curr Opin Obstet Gyn 30(3):209–216Google Scholar
  14. 14.
    Lemcke H, Voronina N, Steinhoff G et al (2018) Recent progress in stem cell modification for cardiac regeneration. Stem Cells Int. CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Minguell JJ, Erices A (2006) Mesenchymal stem cells and the treatment of cardiac disease. Expl Biol Med 231(1):39–49CrossRefGoogle Scholar
  16. 16.
    Iglesias-García O, Pelacho B, Prósper F (2013) Induced pluripotent stem cells as a new strategy for cardiac regeneration and disease modeling. J Mol Cell Cardiol 62:43–50CrossRefPubMedGoogle Scholar
  17. 17.
    Rikhtegar R, Pezeshkian M, Dolati S et al (2019) Stem cells as therapy for heart disease: iPSCs, ESCs, CSCs, and skeletal myoblasts. Biomed Pharmacother 109:304–313CrossRefPubMedGoogle Scholar
  18. 18.
    Berardi GRM, Rebelatto CK, Tavares HF et al (2011) Transplantation of SNAP-treated adipose tissue-derived stem cells improves cardiac function and induces neovascularization after myocardium infarct in rats. Exp Mol Pathol 90(2):149–156CrossRefPubMedGoogle Scholar
  19. 19.
    Ou L, Li W, Liu Y et al (2010) Animal models of cardiac disease and stem cell therapy. Open Cardiovasc Med J 4:231–239CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Li W, Ma N, Ong LL et al (2007) Bcl-2 engineered MSCs inhibited apoptosis and improved heart function. Stem Cells 25:2118–2127CrossRefPubMedGoogle Scholar
  21. 21.
    Menasché P, Vanneaux V, Hagège A et al (2015) Human embryonic stem cell-derived cardiac progenitors for severe heart failure treatment: first clinical case report. Eur Heart J 36:2011–2017CrossRefPubMedGoogle Scholar
  22. 22.
    Menasché P, Vanneaux V, Hagège A et al (2018) Transplantation of human embryonic stem cell-derived cardiovascular progenitors for severe ischemic left ventricular dysfunction. J Am Coll Cardiol 71:429–438CrossRefPubMedGoogle Scholar
  23. 23.
    Narita T, Suzuki K (2015) Bone marrow-derived mesenchymal stem cells for the treatment of heart failure. Heart Fail Rev 20(1):53–68CrossRefPubMedGoogle Scholar
  24. 24.
    Wollert KC, Meyer GP, Lotz J et al (2004) Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial. Lancet 364(9429):141–148CrossRefPubMedGoogle Scholar
  25. 25.
    Broughton KM, Sussman MA (2018) Enhancement strategies for cardiac regenerative cell therapy: focus on adult stem cells. Circ Res 123(2):177–187CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Nascimento DS, MosqueiraD Sousa LM et al (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 5(1):5CrossRefPubMedCentralGoogle Scholar
  27. 27.
    Banerjee MN, Bolli R, Hare JM (2018) Clinical studies of cell therapy in cardiovascular medicine: recent developments and future directions. Circ Res 123(2):266–287CrossRefPubMedGoogle Scholar
  28. 28.
    Gaebel R, Furlani D, Sorg H et al (2011) Cell origin of human mesenchymal stem cells determines a different healing performance in cardiac regeneration. PLoS One 6:e15652CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Ma N, Ladilov Y, Moebius JM et al (2006) Intramyocardial delivery of human CD133 + cells in a SCID mouse cryoinjury model: bone marrow vs. cord blood-derived cells. Cardiovasc Res 71:158–169CrossRefPubMedGoogle Scholar
  30. 30.
    Nakamura Y, Suzuki S, Shimizu T et al (2015) High mobility group box 1 promotes angiogenesis from bone marrow-derived endothelial progenitor cells after myocardial infarction. J Atheroscler Thromb 22(6):570–581CrossRefPubMedGoogle Scholar
  31. 31.
    Bianco P, Riminucci M, Gronthos S et al (2001) Bone marrow stromal stem cells: nature, biology, and potential applications. Stem Cells 19(3):180–192CrossRefPubMedGoogle Scholar
  32. 32.
    Yu VWC, Scadden DT (2016) Heterogeneity of the bone marrow niche. Curr Opin Hematol 23(4):331–338CrossRefPubMedGoogle Scholar
  33. 33.
    Asahara T, Murohara T, Sullivan A et al (1997) Isolation of putative progenitor endothelial cells for angiogenesis. Science 275(5302):964–966CrossRefPubMedGoogle Scholar
  34. 34.
    Nesselmann C, Li W, Ma N et al (2010) Stem cell-mediated neovascularization in heart repair. Ther Adv Cardiovasc Dis 4(1):27–42CrossRefPubMedGoogle Scholar
  35. 35.
    Orlic D, Kajstura J, Chimenti S et al (2001) Bone marrow cells regenerate infarcted myocardium. Nature 410(6829):701–705CrossRefPubMedGoogle Scholar
  36. 36.
    Miyahara Y, Nagaya N, Kataoka M et al (2006) Monolayered mesenchymal stem cells repair scarred myocardium after myocardial infarction. Nat Med 12(4):459–465CrossRefPubMedGoogle Scholar
  37. 37.
    Amado LC, Saliaris AP, Schuleri KH et al (2005) Cardiac repair with intramyocardial injection of allogeneic mesenchymal stem cells after myocardial infarction. PNAS 102(32):11474–11479CrossRefPubMedGoogle Scholar
  38. 38.
    Ryan JM, Barry FP, Murphy JM et al (2005) Mesenchymal stem cells avoid allogeneic rejection. J Inflamm 2(1):8CrossRefGoogle Scholar
  39. 39.
    Strauer BE, Brehm M, Zeus T et al (2005) Regeneration of human infarcted heart muscle by intracoronary autologous bone marrow cell transplantation in chronic coronary artery disease: the IACT Study. J Am Coll Cardiol 46(9):1651–1658CrossRefPubMedGoogle Scholar
  40. 40.
    Breitbach M, Bostani T, Roell W et al (2007) Potential risks of bone marrow cell transplantation into infarcted hearts. Blood 110(4):1362–1369CrossRefPubMedGoogle Scholar
  41. 41.
    Mao C, Hou X, Wang B et al (2017) Intramuscular injection of human umbilical cord-derived mesenchymal stem cells improves cardiac function in dilated cardiomyopathy rats. Stem Cell Res Ther 8(1):18CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Bartolucci JG, Verdugo FJ, González PL et al (2017) Safety and efficacy of the intravenous infusion of umbilical cord mesenchymal stem cells in patients with heart failure: a phase 1/2 randomized controlled trial (RIMECARD Trial). Circ Res. CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Mazo M, Gavira JJ, Pelacho B et al (2011) Adipose-derived stem cells for myocardial infarction. J Cardiovasc Transl 4(2):145–153CrossRefGoogle Scholar
  44. 44.
    Kastrup J, Haack-Sørensen M, Juhl M et al (2017) Cryopreserved off-the-shelf allogeneic adipose-derived stromal cells for therapy in patients with ischemic heart disease and heart failure-A Safety Study. Stem Cell Transl Med 6(11):1963–1971CrossRefGoogle Scholar
  45. 45.
    Matsuura K, Nagai T, Nishigaki N et al (2004) Adult cardiac Sca-1-positive cells differentiate into beating cardiomyocytes. J Biol Chem 279(12):11384–11391CrossRefPubMedGoogle Scholar
  46. 46.
    Laugwitz KL, Moretti A, Lam J et al (2005) Postnatal isl1 + cardioblasts enter fully differentiated cardiomyocyte lineages. Nature 433(7026):647–652CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Yellamilli A, van Berlo JH (2016) The role of cardiac side population cells in cardiac regeneration. Front Cell Dev Biol 4:102CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Zhou B, Ma Q, Rajagopal S et al (2008) Epicardial progenitors contribute to the cardiomyocyte lineage in the developing heart. Nature 454(7200):109CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Chong JJH, Chandrakanthan V, Xaymardan M et al (2011) Adult cardiac-resident MSC-like stem cells with a proepicardial origin. Cell Stem Cell 9(6):527–540CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Santini MP, Forte E, Harvey RP et al (2016) Developmental origin and lineage plasticity of endogenous cardiac stem cells. Development 143(8):1242–1258CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    van Berlo JH, Kanisicak O, Maillet M et al (2014) c-kit + Cells minimally contribute cardiomyocytes to the heart. Nature 509:337–341CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Sultana N, Zhang L, Yan J et al (2015) Resident c-kit + cells in the heart are not cardiac stem cells. Nat Commun 6:8701CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Maliken BD, Molkentin JD (2018) Undeniable evidence that the adult mammalian heart lacks an endogenous regenerative stem cell. Circulation 138(8):806–808CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Minteer D, Marra KG, Rubin JP (2013) Adipose derived mesenchymal stem cells: biology and potential applications. Adv Biochem Eng Biotechnol 129:59–71PubMedGoogle Scholar
  55. 55.
    Dalous J, Larghero J, Baud O (2012) Transplantation of umbilical cord-derived mesenchymal stem cells as a novel strategy to protect the central nervous system: technical aspects, preclinical studies, and clinical perspectives. Pediatr Res 71:482–490CrossRefPubMedGoogle Scholar
  56. 56.
    Tolar J, Nauta AJ, Osborn MJ et al (2007) Sarcoma derived from cultured mesenchymal stem cells. Stem Cells 25:371–379CrossRefPubMedGoogle Scholar
  57. 57.
    Jeong JO, Han JW, Kim JM et al (2011) Malignant tumor formation after transplantation of short-term cultured bone marrow mesenchymal stem cells in experimental myocardial infarction and diabetic neuropathy. Circ Res 108:1340–1347CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Kamat P, Schweizer R, Kaenel P et al (2015) Human adipose-derived mesenchymal stromal cells may promote breast cancer progression and metastatic spread. Plast Reconstr Surg 136:76–84CrossRefPubMedGoogle Scholar
  59. 59.
    Karnoub AE, Dash AB, Vo AP et al (2007) Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature 449:557–563CrossRefPubMedGoogle Scholar
  60. 60.
    Cui CH, Uyama T, Miyado K et al (2007) Menstrual blood-derived cells confer human dystrophin expression in the murine model of Duchenne muscular dystrophy via cell fusion and myogenic transdifferentiation. Mol Biol Cell 18(5):1586–1594CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Hida N, Nishiyama N, Miyoshi S et al (2008) Novel cardiac precursor-like cells from human menstrual blood-derived mesenchymal cells. Stem cells 26(7):1695–1704CrossRefPubMedGoogle Scholar
  62. 62.
    Han X, Meng X, Yin Z et al (2009) Inhibition of intracranial glioma growth by endometrial regenerative cells. Cell Cycle 8(4):606–610CrossRefPubMedGoogle Scholar
  63. 63.
    Borlongan CV, Kaneko Y, Maki M et al (2010) Menstrual blood cells display stem cell-like phenotypic markers and exert neuroprotection following transplantation in experimental stroke. Stem Cells Dev 19(4):439–452CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Peron JPS, Jazedje T, Brandao WN et al (2012) Human endometrial-derived mesenchymal stem cells suppress inflammation in the central nervous system of EAE mice. Stem Cell Rev Rep 8(3):940–952CrossRefPubMedGoogle Scholar
  65. 65.
    Mou X, Lin J, Chen J et al (2013) Menstrual blood-derived mesenchymal stem cells differentiate into functional hepatocyte-like cells. J Zhejiang Univ Sci B 14(11):961–972CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Zhang Z, Wang J, Xu Y et al (2013) Menstrual blood derived mesenchymal cells ameliorate cardiac fibrosis via inhibition of endothelial to mesenchymal transition in myocardial infarction. Int J Cardiol 168(2):1711–1714CrossRefPubMedGoogle Scholar
  67. 67.
    Liu T, Huang Y, Zhang J et al (2014) Transplantation of human menstrual blood stem cells to treat premature ovarian failure in mouse model. Stem Cells Dev 23(13):1548–1557CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Wu X, Luo Y, Chen J et al (2014) Transplantation of human menstrual blood progenitor cells improves hyperglycemia by promoting endogenous progenitor differentiation in type 1 diabetic mice. Stem Cells Dev 23(11):1245–1257CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Lv Y, Xu X, Zhang B et al (2014) Endometrial regenerative cells as a novel cell therapy attenuate experimental colitis in mice. J Transl Med 12(1):344CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Alcayaga-Miranda F, Cuenca J, Martin A et al (2015) Combination therapy of menstrual derived mesenchymal stem cells and antibiotics ameliorates survival in sepsis. Stem Cell Res Ther 6(1):1–13CrossRefGoogle Scholar
  71. 71.
    Sun P, Liu J, Li W et al (2016) Human endometrial regenerative cells attenuate renal ischemia reperfusion injury in mice. J Transl Med 14(1):1–13CrossRefGoogle Scholar
  72. 72.
    Lu S, Shi G, Xu X et al (2016) Human endometrial regenerative cells alleviate carbon tetrachloride-induced acute liver injury in mice. J Transl Med 14(1):300CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Chen L, Zhang C, Chen L et al (2017) Human menstrual blood-derived stem cells ameliorate liver fibrosis in mice by targeting hepatic stellate cells via paracrine mediators. Stem Cells Transl Med 6(1):272–284CrossRefPubMedGoogle Scholar
  74. 74.
    Zhang Y, Lin X, Dai Y et al (2016) Endometrial stem cells repair injured endometrium and induce angiogenesis via AKT and ERK pathways. Reproduction 152(5):389–402CrossRefPubMedGoogle Scholar
  75. 75.
    Xu X, Li X, Gu X et al (2017) Prolongation of cardiac allograft survival by endometrial regenerative cells: focusing on b-cell responses. Stem Cells Transl Med 6(3):778–787CrossRefPubMedGoogle Scholar
  76. 76.
    Lan X, Wang G, Xu X et al (2017) Stromal cell-derived factor-1 mediates cardiac allograft tolerance induced by human endometrial regenerative cell-based therapy. Stem Cells Transl Med 6(11):1997–2008CrossRefPubMedPubMedCentralGoogle Scholar
  77. 77.
    Xiang B, Chen L, Wang X et al (2017) Transplantation of menstrual blood-derived mesenchymal stem cells promotes the repair of LPS-induced acute lung injury. Int J Mol Sci 18(4):689CrossRefPubMedCentralGoogle Scholar
  78. 78.
    Fathi-Kazerooni M, Tavoosidana G, Taghizadeh-Jahed M et al (2017) Comparative restoration of acute liver failure by menstrual blood stem cells compared with bone marrow stem cells in mice model. Cytotherapy 19(12):1474–1490CrossRefPubMedGoogle Scholar
  79. 79.
    Domnina A, Novikova P, Obidina J et al (2018) Human mesenchymal stem cells in spheroids improve fertility in model animals with damaged endometrium. Stem Cell Res Ther 9(1):50CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Zhao Y, Chen X, Wu Y et al (2018) Transplantation of human menstrual blood-derived mesenchymal stem cells alleviates Alzheimer’s disease-like pathology in APP/PS1 transgenic mice. Front Mol Neurosci 11:140CrossRefPubMedPubMedCentralGoogle Scholar
  81. 81.
    Tan J, Li P, Wang Q et al (2016) Autologous menstrual blood-derived stromal cells transplantation for severe Asherman’s syndrome. Hum Reprod 31(12):2723–2729CrossRefPubMedGoogle Scholar
  82. 82.
    Ichim TE, Alexandrescu DT, Solano F et al (2010) Mesenchymal stem cells as anti-inflammatories: implications for treatment of Duchenne muscular dystrophy. Cell Immunol 260(2):75–82CrossRefPubMedGoogle Scholar
  83. 83.
    Ichim TE, Solano F, Lara F et al (2010) Combination stem cell therapy for heart failure. Int Arch Med 3(1):5CrossRefPubMedPubMedCentralGoogle Scholar
  84. 84.
    Bockeria L, Bogin V, Bockeria O et al (2013) Endometrial regenerative cells for treatment of heart failure: a new stem cell enters the clinic. J Transl Med 11(5):56CrossRefPubMedPubMedCentralGoogle Scholar
  85. 85.
    Mclennan CE, Rydell ALFH (1965) Extent of endometrial shedding during normal menstruation. Obst Gyn 26(5):605–621Google Scholar
  86. 86.
    Gargett CE (2007) Uterine stem cells: what is the evidence? Hum Reprod Update 13(1):87–101CrossRefPubMedGoogle Scholar
  87. 87.
    Gargett CE, Masuda H (2010) Adult stem cells in the endometrium. Mol Hum Reprod 16(11):818–834CrossRefPubMedGoogle Scholar
  88. 88.
    Liu Y, Niu R, Yang F et al (2018) Biological characteristics of human menstrual blood-derived endometrial stem cells. J Cell Mol Med 22(3):1627–1639CrossRefPubMedGoogle Scholar
  89. 89.
    Bolli R (2017) Repeated cell therapy: a paradigm shift whose time has come. Circ Res 120(7):1072–1074CrossRefPubMedPubMedCentralGoogle Scholar
  90. 90.
    Wang Y, Han ZB, Ma J et al (2011) A toxicity study of multiple-administration human umbilical cord mesenchymal stem cells in cynomolgus monkeys. Stem Cells Dev 21(9):1401–1408CrossRefPubMedGoogle Scholar
  91. 91.
    Tokita Y, Tang XL, Li Q et al (2016) Repeated administrations of cardiac progenitor cells are markedly more effective than a single administration: a new paradigm in cell therapy. Circ Res 119(5):635–651CrossRefPubMedPubMedCentralGoogle Scholar
  92. 92.
    Mann I, Rodrigo SF, van Ramshorst J et al (2015) Repeated intramyocardial bone marrow cell injection in previously responding patients with refractory angina again improves myocardial perfusion, anginal complaints, and quality of life. Circ Cardiovasc Int 8(8):e002740Google Scholar
  93. 93.
    Tang XL, Nakamura S, Li Q et al (2018) Repeated administrations of cardiac progenitor cells are superior to a single administration of an equivalent cumulative dose. J Am Heart Assoc 7(4):e007400CrossRefPubMedPubMedCentralGoogle Scholar
  94. 94.
    Masuda H, Anwar SS, Bühring HJ et al (2012) A novel marker of human endometrial mesenchymal stem-like cells. Cell Transpl 21(10):2201–2214CrossRefGoogle Scholar
  95. 95.
    Schwab KE, Gargett CE (2007) Co-expression of two perivascular cell markers isolates mesenchymal stem-like cells from human endometrium. Hum Reprod 22(11):2903–2911CrossRefPubMedGoogle Scholar
  96. 96.
    Cervelló I, Gil-Sanchis C, Mas A et al (2010) Human endometrial side population cells exhibit genotypic, phenotypic and functional features of somatic stem cells. PLoS One 5(6):e10964CrossRefPubMedPubMedCentralGoogle Scholar
  97. 97.
    Masuda H, Matsuzaki Y, Hiratsu E et al (2010) Stem cell-like properties of the endometrial side population: implication in endometrial regeneration. PLoS One 5(4):e10387CrossRefPubMedPubMedCentralGoogle Scholar
  98. 98.
    Kamp TJ (2011) Recognizing heart cells in a crowd. Nat Methods 8(12):1013CrossRefPubMedGoogle Scholar
  99. 99.
    Li TS, Cheng K, Malliaras K et al (2012) Direct comparison of different stem cell types and subpopulations reveals superior paracrine potency and myocardial repair efficacy with cardiosphere-derived cells. J Am Coll Cardiol 59(10):942–953CrossRefPubMedPubMedCentralGoogle Scholar
  100. 100.
    Patel AN, Park E, Kuzman M et al (2008) Multipotent menstrual blood stromal stem cells: isolation, characterization, and differentiation. Cell Transpl 17(3):303–311CrossRefGoogle Scholar
  101. 101.
    Calloni R, Cordero EAA, Henriques JAP et al (2013) Reviewing and updating the major molecular markers for stem cells. Stem Cells Dev 22(9):1455–1476CrossRefPubMedPubMedCentralGoogle Scholar
  102. 102.
    Sani F, Borzooeian G, Kazemnejad S et al (2016) Differentiation of menstrual blood derived stem cell (MensSCs) to hepatocyte-liked cell on three dimensional nanofiberscaffold: poly caprolacton (PCL). J Biomed Sci Eng 9(04):216CrossRefGoogle Scholar
  103. 103.
    Faramarzi H, Mehrabani D, Fard M et al (2016) The potential of menstrual blood-derived stem cells in differentiation to epidermal lineage: a preliminary report. World J Plast Surg 5(1):26PubMedPubMedCentralGoogle Scholar
  104. 104.
    Chen X, Kong X, Liu D et al (2016) In vitro differentiation of endometrial regenerative cells into smooth muscle cells: a potential approach for the management of pelvic organ prolapse. Int J Mol Med 38(1):95–104CrossRefPubMedPubMedCentralGoogle Scholar
  105. 105.
    Zheng SX, Wang J, Wang XL et al (2018) Feasibility analysis of treating severe intrauterine adhesions by transplanting menstrual blood-derived stem cells. Int J Mol Med 41(4):2201–2212PubMedGoogle Scholar
  106. 106.
    Lai D, Guo Y, Zhang Q et al (2016) Differentiation of human menstrual blood-derived endometrial mesenchymal stem cells into oocyte-like cells. Acta Bioch Bioph Sin 48(11):998–1005CrossRefGoogle Scholar
  107. 107.
    Akhavan-Tavakoli M, Fard M, Khanjani S et al (2017) In vitro differentiation of menstrual blood stem cells into keratinocytes: a potential approach for management of wound healing. Biologicals 48:66–73CrossRefPubMedGoogle Scholar
  108. 108.
    Jiang Z, Hu X, Yu H et al (2013) Human endometrial stem cells confer enhanced myocardial salvage and regeneration by paracrine mechanisms. J Cell Mol Med 17(10):1247–1260CrossRefPubMedPubMedCentralGoogle Scholar
  109. 109.
    Szaraz P, Gratch YS, Iqbal F et al (2017) In vitro differentiation of human mesenchymal stem cells into functional cardiomyocyte-like cells. J Vis Exp 126:e55757Google Scholar
  110. 110.
    Pei Z, Zeng J, Song Y et al (2017) In vivo imaging to monitor differentiation and therapeutic effects of transplanted mesenchymal stem cells in myocardial infarction. Sci Rep 7(1):6296CrossRefPubMedPubMedCentralGoogle Scholar
  111. 111.
    Balsam LB, Wagers AJ, Christensen JL et al (2004) Haematopoietic stem cells adopt mature haematopoietic fates in ischaemic myocardium. Nature 428(6983):668CrossRefPubMedGoogle Scholar
  112. 112.
    Bagno L, Hatzistergos KE, Balkan W et al (2018) Mesenchymal stem cell-based therapy for cardiovascular disease: progress and challenges. Mol Ther 26(7):1610–1623CrossRefPubMedPubMedCentralGoogle Scholar
  113. 113.
    Kardami E, Banerji S, Doble BW et al (2003) PKC-dependent phosphorylation may regulate the ability of connexin43 to inhibit DNA synthesis. Cell Commun Adhes 10:293–297CrossRefPubMedGoogle Scholar
  114. 114.
    Hinrichsen R, Haunso S, Busk PK (2007) Different regulation of p27 and Akt during cardiomyocyte proliferation and hypertrophy. Growth Fact 25:132–140CrossRefGoogle Scholar
  115. 115.
    Zhou B, Honor LB, He H et al (2011) Adult mouse epicardium modulates myocardial injury by secreting paracrine factors. J Clin Invest 121:1894–1904CrossRefPubMedPubMedCentralGoogle Scholar
  116. 116.
    Przybyt E, Krenning G, Brinker MG et al (2013) Adipose stromal cells primed with hypoxia and inflammation enhance cardiomyocyte proliferation rate in vitro through STAT3 and Erk1/2. J Transl Med 11:39CrossRefPubMedPubMedCentralGoogle Scholar
  117. 117.
    Novoyatleva T, Diehl F, van Amerongen MJ et al (2010) TWEAK is a positive regulator of cardiomyocyte proliferation. Cardiovasc Res 85:681–690CrossRefPubMedGoogle Scholar
  118. 118.
    Lemmens K, Doggen K, De Keulenaer GW (2007) Role of neuregulin-1/ErbB signaling in cardiovascular physiology and disease: implications for therapy of heart failure. Circulation 116:954–960CrossRefPubMedPubMedCentralGoogle Scholar
  119. 119.
    Kuhn B, del Monte F, Hajjar RJ et al (2007) Periostin induces proliferation of differentiated cardiomyocytes and promotes cardiac repair. Nat Med 13:962–969CrossRefPubMedGoogle Scholar
  120. 120.
    Nygren JM, Jovinge S, Breitbach M et al (2004) Bone marrow-derived hematopoietic cells generate cardiomyocytes at a low frequency through cell fusion, but not transdifferentiation. Nat Med 10(5):494CrossRefPubMedGoogle Scholar
  121. 121.
    Malliaras K, Marbán E (2011) Cardiac cell therapy: where we’ve been, where we are, and where we should be headed. Brit Med Bull 98(1):161–185CrossRefPubMedGoogle Scholar
  122. 122.
    Golpanian S, Wolf A, Hatzistergos KE et al (2016) Rebuilding the damaged heart: mesenchymal stem cells, cell-based therapy, and engineered heart tissue. Physiol Rev 96(3):1127–1168CrossRefPubMedPubMedCentralGoogle Scholar
  123. 123.
    Beigi F, Schmeckpeper J, Pow-anpongkul P et al (2013) C3orf58, a novel paracrine protein, stimulates cardiomyocyte cell-cycle progression through the PI3K–AKT–CDK7 pathway. Circ Res 113(4):372–380CrossRefPubMedGoogle Scholar
  124. 124.
    Chen L, Xiang B, Wang X et al (2017) Exosomes derived from human menstrual blood-derived stem cells alleviate fulminant hepatic failure. Stem Cell Res Ther 8(1):9CrossRefPubMedPubMedCentralGoogle Scholar
  125. 125.
    Hu X, Yu SP, Fraser JL et al (2008) Transplantation of hypoxia-preconditioned mesenchymal stem cells improves infarcted heart function via enhanced survival of implanted cells and angiogenesis. J Thorac Cardiovasc Surg 135(4):799–808CrossRefPubMedGoogle Scholar
  126. 126.
    Yan F, Yao Y, Chen L et al (2012) Hypoxic preconditioning improves survival of cardiac progenitor cells: role of stromal cell derived factor-1α–CXCR4 axis. PLoS One 7(7):e37948CrossRefPubMedPubMedCentralGoogle Scholar
  127. 127.
    Butler J, Epstein SE, Greene SJ et al (2017) Intravenous allogeneic mesenchymal stem cells for nonischemic cardiomyopathy: safety and efficacy results of a phase II—a randomized trial. Circ Res 120(2):332–340CrossRefPubMedGoogle Scholar
  128. 128.
    Makrigiannakis A, Karamouti M, Drakakis P et al (2008) Fetomaternal immunotolerance. Am J Reprod Immunol 60(6):482–496CrossRefPubMedGoogle Scholar
  129. 129.
    Nikoo S, Ebtekar M, Jeddi-Tehrani M et al (2012) Effect of menstrual blood-derived stromal stem cells on proliferative capacity of peripheral blood mononuclear cells in allogeneic mixed lymphocyte reaction. J Obstet Gynaecol Res 38(5):804–809CrossRefPubMedGoogle Scholar
  130. 130.
    Murphy MP, Wang H, Patel AN et al (2008) Allogeneic endometrial regenerative cells: an “Off the shelf solution” for critical limb ischemia? J Transl Med 6(1):45CrossRefPubMedPubMedCentralGoogle Scholar
  131. 131.
    Weidner CI, Walenda T, Lin Q et al (2013) Hematopoietic stem and progenitor cells acquire distinct DNA-hypermethylation during in vitro culture. Sci Rep 3:3372CrossRefPubMedPubMedCentralGoogle Scholar
  132. 132.
    Le Blanc K, Frassoni F, Ball L et al (2008) Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet 371(9624):1579–1586CrossRefPubMedGoogle Scholar
  133. 133.
    Campisi J, di Fagagna FA (2007) Cellular senescence: when bad things happen to good cells. Nat Rev Mol Cell Biol 8(9):729CrossRefPubMedGoogle Scholar
  134. 134.
    Quyyumi AA, Waller EK, Murrow J et al (2011) CD34 + cell infusion after ST elevation myocardial infarction is associated with improved perfusion and is dose dependent. Am Heart J 161(1):98–105CrossRefPubMedGoogle Scholar
  135. 135.
    Florea V, Rieger AC, DiFede DL et al (2017) Dose comparison study of allogeneic mesenchymal stem cells in patients with ischemic cardiomyopathy (The TRIDENT Study). Circ Res 121(11):1279–1290CrossRefPubMedGoogle Scholar
  136. 136.
    Perin EC, Borow KM, Silva GV et al (2015) A phase II dose-escalation study of allogeneic mesenchymal precursor cells in patients with ischemic or nonischemic heart failure. Circ Res 117(6):576–584CrossRefPubMedGoogle Scholar
  137. 137.
    Losordo DW, Henry TD, Davidson C et al (2011) Intramyocardial, autologous CD34 + cell therapy for refractory angina. Circ Res 109(4):428–436CrossRefPubMedPubMedCentralGoogle Scholar
  138. 138.
    Hare JM, Fishman JE, Gerstenblith G et al (2012) Comparison of allogeneic vs autologous bone marrow–derived mesenchymal stem cells delivered by transendocardial injection in patients with ischemic cardiomyopathy: the POSEIDON randomized trial. JAMA 308(22):2369–2379CrossRefPubMedPubMedCentralGoogle Scholar
  139. 139.
    Golpanian S, Schulman IH, Ebert RF et al (2016) Concise review: review and perspective of cell dosage and routes of administration from preclinical and clinical studies of stem cell therapy for heart disease. Stem Cell Transl Med 5(2):186–191CrossRefGoogle Scholar
  140. 140.
    Price MJ, Chou CC, Frantzen M et al (2006) Intravenous mesenchymal stem cell therapy early after reperfused acute myocardial infarction improves left ventricular function and alters electrophysiologic properties. Int J Cardiol 111(2):231–239CrossRefPubMedGoogle Scholar
  141. 141.
    Rigol M, Solanes N, Farré J et al (2010) Effects of adipose tissue-derived stem cell therapy after myocardial infarction: impact of the route of administration. J Card Fail 16(4):357–366CrossRefPubMedGoogle Scholar
  142. 142.
    Huang P, Tian X, Li Q et al (2016) New strategies for improving stem cell therapy in ischemic heart disease. Heart Fail Rev 21(6):737–752CrossRefPubMedGoogle Scholar
  143. 143.
    Vulliet PR, Greeley M, Halloran SM et al (2004) Intra-coronary arterial injection of mesenchymal stromal cells and microinfarction in dogs. Lancet 363(9411):783–784CrossRefPubMedGoogle Scholar
  144. 144.
    Perin EC, Silva GV, Hare JA et al (2008) Comparison of intracoronary and transendocardial delivery of allogeneic mesenchymal cells in a canine model of acute myocardial infarction. J Mol Cell Cardiol 44(3):486–495CrossRefPubMedGoogle Scholar
  145. 145.
    Vrtovec B, Poglajen G, Lezaic L et al (2013) Comparison of transendocardial and intracoronary CD34 + cell transplantation in patients with nonischemic dilated cardiomyopathy. Circulation 128(11 suppl 1):S42–S49CrossRefPubMedGoogle Scholar
  146. 146.
    Vrtovec B, Poglajen G, Lezaic L et al (2013) Effects of intracoronary CD34 + stem cell transplantation in nonischemic dilated cardiomyopathy patients: 5-year follow-up. Circ Res 112(1):165–173CrossRefPubMedGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Stem Cell and Biotherapy Technology Research Center, College of Life Science and Technology, Henan Key Laboratory of Medical Tissue RegenerationXinxiang Medical UniversityXinxiangPeople’s Republic of China
  2. 2.Institute of Chemistry and BiochemistryFree University BerlinBerlinGermany
  3. 3.Deutsches Herzzentrum Berlin (DHZB)BerlinGermany
  4. 4.German Center for Cardiovascular Research (DZHK)BerlinGermany
  5. 5.Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu BerlinBerlinGermany
  6. 6.Berlin Institute of HealthBerlinGermany
  7. 7.Department of Cardiac Surgery, Reference and Translation Center for Cardiac Stem Cell TherapyUniversity RostockRostockGermany
  8. 8.Institute of Biomaterial Science and Berlin-Brandenburg Center for Regenerative TherapiesHelmholtz-Zentrum GeesthachtTeltowGermany

Personalised recommendations