Skip to main content

Advertisement

SpringerLink
Log in

Placental mesenchymal stromal cells as an alternative tool for therapeutic angiogenesis

  • Review
  • Published:
Cellular and Molecular Life Sciences Aims and scope Submit manuscript

Abstract

Dysregulation of angiogenesis is a phenomenon observed in several disorders such as diabetic foot, critical limb ischemia and myocardial infarction. Mesenchymal stromal cells (MSCs) possess angiogenic potential and have recently emerged as a powerful tool for cell therapy to promote angiogenesis. Although bone marrow-derived MSCs are the primary cell of choice, obtaining them has become a challenge. The placenta has become a popular alternative as it is a highly vascular organ, easily available and ethically more favorable with a rich supply of MSCs. Comparatively, placenta-derived MSCs (PMSCs) are clinically promising due to their proliferative, migratory, clonogenic and immunomodulatory properties. PMSCs release a plethora of cytokines and chemokines key to angiogenic signaling and facilitate the possibility of delivering PMSC-derived exosomes as a targeted therapy to promote angiogenesis. However, there still remains the challenge of heterogeneity in the isolated populations, questions on the maternal or fetal origin of these cells and the diversity in previously reported isolation and culture conditions. Nonetheless, the growing rate of clinical trials using PMSCs clearly indicates a shift in favor of PMSCs. The overall aim of the review is to highlight the importance of this rather poorly understood cell type and emphasize the need for further investigations into their angiogenic potential as an alternative source for therapeutic angiogenesis.

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

References

  1. Sherwood LM, Parris EE, Folkman J (1971) Tumor angiogenesis: therapeutic implications. N Engl J Med 285(21):1182–1186

    Google Scholar 

  2. Cao Y, Langer R (2008) A review of Judah Folkman’s remarkable achievements in biomedicine. Proc Natl Acad Sci 105(36):13203–13205

    CAS  PubMed  Google Scholar 

  3. Risau W (1997) Mechanisms of angiogenesis. Nature 386(6626):671–674

    CAS  PubMed  Google Scholar 

  4. Yin G, Liu W, An P, Li P, Ding I, Planelles V et al (2002) Endostatin gene transfer inhibits joint angiogenesis and pannus formation in inflammatory arthritis. Mol Ther 5(5):547–554

    CAS  PubMed  Google Scholar 

  5. Zhang H, van Olden C, Sweeney D, Martin-Rendon E (2014) Blood vessel repair and regeneration in the ischaemic heart. Open Heart 1(1):e000016

    PubMed  PubMed Central  Google Scholar 

  6. Laurenzana A, Fibbi G, Chillà A, Margheri G, Del Rosso T, Rovida E et al (2015) Lipid rafts: integrated platforms for vascular organization offering therapeutic opportunities. Cell Mol Life Sci 72(8):1537–1557

    CAS  PubMed  Google Scholar 

  7. Schipani E, Kronenberg HM (2008) Adult mesenchymal stem cells. In: StemBook [Internet]. Cambridge (MA): Harvard Stem Cell Institute. https://doi.org/10.3824/stembook.1.38.1. https://www.ncbi.nlm.nih.gov/books/NBK27056/

  8. Weissman IL, Anderson DJ, Gage F (2001) Stem and progenitor cells: origins, phenotypes, lineage commitments, and transdifferentiations. Annu Rev Cell Dev Biol 17(1):387–403

    CAS  PubMed  Google Scholar 

  9. Alviano F, Fossati V, Marchionni C, Arpinati M, Bonsi L, Franchina M et al (2007) Term Amniotic membrane is a high throughput source for multipotent Mesenchymal Stem Cells with the ability to differentiate into endothelial cells in vitro. BMC Dev Biol 21(7):11

    Google Scholar 

  10. Rae PC, Kelly RD, Egginton S, St John JC (2011) Angiogenic potential of endothelial progenitor cells and embryonic stem cells. Vasc Cell 3(1):11

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Lim R (2017) Concise review: fetal membranes in regenerative medicine: new tricks from an old dog?: fetal membranes in regenerative medicine. Stem Cells Transl Med 6(9):1767–1776

    PubMed  PubMed Central  Google Scholar 

  12. Parolini O, Alviano F, Bagnara GP, Bilic G, Bühring H-J, Evangelista M et al (2008) Concise review: isolation and characterization of cells from human term placenta: outcome of the first international workshop on placenta derived stem cells. Stem Cells 26(2):300–311

    PubMed  Google Scholar 

  13. in’t Anker PS, Scherjon SA, Kleijburg-van der Keur C, de Groot-Swings GMJS, Claas FHJ, Fibbe WE et al (2004) Isolation of mesenchymal stem cells of fetal or maternal origin from human placenta. Stem Cells 22(7):1338–1345

    Google Scholar 

  14. Schroeder DI, Blair JD, Lott P, Yu HOK, Hong D, Crary F et al (2013) The human placenta methylome. Proc Natl Acad Sci 110(15):6037–6042

    CAS  PubMed  Google Scholar 

  15. Castrechini NM, Murthi P, Gude NM, Erwich JJHM, Gronthos S, Zannettino A et al (2010) Mesenchymal stem cells in human placental chorionic villi reside in a vascular Niche. Placenta 31(3):203–212

    CAS  PubMed  Google Scholar 

  16. Chen C-Y, Liu S-H, Chen C-Y, Chen P-C, Chen C-P (2015) Human placenta-derived multipotent mesenchymal stromal cells involved in placental angiogenesis via the PDGF-BB and STAT3 pathways1. Biol Reprod 1(103):1–10

    Google Scholar 

  17. Demir R, Kaufmann P, Castellucci M, Erbengi T, Kotowski A (1989) Fetal vasculogenesis and angiogenesis in human placental villi. Acta Anat (Basel) 136(3):190–203

    CAS  Google Scholar 

  18. Pogozhykh O, Prokopyuk V, Figueiredo C, Pogozhykh D (2018) Placenta and placental derivatives in regenerative therapies: experimental studies, history, and prospects. Stem Cells Int 2018:1–14

    Google Scholar 

  19. Abumaree MH, Abomaray FM, Alshabibi MA, AlAskar AS, Kalionis B (2017) Immunomodulatory properties of human placental mesenchymal stem/stromal cells. Placenta 59:87–95

    CAS  PubMed  Google Scholar 

  20. Jaramillo-Ferrada PA, Wolvetang EJ, Cooper-White JJ (2012) Differential mesengenic potential and expression of stem cell-fate modulators in mesenchymal stromal cells from human-term placenta and bone marrow. J Cell Physiol 227(9):3234–3242

    CAS  PubMed  Google Scholar 

  21. Makhoul G, Chiu RCJ, Cecere R (2013) Placental mesenchymal stem cells: a unique source for cellular cardiomyoplasty. Ann Thorac Surg 95(5):1827–1833

    PubMed  Google Scholar 

  22. Chen C-Y, Tsai C-H, Chen C-Y, Wu Y-H, Chen C-P (2016) Human placental multipotent mesenchymal stromal cells modulate placenta angiogenesis through Slit2-Robo signaling. Cell Adhes Migr 10(1–2):66–76

    CAS  Google Scholar 

  23. Mathew SA, Chandravanshi B, Bhonde R (2017) Hypoxia primed placental mesenchymal stem cells for wound healing. Life Sci 182:85–92

    CAS  PubMed  Google Scholar 

  24. Kim MJ, Shin KS, Jeon JH, Lee DR, Shim SH, Kim JK et al (2011) Human chorionic-plate-derived mesenchymal stem cells and Wharton’s jelly-derived mesenchymal stem cells: a comparative analysis of their potential as placenta-derived stem cells. Cell Tissue Res 346(1):53–64

    PubMed  Google Scholar 

  25. Knöfler M, Haider S, Saleh L, Pollheimer J, Gamage TKJB, James J (2019) Human placenta and trophoblast development: key molecular mechanisms and model systems. Cell Mol Life Sci. https://doi.org/10.1007/s00018-019-03104-6

    Article  PubMed  PubMed Central  Google Scholar 

  26. Tamagawa T, Ishiwata I, Saito S (2004) Establishment and characterization of a pluripotent stem cell line derived from human amniotic membranes and initiation of germ layers in vitro. Hum Cell 17(3):125–130

    PubMed  Google Scholar 

  27. Moraghebi R, Kirkeby A, Chaves P, Rönn RE, Sitnicka E, Parmar M et al (2017) Term amniotic fluid: an unexploited reserve of mesenchymal stromal cells for reprogramming and potential cell therapy applications. Stem Cell Res Ther. https://doi.org/10.1186/s13287-017-0582-6

    Article  PubMed  PubMed Central  Google Scholar 

  28. Gonzalez AC, Costa TF, Andrade Z, Medrado ARAP (2016) Wound healing—a literature review. Anais Brasileiros de Dermatologia 91(5):614–620

    PubMed  PubMed Central  Google Scholar 

  29. Abumaree MH, Al Jumah MA, Kalionis B, Jawdat D, Al Khaldi A, AlTalabani AA et al (2013) Phenotypic and functional characterization of mesenchymal stem cells from chorionic villi of human term placenta. Stem Cell Rev Rep 9(1):16–31

    CAS  PubMed  Google Scholar 

  30. Mathew SA, Rajendran S, Gupta PK, Bhonde R (2013) Modulation of physical environment makes placental mesenchymal stromal cells suitable for therapy. Cell Biol Int 37(11):1197–1204

    CAS  PubMed  Google Scholar 

  31. Abomaray FM, Al Jumah MA, Alsaad KO, Jawdat D, Al Khaldi A, AlAskar AS et al (2016) Phenotypic and functional characterization of mesenchymal stem/multipotent stromal cells from Decidua Basalis of human term placenta. Stem Cells Int 2016:1–18

    Google Scholar 

  32. Ferraro F, Celso CL, Scadden D (2010) Adult stem cells and their niches. Adv Exp Med Biol 695:155–168

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Pereira RD, De Long NE, Wang RC, Yazdi FT, Holloway AC, Raha S (2015) Angiogenesis in the placenta: the role of reactive oxygen species signaling. Biomed Res Int 2015:1–12

    Google Scholar 

  34. Antoniadou E, David AL (2016) Placental stem cells. Best Pract Res Clin Obstetr Gynaecol 31:13–29

    Google Scholar 

  35. Abdulrazzak H, Moschidou D, Jones G, Guillot PV (2010) Biological characteristics of stem cells from foetal, cord blood and extraembryonic tissues. J R Soc Interface 7(Suppl 6):S689–S706

    PubMed  PubMed Central  Google Scholar 

  36. Barlow S, Brooke G, Chatterjee K, Price G, Pelekanos R, Rossetti T et al (2008) Comparison of human placenta- and bone marrow-derived multipotent mesenchymal stem cells. Stem Cells Dev 17(6):1095–1108

    CAS  PubMed  Google Scholar 

  37. Kusuma GD, Brennecke SP, O’Connor AJ, Kalionis B, Heath DE (2017) Decellularized extracellular matrices produced from immortal cell lines derived from different parts of the placenta support primary mesenchymal stem cell expansion. PLOS One 12(2):e0171488

    PubMed  PubMed Central  Google Scholar 

  38. Lee M-Y, Huang J-P, Chen Y-Y, Aplin JD, Wu Y-H, Chen C-Y et al (2009) Angiogenesis in differentiated placental multipotent mesenchymal stromal cells is dependent on integrin α5β1. PLoS One 4(10):e6913

    PubMed  PubMed Central  Google Scholar 

  39. Li G, Zhang X, Wang H, Wang X, Meng C, Chan C et al (2009) Comparative proteomic analysis of mesenchymal stem cells derived from human bone marrow, umbilical cord, and placenta: implication in the migration. Proteomics 9(1):20–30

    CAS  PubMed  Google Scholar 

  40. Kamprom W, Kheolamai P, U-Pratya Y, Supokawej A, Wattanapanitch M, Laowtammathron C et al (2016) Endothelial progenitor cell migration-enhancing factors in the secretome of placental-derived mesenchymal stem cells. Stem Cells Int 2016:1–13

    Google Scholar 

  41. Le Blanc K, Ringdén O (2005) Immunobiology of human mesenchymal stem cells and future use in hematopoietic stem cell transplantation. Biol Blood Marrow Transpl 11(5):321–334

    Google Scholar 

  42. Talwadekar MD, Kale VP, Limaye LS (2015) Placenta-derived mesenchymal stem cells possess better immunoregulatory properties compared to their cord-derived counterparts—a paired sample study. Sci Rep 5:15784

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Lee JM, Jung J, Lee H-J, Jeong SJ, Cho KJ, Hwang S-G et al (2012) Comparison of immunomodulatory effects of placenta mesenchymal stem cells with bone marrow and adipose mesenchymal stem cells. Int Immunopharmacol 13(2):219–224

    CAS  PubMed  Google Scholar 

  44. He S, Gleason J, Fik-Rymarkiewicz E, DiFiglia A, Bharathan M, Morschauser A et al (2017) Human placenta-derived mesenchymal stromal-like cells enhance angiogenesis via T cell-dependent reprogramming of macrophage differentiation: PDA-002 enhances angiogenesis via immunomodulation. Stem Cells 35(6):1603–1613

    CAS  PubMed  Google Scholar 

  45. Abumaree MH, Al Jumah MA, Kalionis B, Jawdat D, Al Khaldi A, Abomaray FM et al (2013) Human placental mesenchymal stem cells (pMSCs) play a role as immune suppressive cells by shifting macrophage differentiation from inflammatory M1 to anti-inflammatory M2 macrophages. Stem Cell Rev Rep 9:620–641

    CAS  PubMed  Google Scholar 

  46. Choi JH, Jung J, Na K-H, Cho KJ, Yoon TK, Kim GJ (2014) Effect of mesenchymal stem cells and extracts derived from the placenta on trophoblast invasion and immune responses. Stem Cells Dev 23(2):132–145

    CAS  PubMed  Google Scholar 

  47. Chang C-J, Yen M-L, Chen Y-C, Chien C-C, Huang H-I, Bai C-H et al (2006) Placenta-derived multipotent cells exhibit immunosuppressive properties that are enhanced in the presence of interferon-γ. Stem Cells 24(11):2466–2477

    CAS  PubMed  Google Scholar 

  48. Jones BJ, Brooke G, Atkinson K, McTaggart SJ (2007) Immunosuppression by placental indoleamine 2,3-dioxygenase: a role for mesenchymal stem cells. Placenta 28(11–12):1174–1181

    CAS  PubMed  Google Scholar 

  49. Selmani Z, Naji A, Zidi I, Favier B, Gaiffe E, Obert L et al (2008) Human leukocyte antigen-G5 secretion by human mesenchymal stem cells is required to suppress T lymphocyte and natural killer function and to induce CD4 CD25 FOXP3 regulatory T cells. Stem Cells 26:212–222

    CAS  PubMed  Google Scholar 

  50. Alshabibi MA, Khatlani T, Abomaray FM, AlAskar AS, Kalionis B, Messaoudi SA et al (2018) Human decidua basalis mesenchymal stem/stromal cells protect endothelial cell functions from oxidative stress induced by hydrogen peroxide and monocytes. Stem Cell Res Ther. https://doi.org/10.1186/s13287-018-1021-z

    Article  PubMed  PubMed Central  Google Scholar 

  51. Liao S, Zhang Y, Ting S, Zhen Z, Luo F, Zhu Z et al (2019) Potent immunomodulation and angiogenic effects of mesenchymal stem cells versus cardiomyocytes derived from pluripotent stem cells for treatment of heart failure. Stem Cell Res Ther 10(1):78

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Bianco P, Robey PG, Simmons PJ (2008) Mesenchymal stem cells: revisiting history, concepts, and assays. Cell Stem Cell 2(4):313–319

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Liang L, Li Z, Ma T, Han Z, Du W, Geng J et al (2017) Transplantation of human placenta-derived mesenchymal stem cells alleviates critical limb ischemia in diabetic nude rats. Cell Transpl 26(1):45–61

    Google Scholar 

  54. Meraviglia V, Vecellio M, Grasselli A, Baccarin M, Farsetti A, Capogrossi MC et al (2012) Human chorionic villus mesenchymal stromal cells reveal strong endothelial conversion properties. Differentiation 83(5):260–270

    CAS  PubMed  Google Scholar 

  55. Watt SM, Gullo F, van der Garde M, Markeson D, Camicia R, Khoo CP et al (2013) The angiogenic properties of mesenchymal stem/stromal cells and their therapeutic potential. Br Med Bull 108(1):25–53

    PubMed  PubMed Central  Google Scholar 

  56. Zahavi-Goldstein E, Blumenfeld M, Fuchs-Telem D, Pinzur L, Rubin S, Aberman Z et al (2017) Placenta-derived PLX-PAD mesenchymal-like stromal cells are efficacious in rescuing blood flow in hind limb ischemia mouse model by a dose- and site-dependent mechanism of action. Cytotherapy. https://doi.org/10.1016/j.jcyt.2017.09.010

    Article  PubMed  Google Scholar 

  57. Komaki M, Numata Y, Morioka C, Honda I, Tooi M, Yokoyama N et al (2017) Exosomes of human placenta-derived mesenchymal stem cells stimulate angiogenesis. Stem Cell Res Ther. https://doi.org/10.1186/s13287-017-0660-9

    Article  PubMed  PubMed Central  Google Scholar 

  58. Restrepo Y, Merle M, Petry D, Michon J (1985) Empty perineurial tube graft used to repair a digital nerve: a first case report. Microsurgery 6(2):73–77

    CAS  PubMed  Google Scholar 

  59. Clark D, Nakamura M, Miclau T, Marcucio R (2017) Effects of aging on fracture healing. Curr Osteoporos Rep 15:601. https://doi.org/10.1007/s11914-017-0413-9

    Article  PubMed  PubMed Central  Google Scholar 

  60. Liang T, Zhu L, Gao W, Gong M, Ren J, Yao H et al (2017) Coculture of endothelial progenitor cells and mesenchymal stem cells enhanced their proliferation and angiogenesis through PDGF and Notch signaling. FEBS Open Bio 7(11):1722–1736

    CAS  PubMed  PubMed Central  Google Scholar 

  61. DeCicco-Skinner KL, Henry GH, Cataisson C, Tabib T, Gwilliam JC, Watson NJ et al (2014) Endothelial cell tube formation assay for the in vitro study of angiogenesis. J Vis Exp 91:51312. https://doi.org/10.3791/51312

    Article  Google Scholar 

  62. König J, Weiss G, Rossi D, Wankhammer K, Reinisch A, Kinzer M et al (2015) Placental mesenchymal stromal cells derived from blood vessels or avascular tissues: what is the better choice to support endothelial cell function? Stem Cells Dev 24(1):115–131

    PubMed  Google Scholar 

  63. Cuiffo BG, Karnoub AE (2012) Mesenchymal stem cells in tumor development: emerging roles and concepts. Cell Adhes Migr 6(3):220–230

    Google Scholar 

  64. Makhoul G, Jurakhan R, Jaiswal PK, Ridwan K, Li L, Selvasandran K et al (2016) Conditioned medium of H9c2 triggers VEGF dependent angiogenesis by activation of p38/pSTAT3 pathways in placenta derived stem cells for cardiac repair. Life Sci 153:213–221

    CAS  PubMed  Google Scholar 

  65. Kadekar D, Rangole S, Kale V, Limaye L (2016) Conditioned medium from placental mesenchymal stem cells reduces oxidative stress during the cryopreservation of ex vivo expanded umbilical cord blood cells. PLOS One 11(10):e0165466

    PubMed  PubMed Central  Google Scholar 

  66. Prockop DJ (2007) “Stemness” does not explain the repair of many tissues by mesenchymal stem/multipotent stromal cells (MSCs). Clin Pharmacol Ther 82(3):241–243

    CAS  PubMed  Google Scholar 

  67. Caplan AI (2007) Adult mesenchymal stem cells for tissue engineering versus regenerative medicine. J Cell Physiol 213(2):341–347

    CAS  PubMed  Google Scholar 

  68. Yu B, Zhang X, Li X (2014) Exosomes derived from mesenchymal stem cells. Int J Mol Sci 15(3):4142–4157

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Phinney DG, Pittenger MF (2017) Concise review: MSC-derived exosomes for cell-free therapy: MSC-derived exosomes. Stem Cells 35(4):851–858

    CAS  PubMed  Google Scholar 

  70. Tooi M, Komaki M, Morioka C, Honda I, Iwasaki K, Yokoyama N et al (2016) Placenta mesenchymal stem cell derived exosomes confer plasticity on fibroblasts: a novel function of MSC-exosomes in vitro. J Cell Biochem 117(7):1658–1670

    CAS  PubMed  Google Scholar 

  71. Gong M, Yu B, Wang J, Wang Y, Liu M, Paul C et al (2017) Mesenchymal stem cells release exosomes that transfer miRNAs to endothelial cells and promote angiogenesis. Oncotarget. https://doi.org/10.18632/oncotarget.16778

    Article  PubMed  PubMed Central  Google Scholar 

  72. Hua Z, Lv Q, Ye W, Wong C-KA, Cai G, Gu D et al (2006) MiRNA-directed regulation of VEGF and other angiogenic factors under hypoxia. PLoS One 1(1):e116

    PubMed  PubMed Central  Google Scholar 

  73. Donker RB, Mouillet JF, Chu T, Hubel CA, Stolz DB, Morelli AE et al (2012) The expression profile of C19MC microRNAs in primary human trophoblast cells and exosomes. Mol Hum Reprod 18(8):417–424

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Delorme-Axford E, Donker RB, Mouillet J-F, Chu T, Bayer A, Ouyang Y et al (2013) Human placental trophoblasts confer viral resistance to recipient cells. Proc Natl Acad Sci 110(29):12048–12053

    CAS  PubMed  Google Scholar 

  75. Kuehbacher A, Urbich C, Dimmeler S (2008) Targeting microRNA expression to regulate angiogenesis. Trends Pharmacol Sci 29(1):12–15

    CAS  PubMed  Google Scholar 

  76. Liang X, Zhang L, Wang S, Han Q, Zhao RC (2016) Exosomes secreted by mesenchymal stem cells promote endothelial cell angiogenesis by transferring miR-125a. J Cell Sci 129(11):2182–2189

    CAS  PubMed  Google Scholar 

  77. Wang B, Jia H, Zhang B, Wang J, Ji C, Zhu X et al (2017) Pre-incubation with hucMSC-exosomes prevents cisplatin-induced nephrotoxicity by activating autophagy. Stem Cell Res Ther. https://doi.org/10.1186/s13287-016-0463-4

    Article  PubMed  PubMed Central  Google Scholar 

  78. Vizoso F, Eiro N, Cid S, Schneider J, Perez-Fernandez R (2017) Mesenchymal stem cell secretome: toward cell-free therapeutic strategies in regenerative medicine. Int J Mol Sci 18(9):1852

    PubMed Central  Google Scholar 

  79. Liang L (2019) Prenatal mesenchymal stem cell secretome and its clinical implication. In: Han ZC, Takahashi TA, Han Z, Li Z (eds) Perinatal stem cells. Springer, Singapore, pp 167–173. https://doi.org/10.1007/978-981-13-2703-2_13

    Chapter  Google Scholar 

  80. Marquez-Curtis LA, Janowska-Wieczorek A (2013) Enhancing the migration ability of mesenchymal stromal cells by targeting the SDF-1/CXCR80 axis. Biomed Res Int 2013:1–15

    Google Scholar 

  81. Stolzing A, Jones E, McGonagle D, Scutt A (2008) Age-related changes in human bone marrow-derived mesenchymal stem cells: consequences for cell therapies. Mech Ageing Dev 129(3):163–173

    CAS  PubMed  Google Scholar 

  82. Carmeliet P (2003) Angiogenesis in health and disease. Nat Med 9(6):653–660

    CAS  PubMed  Google Scholar 

  83. McBeath R, Pirone DM, Nelson CM, Bhadriraju K, Chen CS (2004) Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment. Dev Cell 6(4):483–495

    CAS  PubMed  Google Scholar 

  84. Pacini S, Petrini I (2014) Are MSCs angiogenic cells? New insights on human nestin-positive bone marrow-derived multipotent cells. Front Cell Dev Biol 2:20

    PubMed  PubMed Central  Google Scholar 

  85. Charnock-Jones DS (2016) Placental hypoxia, endoplasmic reticulum stress and maternal endothelial sensitisation by sFLT1 in pre-eclampsia. J Reprod Immunol 114:81–85

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Xu C, Li X, Guo P, Wang J (2017) Hypoxia-induced activation of JAK/STAT3 signaling pathway promotes trophoblast cell viability and angiogenesis in preeclampsia. Med Sci Monit 23:4909–4917

    PubMed  PubMed Central  Google Scholar 

  87. Li Y, Liu H, Cao L, Wu Y, Shi X, Qiao F et al (2017) Hypoxia downregulates the angiogenesis in human placenta via Notch1 signaling pathway. J Huazhong Univ Sci Technol [Medical Sciences] 37(4):541–546

    Google Scholar 

  88. Fujii T, Nagamatsu T, Morita K, Schust DJ, Iriyama T, Komatsu A et al (2017) Enhanced HIF2α expression during human trophoblast differentiation into syncytiotrophoblast suppresses transcription of placental growth factor. Sci Rep. https://doi.org/10.1038/s41598-017-12685-w

    Article  PubMed  PubMed Central  Google Scholar 

  89. de Oliveira LF, Almeida TR, Ribeiro Machado MP, Cuba MB, Alves AC, da Silva MV et al (2015) Priming mesenchymal stem cells with endothelial growth medium boosts stem cell therapy for systemic arterial hypertension. Stem Cells Int 2015:1–12

    Google Scholar 

  90. Mizukami T, Iso Y, Sato C, Sasai M, Spees JL, Toyoda M et al (2016) Priming with erythropoietin enhances cell survival and angiogenic effect of mesenchymal stem cell implantation in rat limb ischemia. Regener Ther 4:1–8

    Google Scholar 

  91. Mathew SA, Bhonde RR (2018) Omega-3 polyunsaturated fatty acids promote angiogenesis in placenta derived mesenchymal stromal cells. Pharmacol Res 132:90–98

    CAS  PubMed  Google Scholar 

  92. Wang J, Shi Y, Zhang L, Zhang F, Hu X, Zhang W et al (2014) Omega-3 polyunsaturated fatty acids enhance cerebral angiogenesis and provide long-term protection after stroke. Neurobiol Dis 68:91–103

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Hitzerd E, Broekhuizen M, Neuman RI, Colafella KMM, Merkus D, Schoenmakers S et al (2019) Human placental vascular reactivity in health and disease: implications for the treatment of pre-eclampsia. Curr Pharm Des 25(5):505–527

    CAS  PubMed  Google Scholar 

  94. Fuchi N, Miura K, Doi H, Li T-S, Masuzaki H (2017) Feasibility of placenta-derived mesenchymal stem cells as a tool for studying pregnancy-related disorders. Sci Rep 7:46220

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Kim J, Piao Y, Pak YK, Chung D, Han YM, Hong JS et al (2015) Umbilical cord mesenchymal stromal cells affected by gestational diabetes mellitus display premature aging and mitochondrial dysfunction. Stem Cells Dev 24(5):575–586

    CAS  PubMed  Google Scholar 

  96. Mathew SA, Bhonde R (2017) Mesenchymal stromal cells isolated from gestationally diabetic human placenta exhibit insulin resistance, decreased clonogenicity and angiogenesis. Placenta 59:1–8

    CAS  PubMed  Google Scholar 

  97. Francki A, Labazzo K, He S, Baum EZ, Abbot SE, Herzberg U et al (2016) Angiogenic properties of human placenta-derived adherent cells and efficacy in hindlimb ischemia. J Vasc Surg 64(3):746–756

    PubMed  Google Scholar 

  98. Xie N, Li Z, Adesanya TM, Guo W, Liu Y, Fu M et al (2016) Transplantation of placenta-derived mesenchymal stem cells enhances angiogenesis after ischemic limb injury in mice. J Cell Mol Med 20(1):29–37

    PubMed  Google Scholar 

  99. Alshareeda AT, Rakha E, Alghwainem A, Alrfaei B, Alsowayan B, Albugami A et al (2018) The effect of human placental chorionic villi derived mesenchymal stem cell on triple-negative breast cancer hallmarks. PLOS One 13(11):e0207593

    PubMed  PubMed Central  Google Scholar 

  100. Lee J-K, Park S-R, Jung B-K, Jeon Y-K, Lee Y-S, Kim M-K et al (2013) Exosomes derived from mesenchymal stem cells suppress angiogenesis by down-regulating VEGF expression in breast cancer cells. PLoS One 8(12):e84256

    PubMed  PubMed Central  Google Scholar 

  101. Zhang D, Zheng L, Shi H, Chen X, Wan Y, Zhang H et al (2014) Suppression of peritoneal tumorigenesis by placenta-derived mesenchymal stem cells expressing endostatin on colorectal cancer. Int J Med Sci 11(9):870–879

    CAS  PubMed  PubMed Central  Google Scholar 

  102. Kim K-S, Park J-M, Kong T, Kim C, Bae S-H, Kim HW et al (2016) Retinal angiogenesis effects of TGF-β1 and paracrine factors secreted from human placental stem cells in response to a pathological environment. Cell Transpl 25(6):1145–1157

    Google Scholar 

  103. Ji L, Zhang L, Li Y, Guo L, Cao N, Bai Z et al (2017) MiR-136 contributes to pre-eclampsia through its effects on apoptosis and angiogenesis of mesenchymal stem cells. Placenta 50:102–109

    CAS  PubMed  Google Scholar 

  104. Lazarus HM, Haynesworth SE, Gerson SL, Rosenthal NS, Caplan AI (1995) Ex vivo expansion and subsequent infusion of human bone marrow-derived stromal progenitor cells (mesenchymal progenitor cells): implications for therapeutic use. Bone Marrow Transpl 16(4):557–564

    CAS  Google Scholar 

  105. Prather WR, Toren A, Meiron M, Ofir R, Tschope C, Horwitz EM (2009) The role of placental-derived adherent stromal cell (PLX-PAD) in the treatment of critical limb ischemia. Cytotherapy 11(4):427–434

    CAS  PubMed  Google Scholar 

  106. Kadekar D, Kale V, Limaye L (2015) Differential ability of MSCs isolated from placenta and cord as feeders for supporting ex vivo expansion of umbilical cord blood derived CD34 + cells. Stem Cell Res Ther 6:201

    PubMed  PubMed Central  Google Scholar 

  107. Du W, Li X, Chi Y, Ma F, Li Z, Yang S et al (2016) VCAM-1 + placenta chorionic villi-derived mesenchymal stem cells display potent pro-angiogenic activity. Stem Cell Res Ther 7:49

    PubMed  PubMed Central  Google Scholar 

  108. Heazlewood CF, Sherrell H, Ryan J, Atkinson K, Wells CA, Fisk NM (2014) High incidence of contaminating maternal cell overgrowth in human placental mesenchymal stem/stromal cell cultures: a systematic review: maternal contamination in placental MSCs: a review. Stem Cells Transl Med 3(11):1305–1311

    PubMed  PubMed Central  Google Scholar 

  109. Sardesai VS, Shafiee A, Fisk NM, Pelekanos RA (2017) Avoidance of maternal cell contamination and overgrowth in isolating fetal chorionic villi mesenchymal stem cells from human term placenta: determinants of pure feto-placental MSC isolation. Stem Cells Transl Med 6(4):1070–1084

    CAS  PubMed  PubMed Central  Google Scholar 

  110. Mathews S, Lakshmi Rao K, Suma Prasad K, Kanakavalli MK, Govardhana Reddy A, Avinash Raj T et al (2015) Propagation of pure fetal and maternal mesenchymal stromal cells from terminal chorionic villi of human term placenta. Sci Rep 5:10054

    CAS  PubMed  PubMed Central  Google Scholar 

  111. Alrefaei GI, Al-Karim S, Ayuob NN, Ali SS (2015) Does the maternal age affect the mesenchymal stem cell markers and gene expression in the human placenta? What is the evidence? Tissue Cell 47(4):406–419

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors wish to thank the Vice-Chancellor and Registrar, Manipal Academy of Higher Education, India, for extending all the facilities needed to carry out the present work. We would also like to thank Dr. Gopal Pande, Dean SORM, for his continuous guidance and support and Mr. Febin Varghese for his contribution to the graphic work.

Author information

Authors and Affiliations

  1. School of Regenerative Medicine, Manipal Academy of Higher Education, MAHE, Allalasandra, Near Royal Orchid, Yellahanka, Bangalore, 560 065, India

    Suja Ann Mathew & Charuta Naik

  2. School of Biotechnology, Faculty of Science and Health, Dublin City University, Glasnevin Dublin 9, Ireland

    Paul A. Cahill

  3. Dr. D.Y. Patil Vidyapeeth (DPU), Pimpri, Pune, 411018, India

    Ramesh R. Bhonde

Authors
  1. Suja Ann Mathew
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Charuta Naik
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Paul A. Cahill
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ramesh R. Bhonde
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Suja A. Mathew: conceived, designed and wrote the paper; Charuta Naik: collected the data and prepared the image; Paul A. Cahill: critical editing and writing of the paper; Ramesh Bhonde: designed and critical editing of the paper.

Corresponding authors

Correspondence to Suja Ann Mathew or Ramesh R. Bhonde.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest in their study.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mathew, S.A., Naik, C., Cahill, P.A. et al. Placental mesenchymal stromal cells as an alternative tool for therapeutic angiogenesis. Cell. Mol. Life Sci. 77, 253–265 (2020). https://doi.org/10.1007/s00018-019-03268-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00018-019-03268-1

Keywords

Search

Navigation