Abstract
Cardiovascular diseases are the main cause of death in the world. Despite the extensive progress of conventional medicine in disease treatment, a large number of patients are suffering from civilization diseases, and there is still a need to develop more effective therapies. A developing field in cardiovascular therapy is the use of a certain population of mesenchymal stem cells, specifically those defined as “perinatal” derived from tissue related to pregnancy and child delivery. Perinatal stem cells may be promising in view of higher proliferative potential, their well-documented cell multipotency, paracrine effect, immunomodulatory properties, low immunogenicity, and also safety while sourcing. Moreover, perinatal MSCs do not impose any ethical concerns. Thanks to these features and functions, MSCs have become widely used in allogeneic transplantation in recent years. In point of fact, these characteristics are the reason why perinatal MSCs have quickly become ideal “off-the-shelf” medical products. A number of animal models of cell therapy for human diseases and several clinical studies have shown the safety and effectiveness of such therapy. This chapter reviews the current knowledge about perinatal MSCs in terms of their therapeutic potential, clinical effects, and safety in clinical applications.
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Abbreviations
- ADM:
-
Adrenomedullin
- AF-MSCs:
-
Amniotic fluid-derived mesenchymal stem cells
- AMI:
-
Acute myocardial infarction
- Ang-1:
-
Angiopoietin-1
- ATMPs:
-
Advanced therapy medicinal products
- bFGF:
-
Basic fibroblast growth factor
- BMP-2:
-
Bone morphogenetic protein-2
- CAM:
-
Cell adhesion molecule
- CCR:
-
C-C chemokine receptor
- CMCs:
-
Cardiomyocyte cells
- CXCR:
-
CXC chemokine receptor
- ECM:
-
Extracellular matrix
- ECs:
-
Endothelial cells
- EGF:
-
Epidermal growth factor
- EMA:
-
European Medicines Agency
- EPO:
-
Erythropoietin
- EVs:
-
Extracellular vesicles
- FGF-2:
-
Fibroblast growth factor-2
- GCP:
-
Good clinical practice
- G-CSF:
-
Granulocyte colony-stimulating factor
- GMP:
-
Good manufacturing practice
- HGF:
-
Hepatocyte growth factor
- HIF-1α:
-
Hypoxia-inducible factor 1α
- HLA:
-
Human leukocyte antigens
- ICAM-1:
-
Intercellular adhesion molecule-1
- IGF-1:
-
Insulin-like growth factor-1
- IHD:
-
Ischemic heart disease
- IL-10:
-
Interleukin-10
- IL-1β:
-
Interleukin-1β
- IL-3:
-
Interleukin-3
- IL-4:
-
Interleukin-4
- IL-6:
-
Interleukin-6
- IL-8:
-
Interleukin-8
- ISCT:
-
International Society for Cellular Therapy
- LV:
-
Left ventricle
- LVEF:
-
Left ventricle ejection fraction
- MCP-1:
-
Monocyte chemoattractant protein-1
- MHC II:
-
Major histocompatibility complex class II
- MIP-1α:
-
Macrophage inflammatory proteins-1α
- MMIF:
-
Macrophage migration inhibitory factor
- MMP-1:
-
Matrix metalloproteinase 1
- MMP-2:
-
Matrix metalloproteinase 2
- MMP-9:
-
Matrix metalloproteinase 9
- MSCs:
-
Mesenchymal stem cells
- PAI-1:
-
Plasminogen activator inhibitor-1
- PDGF:
-
Platelet-derived growth factor
- PGE2:
-
Prostaglandin E2
- PGF:
-
Prostaglandin F
- PIGF:
-
Placental growth factor
- P-MSCs:
-
Placenta-derived mesenchymal stem cells
- SCF:
-
Stem cell factor
- SDF-1:
-
Stromal cell-derived factor-1
- sFRP-2:
-
Secreted frizzled-related protein-2
- TGF-β1:
-
Transforming growth factor-β1
- TIMP-1:
-
Tissue inhibitor of metalloproteinase-1
- TIMP-2:
-
Tissue inhibitor of metalloproteinase-2
- TIMP-9:
-
Tissue inhibitor of metalloproteinase-9
- TNF-α:
-
Tumor necrosis factor-α
- TSP-1:
-
Thrombospondin 1
- UC-MSCs:
-
Umbilical cord-derived mesenchymal stem cells
- VCAM-1:
-
Vascular cell adhesion molecule-1
- VEGF:
-
Vascular endothelial growth factor
- VLA-4:
-
Very late antigen-4
- VSMCs:
-
Vascular smooth muscle cells
- WJ-MSCs:
-
Wharton’s jelly-derived mesenchymal stem cells
References
Abumaree MH, Abomaray FM, Alshabibi MA, AlAskar AS, Kalionis B (2017) Immunomodulatory properties of human placental mesenchymal stem/stromal cells. Placenta 59:87–95. https://doi.org/10.1016/j.placenta.2017.04.003
Afzal MR, Samanta A, Shah ZI, Jeevanantham V, Abdel-Latif A, Zuba-Surma EK, Dawn B (2015) Adult bone marrow cell therapy for ischemic heart disease: evidence and insights from randomized controlled trials. Circ Res 117(6):558–575. https://doi.org/10.1161/CIRCRESAHA.114.304792
Amable PR, Teixeira MVT, Carias RBV, Granjeiro JM, Borojevic R (2014) Protein synthesis and secretion in human mesenchymal cells derived from bone marrow, adipose tissue and Wharton’s jelly. Stem Cell Res Ther 5(2):53. https://doi.org/10.1186/scrt442
Anderson JD, Johansson HJ, Graham CS, Vesterlund M, Pham MT, Bramlett CS, Montgomery EN, Mellema MS, Bardini RL, Contreras Z, Hoon M, Bauer G, Fink KD, Fury B, Hendrix KJ, Chedin F, El-Andaloussi S, Hwang B, Mulligan MS, Lehtiö J, Nolta JA (2016) Comprehensive proteomic analysis of mesenchymal stem cell exosomes reveals modulation of angiogenesis via nuclear factor-kappaB signaling. Stem Cells 34(3):601–613. https://doi.org/10.1002/stem.2298
Arutyunyan I, Fatkhudinov T, Kananykhina E, Usman N, Elchaninov A, Makarov A, Bolshakova G, Goldshtein D, Sukhikh G (2016) Role of VEGF-A in angiogenesis promoted by umbilical cord-derived mesenchymal stromal/stem cells: in vitro study. Stem Cell Res Ther 7:46. https://doi.org/10.1186/s13287-016-0305-4
Bagno L, Hatzistergos KE, Balkan W, Hare JM (2018) Mesenchymal stem cell-based therapy for cardiovascular disease: progress and challenges. Mol Ther 26(7):1610–1623
Bartolucci J, Verdugo FJ, González PL, Larrea RE, Abarzua E, Goset C, Rojo P, Palma I, Lamich R, Pedreros PA, Valdivia G, Lopez VM, Nazzal C, Alcayaga-Miranda F, Cuenca J, Brobeck MJ, Patel AN, Figueroa FE, Khoury M (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 [Randomized clinical trial of intravenous infusion umbilical cord mesenchymal stem cells on cardiopathy]). Circ Res 121(10):1192–1204. https://doi.org/10.1161/CIRCRESAHA.117.310712
Batsali K, Kastrinaki M-C, Papadaki H, Pontikoglou C (2013) Mesenchymal stem cells derived from Wharton’s jelly of the umbilical cord: biological properties and emerging clinical applications. Curr Stem Cell Res Ther 8(2):144–155. https://doi.org/10.2174/1574888x11308020005
Benjamin EJ, Muntner P, Alonso A, Bittencourt MS, Callaway CW, Carson AP, Chamberlain AM, Chang AR, Cheng S, Das SR, Delling FN, Djousse L, Elkind MSV, Ferguson JF, Fornage M, Jordan LC, Khan SS, Kissela BM, Knutson KL, Kwan TW, Lackland DT, Lewis TT, Lichtman JH, Longenecker CT, Loop MS, Lutsey PL, Martin SS, Matsushita K, Moran AE, Mussolino ME, O’Flaherty M, Pandey A, Perak AM, Rosamond WD, Roth GA, Sampson UKA, Satou GM, Schroeder EB, Shah SH, Spartano NL, Stokes A, Tirschwell DL, Tsao CW, Turakhia MP, VanWagner LB, Wilkins JT, Wong SS, Virani SS (2019) Heart disease and stroke statistics-2019 update: a report from the American Heart Association. Circulation 139(10):e56–e528. https://doi.org/10.1161/CIR.0000000000000659
Berebichez-Fridman R, Montero-Olvera PR (2018) Sources and clinical applications of mesenchymal stem cells state-of-the-art review. Sultan Qaboos Univ Med J 18(3):e264–e277. https://doi.org/10.18295/squmj.2018.18.03.002
Bernardo ME, Fibbe WE (2013) Mesenchymal stromal cells: sensors and switchers of inflammation. Cell Stem Cell 13(4):392–402
Bobis-Wozowicz S, Miekus K, Wybieralska E, Jarocha D, Zawisz A, Madeja Z, Majka M (2011) Genetically modified adipose tissue-derived mesenchymal stem cells overexpressing CXCR4 display increased motility, invasiveness, and homing to bone marrow of NOD/SCID mice. Exp Hematol 39(6):686–696.e4. https://doi.org/10.1016/j.exphem.2011.03.004
Bongso A, Fong CY (2013) The therapeutic potential, challenges and future clinical directions of stem cells from the Wharton’s Jelly of the human umbilical cord. Stem Cell Rev Rep 9(2):226–240. https://doi.org/10.1007/s12015-012-9418-z
Boráň T, Menezes-Ferreira M, Reischl I, Celis P, Ferry N, Gänsbacher B, Krafft H, Lipucci di Paola M, Sladowski D, Salmikangas P (2017) Clinical development and commercialization of advanced therapy medicinal products in the european union: how are the product pipeline and regulatory framework evolving? Hum Gene Ther Clin Dev 28(3):126–135. https://doi.org/10.1089/humc.2016.193
Borys-Wójcik S, Brązert M, Jankowski M, Ożegowska K, Chermuła B, Piotrowska-Kempisty H, Bukowska D, Antosik P, Pawelczyk L, Nowicki M, Jeseta M, Kempisty B (2019) Human Wharton’s jelly mesenchymal stem cells: properties, isolation and clinical applications. J Biol Regul Homeost Agents 33(1):119–123
Brychtova M, Thiele JA, Lysak D, Holubova M, Kralickova M, Vistejnova L (2019) Mesenchymal stem cells as the near future of cardiology medicine—truth or wish? Biomed Pap 163(1):8–18. https://doi.org/10.5507/bp.2018.071
Can A, Celikkan FT, Cinar O (2017) Umbilical cord mesenchymal stromal cell transplantations: a systemic analysis of clinical trials. Cytotherapy 19(12):1351–1382
Caplan AI (2018) Cell-based therapies: the nonresponder. Stem Cells Transl Med 7:762–766. https://doi.org/10.1002/sctm.18-0074
Chen H-J, Chen C-H, Chang M-Y, Tsai D-C, Baum EZ, Hariri R, Herzberg U, Hsieh PCH (2015) Human placenta-derived adherent cells improve cardiac performance in mice with chronic heart failure. Stem Cells Transl Med 4(3):269–275. https://doi.org/10.5966/sctm.2014-0135
Choi YS, Dusting GJ, Stubbs S, Arunothayaraj S, Han XL, Collas P, Morrison WA, Dilley RJ (2010) Differentiation of human adipose-derived stem cells into beating cardiomyocytes. J Cell Mol Med 14(4):878–889. https://doi.org/10.1111/j.1582-4934.2010.01009.x
Constantinescu A, Andrei E, Iordache F, Buzila C, Maniu H (2013) Human fetal stem cells differentiation and plasticity potential. Ann Rom Soc Cell Biol 18(2):16–27
De Coppi P, Bartsch G, Siddiqui MM, Xu T, Santos CC, Perin L, Mostoslavsky G, Serre AC, Snyder EY, Yoo JJ, Furth ME, Soker S, Atala A (2007) Isolation of amniotic stem cell lines with potential for therapy. Nat Biotechnol 25(1):100–106. https://doi.org/10.1038/nbt1274
Deng Y, Zhang Y, Ye L, Zhang T, Cheng J, Chen G, Zhang Q, Yang Y (2016) Umbilical cord-derived mesenchymal stem cells instruct monocytes towards an IL10-producing phenotype by secreting IL6 and HGF. Sci Rep 6:37566. https://doi.org/10.1038/srep37566
Di Trapani M, Bassi G, Ricciardi M, Fontana E, Bifari F, Pacelli L, Giacomello L, Pozzobon M, Féron F, De Coppi P, Anversa P, Fumagalli G, Decimo I, Menard C, Tarte K, Krampera M (2013) Comparative study of immune regulatory properties of stem cells derived from different tissues. Stem Cells Dev 22(22):2990–3002. https://doi.org/10.1089/scd.2013.0204
Ding DC, Chou HL, Chang YH, Hung WT, Liu HW, Chu TY (2016) Characterization of HLA-G and related immunosuppressive effects in human umbilical cord stroma-derived stem cells. Cell Transplant 25:217–228. https://doi.org/10.3727/096368915X688182
Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Deans R, Keating A, Prockop D, Horwitz E (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8(4):315–317. https://doi.org/10.1080/14653240600855905
Drozdz T, Debicka-Dabrowska D, Styczkiewicz K, Czarnecka D, Kawecka-Jaszcz K (2014) New non-pharmacological treatment methods in heart failure. Przegl Lek 71(8):441–446
Eseonu OI, De Bari C (2015) Homing of mesenchymal stem cells: mechanistic or stochastic? Implications for targeted delivery in arthritis. Rheumatology 54(2):210–218
Fanchin R, Gallot V, Rouas-Freiss N, Frydman R, Carosella ED (2007) Implication of HLA-G in human embryo implantation. Hum Immunol 68(4):259–263. https://doi.org/10.1016/j.humimm.2006.11.002
Friedenstein AJ, Chailakhjan RK, Lalykina KS (1970) The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells. Cell Prolif 3(4):393–403. https://doi.org/10.1111/j.1365-2184.1970.tb00347.x
Gao LR, Chen Y, Zhang NK, Yang XL, Liu HL, Wang ZG, Yan XY, Wang Y, Zhu ZM, Li TC, Wang LH, Chen HY, Chen YD, Huang CL, Qu P, Yao C, Wang B, Chen GH, Wang ZM, Xu ZY, Bai J, Lu D, Shen YH, Guo F, Liu MY, Yang Y, Ding YC, Yang Y, Tian HT, Ding QA, Li LN, Yang XC, Hu X (2015) Intracoronary infusion of Wharton’s jelly-derived mesenchymal stem cells in acute myocardial infarction: double-blind, randomized controlled trial. BMC Med 13:162. https://doi.org/10.1186/s12916-015-0399-z
Gapska P, Kurpisz M (2017) Perspective in optimization of stem cell therapies for heart regeneration. Postepy Hig Med Dosw 71:975–987. https://doi.org/10.5604/01.3001.0010.6665
Ghafarzadeh M, Namdari M, Eatemadi A (2016) Stem cell therapies for congenital heart disease. Biomed Pharmacother 84:1163–1171
Gnecchi M, Cervio E (2013) Mesenchymal stem cell therapy for heart disease. Vascul Pharmacol 57(1):48–55
Hamid T, Prabhu SD (2017) Immunomodulation is the key to cardiac repair. Circ Res 20(10):1530–1532. https://doi.org/10.1161/circresaha.117.310954
Hare JM, Fishman JE, Gerstenblith G, DiFede Velazquez DL, Zambrano JP, Suncion VY, Tracy M, Ghersin E, Johnston PV, Brinker JA, Breton E, Davis-Sproul J, Schulman IH, Byrnes J, Mendizabal AM, Lowery MH, Rouy D, Altman P, Wong Po Foo C, Ruiz P, Amador A, Da Silva J, McNiece IK, Heldman AW (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):2369–2379. https://doi.org/10.1001/jama.2012.25321
Henning RJ, Burgos JD, Ondrovic L, Sanberg P, Balis J, Morgan MB (2006) Human umbilical cord blood progenitor cells are attracted to infarcted myocardium and significantly reduce myocardial infarction size. Cell Transplant 15(7):647–658. https://doi.org/10.3727/000000006783981611
Henning RJ, Shariff M, Eadula U, Alvarado F, Vasko M, Sanberg PR, Sanberg CD, Delostia V (2008) Human cord blood mononuclear cells decrease cytokines and inflammatory cells in acute myocardial infarction. Stem Cells Dev. https://doi.org/10.1089/scd.2008.0023
Honczarenko M, Le Y, Swierkowski M, Ghiran I, Glodek AM, Silberstein LE (2005) Human bone marrow stromal cells express a distinct set of biologically functional chemokine receptors. Stem Cells 24(4):1030–1041. https://doi.org/10.1634/stemcells.2005-0319
In ’t Anker PS, Scherjon SA, Kleijburg-van der Keur C, Noort WA, FHJ C, Willemze R, Fibbe WE, HHH K (2003) Amniotic fluid as a novel source of mesenchymal stem cells for therapeutic transplantation. Blood 102(4):1548–1549. https://doi.org/10.1182/blood-2003-04-1291
In ’t Anker PS, Scherjon SA, Kleijburg-van der Keur C, de Groot-Swings GMJS, Claas FHJ, Fibbe WE, Kanhai HHH (2004) Isolation of mesenchymal stem cells of fetal or maternal origin from human placenta. Stem Cells 22(7):1338–1345. https://doi.org/10.1634/stemcells.2004-0058
Ip JE, Wu Y, Huang J, Zhang L, Pratt RE, Dzau VJ (2007) Mesenchymal stem cells use integrin β1 not CXC chemokine receptor 4 for myocardial migration and engraftment. Mol Biol Cell 18(8):2873–2882. https://doi.org/10.1091/mbc.E07-02-0166
Kia NA, Bahrami AR, Ebrahimi M, Matin MM, Neshati Z, Almohaddesin MR, Aghdami N, Bidkhori HR (2011) Comparative analysis of chemokine receptor’s expression in mesenchymal stem cells derived from human bone marrow and adipose tissue. J Mol Neurosci 44(3):178–185. https://doi.org/10.1007/s12031-010-9446-6
Kim YS (2009) TNF-alpha enhances engraftment of mesenchymal stem cells into infarcted myocardium. Front Biosci 14:2845–2856. https://doi.org/10.2741/3417
Kim YJ, Broxmeyer HE (2011) Immune regulatory cells in umbilical cord blood and their potential roles in transplantation tolerance. Crit Rev Oncol Hematol 79(12):112–126
Kim DW, Staples M, Shinozuka K, Pantcheva P, Kang SD, Borlongan CV (2013) Wharton’s jelly-derived mesenchymal stem cells: phenotypic characterization and optimizing their therapeutic potential for clinical applications. Int J Mol Sci 14(6):11692–11712
Kim SH, Cho JH, Lee YH, Lee JH, Kim SS, Kim MY, Lee MG, Kang WY, Lee KS, Ahn YK, Jeong MH, Kim HS (2018) Improvement in left ventricular function with intracoronary mesenchymal stem cell therapy in a patient with anterior wall ST-segment elevation myocardial infarction. Cardiovasc Drugs Ther 32:329–338. https://doi.org/10.1007/s10557-018-6804-z
Krampera M, Galipeau J, Shi Y, Tarte K, Sensebe L (2013) Immunological characterization of multipotent mesenchymal stromal cells—the international society for cellular therapy (ISCT) working proposal. Cytotherapy 15(9):1054–1061. https://doi.org/10.1016/j.jcyt.2013.02.010
Kwiecien E, Drabik L, Mazurek A, Urbanczyk M, Szot W, Kostkiewicz M, Banys RP, Brzyszczyk-Marzec M, Czyz L, Kozynacka A, Plazak W, Olszowska M, Majka M, Podolec P, Musialek P (2019) P4604Insights into left ventricular remodelling and clinical outcomes after Wharton’s jelly multipotent stem cells transcoronary administration in a pilot cohort of CIRCULATE-AMI trial (NCT03404063). Eur Heart J. https://doi.org/10.1093/eurheartj/ehz745.0987
Kyurkchiev D (2014) Secretion of immunoregulatory cytokines by mesenchymal stem cells. World J Stem Cells 6(5):552–570. https://doi.org/10.4252/wjsc.v6.i5.552
Lalu MM, Mazzarello S, Zlepnig J, Yuan Yi Ryan D, Montroy J, McIntyre L, Devereaux PJ, Stewart DJ, David Mazer C, Barron CC, Mcisaac DI, Fergusson DA (2018) Safety and efficacy of adult stem cell therapy for acute myocardial infarction and ischemic heart failure (SafeCell heart): a systematic review and meta-analysis. Stem Cells Transl Med 7(12):857–866
Lee JW, Lee SH, Youn YJ, Ahn MS, Kim JY, Yoo BS, Yoon J, Kwon W, Hong IS, Lee K, Kwan J, Park KS, Choi D, Jang YS, Hong MK (2014) A randomized, open-label, multicenter trial for the safety and efficacy of adult mesenchymal stem cells after acute myocardial infarction. J Korean Med Sci 29(1):23–31. https://doi.org/10.3346/jkms.2014.29.1.23
Lelek J, Zuba-Surma EK (2020) Perspectives for future use of extracellular vesicles from umbilical cord-and adipose tissue-derived mesenchymal stem/stromal cells in regenerative therapies—synthetic review. Int J Mol Sci 21(3):799
Li X, Hu Y, Guo Y, Chen Y, Guo D, Zhou H, Zhang F, Zhao Q (2015) Safety and efficacy of intracoronary human umbilical cord-derived mesenchymal stem cell treatment for very old patients with coronary chronic total occlusion. Curr Pharm Des 21(11):1426–1432. https://doi.org/10.2174/1381612821666141126100636
Liu B, Duan CY, Luo CF, Ou CW, Sun K, Wu ZY, Huang H, Cheng CF, Li YP, Chen MS (2014a) Effectiveness and safety of selected bone marrow stem cells on left ventricular function in patients with acute myocardial infarction: a meta-analysis of randomized controlled trials. Int J Cardiol 177(3):764–770
Liu K, Ji K, Guo L, Wu W, Lu H, Shan P, Yan C (2014b) Mesenchymal stem cells rescue injured endothelial cells in an in vitro ischemia-reperfusion model via tunneling nanotube like structure-mediated mitochondrial transfer. Microvasc Res 92:10–18. https://doi.org/10.1016/j.mvr.2014.01.008
Lu LL, Liu YJ, Yang SG, Zhao QJ, Wang X, Gong W, Han ZB, Xu ZS, Lu YX, Liu D, Chen ZZ, Han ZC (2006) Isolation and characterization of human umbilical cord mesenchymal stem cells with hematopoiesis-supportive function and other potentials. Haematologica 91(8):1017–1026
Lupu M, Khalil M, Andrei E, Iordache F, Pfannkuche K, Neef K, Georgescu A, Buzila C, Brockmeier K, Maniu H, Hescheler J (2011) Integration properties of Wharton’s jelly-derived novel mesenchymal stem cells into ventricular slices of murine hearts. Cell Physiol Biochem 28(1):63–76. https://doi.org/10.1159/000331714
Lüttichau IV, Notohamiprodjo M, Wechselberger A, Peters C, Henger A, Seliger C, Djafarzadeh R, Huss R, Nelson PJ (2005) Human adult CD34−progenitor cells functionally express the chemokine receptors CCR1, CCR4, CCR7, CXCR5, and CCR10 but Not CXCR4. Stem Cells Dev 14(3):329–336. https://doi.org/10.1089/scd.2005.14.329
Maciulaitis R, D’Apote L, Buchanan A, Pioppo L, Schneider CK (2012) Clinical development of advanced therapy medicinal products in europe: evidence that regulators must be proactive. Mol Ther 20(3):479–482. https://doi.org/10.1038/mt.2012.13
Magatti M, De Munari S, Vertua E, Gibelli L, Wengler GS, Parolini O (2008) Human amnion mesenchyme harbors cells with allogeneic T-cell suppression and stimulation capabilities. Stem Cells 26(1):182–192. https://doi.org/10.1634/stemcells.2007-0491
Magatti M, De Munari S, Vertua E, Nassauto C, Albertini A, Wengler GS, Parolini O (2009) Amniotic mesenchymal tissue cells inhibit dendritic cell differentiation of peripheral blood and amnion resident monocytes. Cell Transplant 18(8):899–914. https://doi.org/10.3727/096368909X471314
Majka M, Sułkowski M, Badyra B, Musiałek P (2017) Concise review: mesenchymal stem cells in cardiovascular regeneration: emerging research directions and clinical applications. Stem Cells Transl Med 6(10):1859–1867
Makino S, Fukuda K, Miyoshi S, Konishi F, Kodama H, Pan J, Sano M, Takahashi T, Hori S, Abe H, Hata JI, Umezawa A, Ogawa S (1999) Cardiomyocytes can be generated from marrow stromal cells in vitro. J Clin Invest 103(5):697–705. https://doi.org/10.1172/JCI5298
Martinez EC, Vu DT, Wang J, Lilyanna S, Ling LH, Gan SU, Tan AL, Phan TT, Lee CN, Kofidis T (2013) Grafts enriched with subamnion-cord-lining mesenchymal stem cell angiogenic spheroids induce post-ischemic myocardial revascularization and preserve cardiac function in failing rat hearts. Stem Cells Dev 22(23):3087–3099. https://doi.org/10.1089/scd.2013.0119
Martins JP, Santos JM, Almeida JM, De Filipe MA, De Almeida MVT, Almeida SCP, Água-Doce A, Varela A, Gilljam M, Stellan B, Pohl S, Dittmar K, Lindenmaier W, Alici E, Graça L, Cruz PE, Cruz HJ, Bárcia RN (2014) Towards an advanced therapy medicinal product based on mesenchymal stromal cells isolated from the umbilical cord tissue: quality and safety data. Stem Cell Res Ther 5(1):9. https://doi.org/10.1186/scrt398
Mirabella T, Hartinger J, Lorandi C, Gentili C, Van Griensven M, Cancedda R (2012) Proangiogenic soluble factors from amniotic fluid stem cells mediate the recruitment of endothelial progenitors in a model of ischemic fasciocutaneous flap. Stem Cells Dev 21(12):2179–2188. https://doi.org/10.1089/scd.2011.0639
Mirotsou M, Zhang Z, Deb A, Zhang L, Gnecchi M, Noiseux N, Mu H, Pachori A, Dzau V (2007) Secreted frizzled related protein 2 (Sfrp2) is the key Akt-mesenchymal stem cell-released paracrine factor mediating myocardial survival and repair. Proc Natl Acad Sci U S A 104(5):1643–1648. https://doi.org/10.1073/pnas.0610024104
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(4):459–465. https://doi.org/10.1038/nm1391
Moll G, Ankrum JA, Kamhieh-Milz J, Bieback K, Ringdén O, Volk HD, Geissler S, Reinke P (2019) Intravascular mesenchymal stromal/stem cell therapy product diversification: time for new clinical guidelines. Trends Mol Med 25(2):149–163
Murray IR, West CC, Hardy WR, James AW, Park TS, Nguyen A, Tawonsawatruk T, Lazzari L, Soo C, Péault B (2014) Natural history of mesenchymal stem cells, from vessel walls to culture vessels. Cell Mol Life Sci 71(8):1353–1374
Musialek P, Mazurek A, Jarocha D, Tekieli L, Szot W, Kostkiewicz M, Banys RP, Urbanczyk M, Kadzielski A, Trystula M, Kijowski J, Zmudka K, Podolec P, Majka M (2015) Myocardial regeneration strategy using Wharton’s jelly mesenchymal stem cells as an off-the-shelf “unlimited” therapeutic agent: results from the acute myocardial infarction first-in-man study. Postepy Kardiol Interwencyjnej 11(2):100–107. https://doi.org/10.5114/pwki.2015.52282
Musialek P, Mazurek A, Kwiecien E, Drabik L, Tekieli L, Szot W, Kostkiewicz M, Jarocha D, Banys RP, Urbanczyk M, Plazak W, Olszowska M, Zmudka K, Podolec P, Majka M (2017) P4027Safety and high-grade myocardial uptake of Whartons Jelly plurioptent stem cells transcoronary transfer in acute myocardial infarction in man. Eur Heart J 38:ehx504. https://doi.org/10.1093/eurheartj/ehx504.p4027
Nagamura-Inoue T (2014) Umbilical cord-derived mesenchymal stem cells: their advantages and potential clinical utility. World J Stem Cells 6(2):195–202. https://doi.org/10.4252/wjsc.v6.i2.195
Noriega DC, Ardura F, Hernández-Ramajo R, Martín-Ferrero MÁ, Sánchez-Lite I, Toribio B, Alberca M, Garciá V, Moraleda JM, Sánchez A, Garciá-Sancho J (2017) Intervertebral disc repair by allogeneic mesenchymal bone marrow cells: a randomized controlled trial. Transplantation 101(8):1945–1951. https://doi.org/10.1097/TP.0000000000001484
Ohnishi S, Yanagawa B, Tanaka K, Miyahara Y, Obata H, Kataoka M, Kodama M, Ishibashi-Ueda H, Kangawa K, Kitamura S, Nagaya N (2007) Transplantation of mesenchymal stem cells attenuates myocardial injury and dysfunction in a rat model of acute myocarditis. J Mol Cell Cardiol 42(1):88–97. https://doi.org/10.1016/j.yjmcc.2006.10.003
Panepucci RA, Siufi JLC, Silva WA, Proto-Siquiera R, Neder L, Orellana M, Rocha V, Covas DT, Zago MA (2004) Comparison of gene expression of umbilical cord vein and bone marrow-derived mesenchymal stem cells. Stem Cells 22(7):1263–1278. https://doi.org/10.1634/stemcells.2004-0024
Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284(5411):143–147. https://doi.org/10.1126/science.284.5411.143
Ponte AL, Marais E, Gallay N, Langonné A, Delorme B, Hérault O, Charbord P, Domenech J (2007) The in vitro migration capacity of human bone marrow mesenchymal stem cells: comparison of chemokine and growth factor chemotactic activities. Stem Cells 25(7):1737–1745. https://doi.org/10.1634/stemcells.2007-0054
Prall WC, Saller MM, Scheumaier A, Tucholski T, Taha S, Böcker W, Polzer H (2018) Proliferative and osteogenic differentiation capacity of mesenchymal stromal cells: Influence of harvesting site and donor age. Injury 49:1504–1512. https://doi.org/10.1016/j.injury.2018.06.024
Quevedo HC, Hatzistergos KE, Oskouei BN, Feigenbaum GS, Rodriguez JE, Valdes D, Pattany PM, Zambrano JP, Hu Q, McNiece I, Heldman AW, Hare JM (2009) Allogeneic mesenchymal stem cells restore cardiac function in chronic ischemic cardiomyopathy via trilineage differentiating capacity. Proc Natl Acad Sci 106(33):14022–14027. https://doi.org/10.1073/pnas.0903201106
Ramasamy R, Tong CK, Yip WK, Vellasamy S, Tan BC, Seow HF (2012) Basic fibroblast growth factor modulates cell cycle of human umbilical cord-derived mesenchymal stem cells. Cell Prolif 45(2):132–139. https://doi.org/10.1111/j.1365-2184.2012.00808.x
Renner M, Anliker B, Flory E, Scherer J, Schüßler-Lenz M, Schweizer M, Ivics Z (2016) Regulation for gene and cell therapy medicinal products in Europe. In: Gene therapy and cell therapy through the liver: current aspects and future prospects. Springer, Tokyo. https://doi.org/10.1007/978-4-431-55666-4_10
Ries C, Egea V, Karow M, Kolb H, Jochum M, Neth P (2007) MMP-2, MT1-MMP, and TIMP-2 are essential for the invasive capacity of human mesenchymal stem cells: differential regulation by inflammatory cytokines. Blood 109(9):4055–4063. https://doi.org/10.1182/blood-2006-10-051060
Ringe J, Strassburg S, Neumann K, Endres M, Notter M, Burmester GR, Kaps C, Sittinger M (2007) Towards in situ tissue repair: human mesenchymal stem cells express chemokine receptors CXCR1, CXCR2 and CCR2, and migrate upon stimulation with CXCL8 but not CCL2. J Cell Biochem 101(1):135–146. https://doi.org/10.1002/jcb.21172
Rosenthal N (2003) Prometheus’s vulture and the stem-cell promise. N Engl J Med 349(3):267–274
Rüster B, Göttig S, Ludwig RJ, Bistrian R, Müller S, Seifried E, Gille J, Henschler R (2006) Mesenchymal stem cells display coordinated rolling and adhesion behavior on endothelial cells. Blood 108(12):3938–3944. https://doi.org/10.1182/blood-2006-05-025098
Sato K, Ozaki K, Oh I, Meguro A, Hatanaka K, Nagai T, Muroi K, Ozawa K (2007) Nitric oxide plays a critical role in suppression of T-cell proliferation by mesenchymal stem cells. Blood 109(1):228–234. https://doi.org/10.1182/blood-2006-02-002246
Sen A, Ta M (2020) Altered adhesion and migration of human mesenchymal stromal cells under febrile temperature stress involves NF-κβ pathway. Sci Rep 10:4473. https://doi.org/10.1038/s41598-020-61361-z
Shi Y, Wang Y, Li Q, Liu K, Hou J, Shao C, Wang Y (2018) Immunoregulatory mechanisms of mesenchymal stem and stromal cells in inflammatory diseases. Nat Rev Nephrol 14(8):493–507
Shohara R, Yamamoto A, Takikawa S, Iwase A, Hibi H, Kikkawa F, Ueda M (2012) Mesenchymal stromal cells of human umbilical cord Wharton’s jelly accelerate wound healing by paracrine mechanisms. Cytotherapy 14(10):1171–1181. https://doi.org/10.3109/14653249.2012.706705
Silini A, Parolini O, Huppertz B, Lang I (2013) Soluble factors of amnion-derived cells in treatment of inflammatory and fibrotic pathologies. Curr Stem Cell Res Ther 8(1):6–14. https://doi.org/10.2174/1574888x11308010003
Sobolewski K, Małkowski A, Bańkowski E, Jaworski S (2005) Wharton’s jelly as a reservoir of peptide growth factors. Placenta 26:747–752. https://doi.org/10.1016/j.placenta.2004.10.008
Sohni A, Verfaillie CM (2013) Mesenchymal stem cells migration homing and tracking. Stem Cells Int 2013:130763. https://doi.org/10.1155/2013/130763
Sordi V, Malosio ML, Marchesi F, Mercalli A, Melzi R, Giordano T, Belmonte N, Ferrari G, Leone BE, Bertuzzi F, Zerbini G, Allavena P, Bonifacio E, Piemonti L (2005) Bone marrow mesenchymal stem cells express a restricted set of functionally active chemokine receptors capable of promoting migration to pancreatic islets. Blood 106(2):419–427. https://doi.org/10.1182/blood-2004-09-3507
Spaggiari GM, Capobianco A, Abdelrazik H, Becchetti F, Mingari MC, Moretta L (2008) Mesenchymal stem cells inhibit natural killer-cell proliferation, cytotoxicity, and cytokine production: role of indoleamine 2,3-dioxygenase and prostaglandin E2. Blood 111(3):1327–1333. https://doi.org/10.1182/blood-2007-02-074997
Spees JL, Olson SD, Whitney MJ, Prockop DJ (2006) Mitochondrial transfer between cells can rescue aerobic respiration. Proc Natl Acad Sci U S A 103(5):1283–1288. https://doi.org/10.1073/pnas.0510511103
Stefańska K, Ożegowska K, Hutchings G, Popis M, Moncrieff L, Dompe C, Janowicz K, Pieńkowski W, Gutaj P, Shibli JA, Prado WM, Piotrowska-Kempisty H, Mozdziak P, Bruska M, Zabel M, Kempisty B, Nowicki M (2020) Human Wharton’s jelly—cellular specificity, stemness potency, animal models, and current application in human clinical trials. J Clin Med 9(4):1102. https://doi.org/10.3390/jcm9041102
Steingen C, Brenig F, Baumgartner L, Schmidt J, Schmidt A, Bloch W (2008) Characterization of key mechanisms in transmigration and invasion of mesenchymal stem cells. J Mol Cell Cardiol 44(6):1072–1084. https://doi.org/10.1016/j.yjmcc.2008.03.010
Storms R, Lillich M, Parrott R, Noldner P, Meadows N, Cheatham L, Kurtzberg J (2017) Characterization of MSC derived from umbilical cord tissues. Cytotherapy 19(12):1351–1382. https://doi.org/10.1016/j.jcyt.2017.02.280
Swamynathan P, Venugopal P, Kannan S, Thej C, Kolkundar U, Bhagwat S, Ta M, Sen MA, Balasubramanian S (2014) Are serum-free and xeno-free culture conditions ideal for large scale clinical grade expansion of Wharton’s jelly derived mesenchymal stem cells? A comparative study. Stem Cell Res Ther 5(4):88. https://doi.org/10.1186/scrt477
Szydlak R (2019) Mesenchymal stem cells’ homing and cardiac tissue repair. Acta Biochim Pol 66:483–489. https://doi.org/10.18388/ABP.2019_2890
Szydlak R, Majka M, Lekka M, Kot M, Laidler P (2019) AFM-based analysis of Wharton’s jelly mesenchymal stem cells. Int J Mol Sci 20(18):4351. https://doi.org/10.3390/ijms20184351
Tettelbach W, Cazzell S, Sigal F, Caporusso JM, Agnew PS, Hanft J, Dove C (2019) A multicentre prospective randomised controlled comparative parallel study of dehydrated human umbilical cord (EpiCord) allograft for the treatment of diabetic foot ulcers. Int Wound J 16(1):122–130. https://doi.org/10.1111/iwj.13001
Todeschi MR, El Backly R, Capelli C, Daga A, Patrone E, Introna M, Cancedda R, Mastrogiacomo M (2015) Transplanted umbilical cord mesenchymal stem cells modify the in vivo microenvironment enhancing angiogenesis and leading to bone regeneration. Stem Cells Dev 24:1570–1581. https://doi.org/10.1089/scd.2014.0490
Toma C, Pittenger MF, Cahill KS, Byrne BJ, Kessler PD (2002) Human mesenchymal stem cells differentiate to a cardiomyocyte phenotype in the adult murine heart. Circulation 105(1):93–98. https://doi.org/10.1161/hc0102.101442
Trounson A, McDonald C (2015) Stem cell therapies in clinical trials: progress and challenges. Cell Stem Cell 17(1):11–22
Vagnozzi RJ, Maillet M, Sargent MA, Khalil H, Johansen AK, Schwanekamp JA, York AJ, Huang V, Nahrendorf M, Sadayappan S, Molkentin JD (2019) An acute immune response underlies the benefit of cardiac stem-cell therapy. Nature 577:405–409. https://doi.org/10.1038/s41586-019-1802-2
Vega A, Martín-Ferrero MA, Del Canto F, Alberca M, García V, Munar A, Orozco L, Soler R, Fuertes JJ, Huguet M, Sánchez A, García-Sancho J (2015) Treatment of knee osteoarthritis with allogeneic bone marrow mesenchymal stem cells: a randomized controlled trial. Transplantation 99(8):1681–1690. https://doi.org/10.1097/TP.0000000000000678
Wang Q, Yang Q, Wang Z, Tong H, Ma L, Zhang Y, Shan F, Meng Y, Yuan Z (2016a) Comparative analysis of human mesenchymal stem cells from fetal-bone marrow, adipose tissue, and Warton’s jelly as sources of cell immunomodulatory therapy. Hum Vaccines Immunother 12(1):85–96. https://doi.org/10.1080/21645515.2015.1030549
Wang Y, Li Y, Song L, Li Y, Jiang S, Zhang S (2016b) The transplantation of Akt-overexpressing amniotic fluid-derived mesenchymal stem cells protects the heart against ischemia-reperfusion injury in rabbits. Mol Med Rep 14(1):234–242. https://doi.org/10.3892/mmr.2016.5212
Wang Z, Wang L, Su X, Pu J, Jiang M, He B (2017) Rational transplant timing and dose of mesenchymal stromal cells in patients with acute myocardial infarction: a meta-analysis of randomized controlled trials. Stem Cell Res Ther 8:21. https://doi.org/10.1186/s13287-016-0450-9
Wen Z, Zheng S, Zhou C, Wang J, Wang T (2011) Repair mechanisms of bone marrow mesenchymal stem cells in myocardial infarction. J Cell Mol Med 15(5):1032–1043
Williams AR, Hare JM (2011) Mesenchymal stem cells: biology, pathophysiology, translational findings, and therapeutic implications for cardiac disease. Circ Res 109(8):923–940
Wu KH, Zhou B, Yu CT, Cui B, Lu SH, Han ZC, Liu YL (2007) Therapeutic potential of human umbilical cord derived stem cells in a rat myocardial infarction model. Ann Thorac Surg 83(4):1491–1498. https://doi.org/10.1016/j.athoracsur.2006.10.066
Wu LF, Wang NN, Liu YS, Wei X (2009) Differentiation of Wharton’s jelly primitive stromal cells into insulin-producing cells in comparison with bone marrow mesenchymal stem cells. Tissue Eng Part A 15(10):2865–2873. https://doi.org/10.1089/ten.tea.2008.0579
Yeh YC, Lee WY, Yu CL, Hwang SM, Chung MF, Hsu LW, Chang Y, Lin WW, Tsai MS, Wei HJ, Sung HW (2010) Cardiac repair with injectable cell sheet fragments of human amniotic fluid stem cells in an immune-suppressed rat model. Biomaterials 31(25):6444–6453. https://doi.org/10.1016/j.biomaterials.2010.04.069
Yin C, Liang Y, Zhang J, Ruan G, Li Z, Pang R, Pan X (2016) Umbilical cord-derived mesenchymal stem cells relieve hindlimb ischemia through enhancing angiogenesis in tree shrews. Stem Cells Int 2016:9742034. https://doi.org/10.1155/2016/9742034
Yu H, Lu K, Zhu J, Wang J (2017) Stem cell therapy for ischemic heart diseases. Br Med Bull 21(4):327–342
Zhang W, Liu XC, Yang L, Zhu DL, Zhang YD, Chen Y, Zhang HY (2013) Wharton’s jelly-derived mesenchymal stem cells promote myocardial regeneration and cardiac repair after miniswine acute myocardial infarction. Coron Artery Dis 24(7):549–558. https://doi.org/10.1097/MCA.0b013e3283640f00
Zhang J, Wu Y, Chen A, Zhao Q (2015) Mesenchymal stem cells promote cardiac muscle repair via enhanced neovascularization. Cell Physiol Biochem 35(3):1219–1229. https://doi.org/10.1159/000373945
Zhang C, Zhou G, Cai C, Li J, Chen F, Xie L, Wang W, Zhang Y, Lai X, Ma L (2017) Human umbilical cord mesenchymal stem cells alleviate acute myocarditis by modulating endoplasmic reticulum stress and extracellular signal regulated 1/2-mediated apoptosis. Mol Med Rep 15(6):3515–3520. https://doi.org/10.3892/mmr.2017.6454
Zhang L, Li Y, Guan CY, Tian S, Lv XD, Li JH, Ma X, Xia HF (2018) Therapeutic effect of human umbilical cord-derived mesenchymal stem cells on injured rat endometrium during its chronic phase. Stem Cell Res Ther 9(1):36. https://doi.org/10.1186/s13287-018-0777-5
Zhao Y, Sun X, Cao W, Ma J, Sun L, Qian H, Zhu W, Xu W (2015) Exosomes derived from human umbilical cord mesenchymal stem cells relieve acute myocardial ischemic injury. Stem Cells Int 2015:761643. https://doi.org/10.1155/2015/761643
Zhao L, Liu X, Zhang Y, Liang X, Ding Y, Xu Y, Fang Z, Zhang F (2016a) Enhanced cell survival and paracrine effects of mesenchymal stem cells overexpressing hepatocyte growth factor promote cardioprotection in myocardial infarction. Exp Cell Res 344(1):30–39. https://doi.org/10.1016/j.yexcr.2016.03.024
Zhao Q, Ren H, Han Z (2016b) Mesenchymal stem cells: immunomodulatory capability and clinical potential in immune diseases. J Cell Immunother 2:3–20
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This work was supported by a research grant (STRATEGMED2/265761/10/NCBR/2015) from the National Center for Research and Development in Poland.
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Szydlak, R. (2021). Therapeutic Application of Perinatal Stem Cells in Cardiovascular Diseases: Current Progress and Future Prospects. In: Haider, K.H. (eds) Stem cells: From Potential to Promise. Springer, Singapore. https://doi.org/10.1007/978-981-16-0301-3_8
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