Pluripotency of human embryonic and induced pluripotent stem cells for cardiac and vascular regeneration

 

PDF Download Buy Article Permissions and Reprints

Summary

Cardiac and vascular abnormalities and disease syndromes are major causes of death both during human development and with aging. To identify the cause of congenital defects and to combat this epidemic in the aging population, new models must be created for scientific investigation and new therapies must be developed. Recent advances in pluripotent stem cell biology offer renewed hope for tackling these problems. Of particular importance has been the creation of induced pluripotent (iPS) cells from adult tissues and organs through the forced expression of two to four transcription factors. Moreover, iPS cells, which are phenotypically indistinguishable from embryonic stem (ES) cells, can be generated from any patient. This unique capacity when coupled with samples from patients who have congenital and genetic defects of unknown aetiology should permit the creation of new model systems that foment scientific investigation. Moreover, creation of patient-specific cells should overcome many of the immunological limitations that currently impede therapeutic applications associated with other pluripotent stem cells and their derivatives. The aims of this paper will be to discuss cardiac and vascular diseases and show how iPS cells may be employed to overcome some of the most significant scientific and clinical hurdles facing this field.

• References

• 1 Pierpont ME, Basson CT, Benson DW. et al Genetic basis for congenital heart defects: Current knowledge – A scientific statement from the American heart association congenital cardiac defects committee, council on cardiovascular disease in the young. Circulation 2007; 115: 3015-3038.
  CrossrefPubMedGoogle Scholar
• 2 Najjar SS, Scuteri A, Lakatta EG. Arterial aging – Is it an immutable cardiovascular risk factor?. Hypertension 2005; 46: 454-462.
  CrossrefPubMedGoogle Scholar
• 3 Lakatta EG, Wang MY, Najjar SS. Arterial aging and subclinical arterial disease are fundamentally intertwined at macroscopic and molecular levels. Med Clin North Am 2009; 93: 583-604.
  CrossrefPubMedGoogle Scholar
• 4 Chantler PD, Lakatta EG, Najjar SS. Arterial-ventricular coupling: mechanistic insights into cardiovascular performance at rest and during exercise. J Appl Physiol 2008; 105: 1342-1351.
  CrossrefPubMedGoogle Scholar
• 5 Steffens S, Montecucco F, Mach F. The inflammatory response as a target to reduce myocardial ischaemia and reperfusion injury. Thromb Haemost 2009; 102: 240-247.
  Article in Thieme ConnectPubMedGoogle Scholar
• 6 Vanhoutte PM, Shimokawa H, Tang EHC. et al Endothelial dysfunction and vascular disease. Acta Physiol 2009; 196: 193-222.
  CrossrefPubMedGoogle Scholar
• 7 Vanhoutte PM. Endothelial dysfunction – The first step toward coronary arteriosclerosis. Circ J 2009; 73: 595-601.
  CrossrefPubMedGoogle Scholar
• 8 Wobus AM, Boheler KR. Embryonic stem cells: prospects for developmental biology and cell therapy. Physiol Rev 2005; 85: 635-678.
  CrossrefPubMedGoogle Scholar
• 9 Yamanaka S, Li JL, Kania G. et al Pluripotency of embryonic stem cells. Cell Tissue Res 2008; 331: 5-22.
  CrossrefPubMedGoogle Scholar
• 10 Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006; 126: 663-676.
  CrossrefPubMedGoogle Scholar
• 11 Okita K, Ichisaka T, Yamanaka S. Generation of germline-competent induced pluripotent stem cells. Nature 2007; 448: 313-317.
  CrossrefPubMedGoogle Scholar
• 12 Zou JZ, Maeder ML, Mali P. et al Gene targeting of a disease-related gene in human induced pluripotent stem and embryonic stem cells. Cell Stem Cell 2009; 05: 97-110.
  CrossrefPubMedGoogle Scholar
• 13 Meissner A, Wernig M, Jaenisch R. Direct reprogramming of genetically unmodified fibroblasts into pluripotent stem cells. Nat Biotechnol 2007; 25: 1177-1181.
  CrossrefPubMedGoogle Scholar
• 14 Boheler KR. Stem cell pluripotency: A cellular trait that depends on transcription factors, chromatin state and a checkpoint deficient cell cycle. J Cell Physiol 2009; 221: 10-17.
  CrossrefPubMedGoogle Scholar
• 15 Perino MG, Yamanaka S, Li JL. et al Cardiomyogenic stem and progenitor cell plasticity and the dissection of cardiopoiesis. JMolCellCardiol 2008; 45: 475-494.
  PubMedGoogle Scholar
• 16 Yamanaka S. A Fresh Look at iPS Cells. Cell 2009; 137: 13-17.
  CrossrefPubMedGoogle Scholar
• 17 Takahashi K, Tanabe K, Ohnuki M. et al Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 2007; 131: 861-872.
  CrossrefPubMedGoogle Scholar
• 18 Huangfu DW, Osafune K, Maehr R. et al Induction of pluripotent stem cells from primary human fibroblasts with only Oct4 and Sox2. Nat Biotechnol 2008; 26: 1269-1275.
  CrossrefPubMedGoogle Scholar
• 19 Yu J, Vodyanik MA, Smuga-Otto K. et al Induced pluripotent stem cell lines derived from human somatic cells. Science 2007; 318: 1917-1920.
  CrossrefPubMedGoogle Scholar
• 20 Stadtfeld M, Hochedlinger K. Without a trace? PiggyBacing toward pluripotency. Nat Methods 2009; 06: 329-330.
  CrossrefPubMedGoogle Scholar
• 21 Stadtfeld M, Nagaya M, Utikal J, Weir G, Hochedlinger K. Induced Pluripotent Stem Cells Generated Without Viral Integration. Science 2008; 322: 945-949.
  CrossrefPubMedGoogle Scholar
• 22 Brambrink T, Foreman R, Welstead GG, Lengner CJ, Wernig M, Suh H, Jaenisch R. Sequential expression of pluripotency markers during direct reprogramming of mouse somatic cells. Cell Stem Cell 2008; 02: 151-159.
  CrossrefPubMedGoogle Scholar
• 23 Stadtfeld M, Maherali N, Breault DT. et al Defining molecular cornerstones during fibroblast to iPS cell reprogramming in mouse. Cell Stem Cell 2008; 02: 230-240.
  CrossrefPubMedGoogle Scholar
• 24 Maherali N, Sridharan R, Xie W. et al Directly reprogrammed fibroblasts show global epigenetic remodeling and widespread tissue contribution. Cell Stem Cell 2007; 01: 55-70.
  CrossrefPubMedGoogle Scholar
• 25 Wernig M, Meissner A, Foreman R. et al In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state. Nature 2007; 448: 318-324.
  CrossrefPubMedGoogle Scholar
• 26 Chin MH, Mason MJ, Xie W. et al Induced pluripotent stem cells and embryonic stem cells are distinguished by gene expression signatures. Cell Stem Cell 2009; 05: 111-123.
  CrossrefPubMedGoogle Scholar
• 27 Nakagawa M, Koyanagi M, Tanabe K. et al Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nat Biotechnol 2008; 26: 101-106.
  CrossrefPubMedGoogle Scholar
• 28 Aoi T, Yae K, Nakagawa M. et al Generation of pluripotent stem cells from adult mouse liver and stomach cells. Science 2008; 321: 699-702.
  CrossrefPubMedGoogle Scholar
• 29 Stadtfeld M, Brennand K, Hochedlinger K. Reprogramming of pancreatic beta cells into induced pluripotent stem cells. Current Biol 2008; 18: 890-894.
  CrossrefPubMedGoogle Scholar
• 30 Kim JB, Zaehres H, Wu GM. et al Pluripotent stem cells induced from adult neural stem cells by reprogramming with two factors. Nature 2008; 454: 646-650.
  CrossrefPubMedGoogle Scholar
• 31 Eminli S, Utikal J, Arnold K. et al Reprogramming of neural progenitor cells into induced pluripotent stem cells in the absence of exogenous Sox2 expression. Stem Cells 2008; 26: 2467-2474.
  CrossrefPubMedGoogle Scholar
• 32 Hanna J, Markoulaki S, Schorderet P. et al Direct reprogramming of terminally differentiated mature B lymphocytes to pluripotency. Cell 2008; 133: 250-264.
  CrossrefPubMedGoogle Scholar
• 33 Aasen T, Raya A, Barrero MJ. et al Efficient and rapid generation of induced pluripotent stem cells from human keratinocytes. Nat Biotechnol 2008; 26: 1276-1284.
  CrossrefPubMedGoogle Scholar
• 34 Maherali N, Ahfeldt T, Rigamonti A. et al A high-efficiency system for the generation and study of human induced pluripotent stem cells. Cell Stem Cell 2008; 03: 340-345.
  CrossrefPubMedGoogle Scholar
• 35 Maherali N, Hochedlinger K. Guidelines and techniques for the generation of induced pluripotent stem cells. Cell Stem Cell 2008; 03: 595-605.
  CrossrefPubMedGoogle Scholar
• 36 Gundry RL, Boheler KR, Van Eyk JE. et al A novel role for proteomics in the discovery of cell-surface markers on stem cells: Scratching the surface. Proteom Clin Appl 2008; 02: 892-903.
  CrossrefPubMedGoogle Scholar
• 37 Kim JH, Auerbach JM, Rodriguez-Gomez JA. et al Dopamine neurons derived from embryonic stem cells function in an animal model of Parkinson's disease. Nature 2002; 418: 50-56.
  CrossrefPubMedGoogle Scholar
• 38 Blyszczuk P, Czyz J, Kania G. et al Expression of Pax4 in embryonic stem cells promotes differentiation of nestin-positive progenitor and insulin-producing cells. Proc Natl Acad Sci USA 2003; 100: 998-1003.
  CrossrefPubMedGoogle Scholar
• 39 Choi K, Kennedy M, Kazarov A. et al A common precursor for hematopoietic and endothelial cells. Development 1998; 125: 725-732.
  PubMedGoogle Scholar
• 40 Fehling HJ, Lacaud G, Kubo A. et al Tracking mesoderm induction and its specification to the hemangioblast during embryonic stem cell differentiation. Development 2003; 130: 4217-4227.
  CrossrefPubMedGoogle Scholar
• 41 Huber TL, Kouskoff V, Fehling HJ. et al Haemangioblast commitment is initiated in the primitive streak of the mouse embryo. Nature 2004; 432: 625-630.
  CrossrefPubMedGoogle Scholar
• 42 Murry CE, Keller G. Differentiation of embryonic stem cells to clinically relevant populations: Lessons from embryonic development. Cell 2008; 132: 661-680.
  CrossrefPubMedGoogle Scholar
• 43 Shalaby F, Ho J, Stanford WL. et al A requirement for Flk1 in primitive and definitive hematopoiesis and vasculogenesis. Cell 1997; 89: 981-990.
  CrossrefPubMedGoogle Scholar
• 44 Kouskoff V, Lacaud G, Schwantz S. et al Sequential development of hematopoietic and cardiac mesoderm during embryonic stem cell differentiation. Proc Natl Acad Sci USA 2005; 102: 13170-13175.
  CrossrefPubMedGoogle Scholar
• 45 Kennedy M, D'Souza SL, Lynch-Kattman M. et al Development of the hemangioblast defines the onset of hematopoiesis in human ES cell differentiation cultures. Blood 2007; 109: 2679-2687.
  PubMedGoogle Scholar
• 46 Kofidis T, de Bruin JL, Hoyt G. et al Myocardial restoration with embryonic stem cell bioartificial tissue transplantation. J Heart Lung Transpl 2005; 24: 737-744.
  CrossrefPubMedGoogle Scholar
• 47 Swijnenburg RJ, Tanaka M, Vogel H. et al Embryonic stem cell immunogenicity increases upon differentiation after transplantation into ischemic myocardium. Circulation 2005; 112: I166-I172.
  PubMedGoogle Scholar
• 48 Kolossov E, Bostani T, Roell W. et al Engraftment of engineered ES cell-derived cardiomyocytes but not BM cells restores contractile function to the infarcted myocardium. J Exp Med 2006; 203: 2315-2327.
  CrossrefPubMedGoogle Scholar
• 49 Laflamme MA, Chen KY, Naumova AV. et al Cardiomyocytes derived from human embryonic stem cells in pro-survival factors enhance function of infarcted rat hearts. Nat Biotechnol 2007; 25: 1015-1024.
  CrossrefPubMedGoogle Scholar
• 50 Li Z, Wu JC, Sheikh AY. et al Differentiation, survival, and function of embryonic stem cell-derived endothelial cells for ischemic heart disease. Circulation 2007; 116: I46-I54.
  PubMedGoogle Scholar
• 51 Wang ZZ, Au P, Chen T. et al Endothelial cells derived from human embryonic stem cells form durable blood vessels in vivo. Nat Biotechnol 2007; 25: 317-318.
  CrossrefPubMedGoogle Scholar
• 52 Hanna J, Wernig M, Markoulaki S. et al Treatment of sickle cell anemia mouse model with iPS cells generated from autologous skin. Science 2007; 318: 1920-1923.
  CrossrefPubMedGoogle Scholar
• 53 Wernig M, Zhao JP, Pruszak J. et al Neurons derived from reprogrammed fibroblasts functionally integrate into the fetal brain and improve symptoms of rats with Parkinson's disease. Proc Natl Acad Sci USA 2008; 105: 5856-5861.
  CrossrefPubMedGoogle Scholar
• 54 Nelson TJ, Martinez-Fernandez A, Yamada S. et al Repair of Acute Myocardial Infarction by Human Stemness Factors Induced Pluripotent Stem Cells. Circulation 2009; 120: 408-416.
  CrossrefPubMedGoogle Scholar
• 55 Narazaki G, Uosaki H, Teranishi M. et al Directed and systematic differentiation of cardiovascular cells from mouse induced pluripotent stem cells. Circulation 2008; 118: 498-506.
  CrossrefPubMedGoogle Scholar
• 56 Zhang JH, Wilson GF, Soerens AG. et al Functional cardiomyocytes derived from human induced pluripotent stem cells. CircRes 2009; 104: E30-E41.
  PubMedGoogle Scholar
• 57 Tateishi K, He J, Taranova O. et al Generation of Insulin-secreting Islet-like Clusters from Human Skin Fibroblasts. J Biol Chem 2008; 283: 31601-31607.
  CrossrefPubMedGoogle Scholar
• 58 Xu D, Alipio Z, Fink LM. et al Phenotypic correction of murine hemophilia A using an iPS cell-based therapy. Proc Natl Acad Sci USA 2009; 106: 808-813.
  CrossrefPubMedGoogle Scholar
• 59 Dimos JT, Rodolfa KT, Niakan KK. et al Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons. Science 2008; 321: 1218-1221.
  CrossrefPubMedGoogle Scholar
• 60 Park IH, Arora N, Huo H. et al Disease-specific induced pluripotent stem cells. Cell 2008; 134: 877-886.
  CrossrefPubMedGoogle Scholar
• 61 Menasche P. Stem cells for clinical use in cardiovascular medicine – Current limitations and future perspectives. Thromb Haemost 2005; 94: 697-701.
  Article in Thieme ConnectPubMedGoogle Scholar
• 62 Fraidenraich D, Stillwell E, Romero E. et al Rescue of cardiac defects in Id knock-out embryos by injection of embryonic stem cells. Science 2004; 306: 247-252.
  CrossrefPubMedGoogle Scholar