Abstract
It is the time to re-examine with new eyes the findings obtained to date on endothelial progenitor cells (EPCs), in order to eliminate the limitations and to shed light on such findings. This revision might be of help for reordering them and consequently to create a clear puzzle. This last might provide evidence relating to important aspects, including defining, isolating and characterizing EPCs by establishing standardized criteria for EPC research; discriminating between appropriate sub-populations for cell therapy; timing; dosing; priming of cells; and the delivery mode for different applications. Furthermore, influencing factors might also be identified, with the aim of focusing resources and efforts; and the problems associated with local retention and fate of cells in the therapeutic target zone might be resolved. Finally, in order to enable the efficacy of cell therapy at all levels, cell priming, bio-nanotechnology and tissue engineering might be used as emerging tools, and, in particular, their use in combination might be very advantageous.
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Adler AS, Sinha S, Kawahara TL, Zhang JY, Segal E, Chang HY (2007) Motif module map reveals enforcement of aging by continual NF-kappaB activity. Genes Dev 21:3244–3257
Aicher A, Heeschen C, Sasaki K, Urbich C, Zeiher AM, Dimmeler S (2006) Low-energy shock wave for enhancing recruitment of endothelial progenitor cells: a new modality to increase efficacy of cell therapy in chronic hind limb ischemia. Circulation 114:2823–2830
Avgoustiniatos ES, Colton CK (1997) Effect of external oxygen mass transfer resistances on viability of immunoisolated tissue. Ann NY Acad Sci 831:145–167
Banito A, Rashid ST, Acosta JC, Li S, Pereira CF, Geti I, Pinho S, Silva JC, Azuara V, Walsh M, Vallier L, Gil J (2009) Senescence impairs successful reprogramming to pluripotent stem cells. Genes Dev 23(18):2134–2139. doi:10.1101/gad.1811609
Bartunek J, Croissant JD, Wijns W, Gofflot S, de Lavareille A, Vanderheyden M, Kaluzhny Y, Mazouz N, Willemsen P, Penicka M, Mathieu M, Homsy C, De Bruyne B, McEntee K, Lee IW, Heyndrickx GR (2007) Pretreatment of adult bone marrow mesenchymal stem cells with cardiomyogenic growth factors and repair of the chronically infarcted myocardium. Am J Physiol Heart Circ Physiol 292:H1095–H1104
Cerletti M, Jang YC, Finley LW, Haigis MC, Wagers AJ (2012) Short-term calorie restriction enhances skeletal muscle stem cell function. Cell Stem Cell 10:515–519
Chavakis E, Koyanagi M, Dimmeler S (2010) Enhancing the outcome of cell therapy for cardiac repair: progress from bench to bedside and back. Circulation 121:325–335
Davis ME, Motion JP, Narmoneva DA, Takahashi T, Hakuno D, Kamm RD, Zhang S, Lee RT (2005) Injectable self-assembling peptide nanofibers create intramyocardial microenvironments for endothelial cells. Circulation 111:442–450
de Jesus BB, Schneeberger K, Vera E, Tejera A, Harley CB, Blasco MA (2011) The telomerase activator TA-65 elongates short telomeres and increases health span of adult/old mice without increasing cancer incidence. Aging Cell 10:604–621
de Jesus BB, Vera E, Schneeberger K, Tejera AM, Ayuso E, Bosch F, Blasco MA (2012) Telomerase gene therapy in adult and old mice delays aging and increases longevity without increasing cancer. EMBO Mol Med 4(8):691–704. doi:10.1002/emmm.201200245
Ghanem A, Steingen C, Brenig F, Funcke F, Bai ZY, Hall C, Chin CT, Nickenig G, Bloch W, Tiemann K (2009) Focused ultrasound-induced stimulation of microbubbles augments site-targeted engraftment of mesenchymal stem cells after acute myocardial infarction. J Mol Cell Cardiol 47:411–418
Giannotti G, Doerries C, Mocharla PS, Mueller MF, Bahlmann FH, Horvath T, Jiang H, Sorrentino SA, Steenken N, Manes C, Marzilli M, Rudolph KL, Luscher TF, Drexler H, Landmesser U (2010) Impaired endothelial repair capacity of early endothelial progenitor cells in prehypertension: relation to endothelial dysfunction. Hypertension 55:1389–1397
Hahn JY, Cho HJ, Kang HJ, Kim TS, Kim MH, Chung JH, Bae JW, Oh BH, Park YB, Kim HS (2008) Pre-treatment of mesenchymal stem cells with a combination of growth factors enhances gap junction formation, cytoprotective effect on cardiomyocytes, and therapeutic efficacy for myocardial infarction. J Am Coll Cardiol 51:933–943
Jaskelioff M, Muller FL, Paik JH, Thomas E, Jiang S, Adams AC, Sahin E, Kost-Alimova M, Protopopov A, Cadiñanos J, Horner JW, Maratos-Flier E, Depinho RA (2011) Telomerase reactivation reverses tissue degeneration in aged telomerase-deficient mice. Nature 469(7328):102–106. doi:10.1038/nature09603
Laflamme MA, Murry CE (2005) Regenerating the heart. Nat Biotechnol 23:845–856
Lapasset L, Milhavet O, Prieur A, Besnard E, Babled A, Aït-Hamou N, Leschik J, Pellestor F, Ramirez JM, De Vos J, Lehmann S, Lemaitre JM (2011) Rejuvenating senescent and centenarian human cells by reprogramming through the pluripotent state. Genes Dev 25(21):2248–2253. doi:10.1101/gad.173922.111
Melero-Martin JM, De Obaldia ME, Kang SY, Khan ZA, Yuan L, Oettgen P, Bischoff J (2008) Engineering robust and functional vascular networks in vivo with human adult and cord blood-derived progenitor cells. Circ Res 103:194–202
Mias C, Trouche E, Seguelas MH, Calcagno F, Dignat-George F, Sabatier F, Piercecchi-Marti MD, Daniel L, Bianchi P, Calise D, Bourin P, Parini A, Cussac D (2008) Ex vivo pretreatment with melatonin improves survival, proangiogenic/mitogenic activity, and efficiency of mesenchymal stem cells injected into ischemic kidney. Stem Cells 26:1749–1757
Mooney DJ, Vandenburgh H (2008) Cell delivery mechanisms for tissue repair. Cell Stem Cell 2:205–213
Padin-Iruegas ME, Misao Y, Davis ME, Segers VF, Esposito G, Tokunou T, Urbanek K, Hosoda T, Rota M, Anversa P, Leri A, Lee RT, Kajstura J (2009) Cardiac progenitor cells and biotinylated insulin-like growth factor-1 nanofibers improve endogenous and exogenous myocardial regeneration after infarction. Circulation 120:876–887
Penn MS, Mangi AA (2008) Genetic enhancement of stem cell engraftment, survival, and efficacy. Circ Res 102:1471–1482
Rando TA, Chang HY (2012) Aging, rejuvenation, and epigenetic reprogramming: resetting the aging clock. Cell 148:46–57
Segers VF, Tokunou T, Higgins LJ, MacGillivray C, Gannon J, Lee RT (2007) Local delivery of protease-resistant stromal cell derived factor-1 for stem cell recruitment after myocardial infarction. Circulation 116:1683–1692
Selman C, Tullet JM, Wieser D, Irvine E, Lingard SJ, Choudhury AI, Claret M, Al-Qassab H, Carmignac D, Ramadani F, Woods A, Robinson IC, Schuster E, Batterham RL, Kozma SC, Thomas G, Carling D, Okkenhaug K, Thornton JM, Partridge L, Gems D, Withers DJ (2009) Ribosomal protein S6 kinase 1 signaling regulates mammalian life span. Science 326(5949):140–144. doi:10.1126/science.1177221
Sorrentino SA, Bahlmann FH, Besler C, Muller M, Schulz S, Kirchhoff N, Doerries C, Horvath T, Limbourg A, Limbourg F, Fliser D, Haller H, Drexler H, Landmesser U (2007) Oxidant stress impairs in vivo re-endothelialisation capacity of endothelial progenitor cells from patients with type 2 diabetes mellitus: restoration by the peroxisome proliferator-activated receptor-gamma agonist rosiglitazone. Circulation 116:163–173
Taljaard M, Ward MR, Kutryk MJ, Courtman DW, Camack NJ, Goodman SG, Parker TG, Dick AJ, Galipeau J, Stewart DJ (2010) Rationale and design of enhanced angiogenic cell therapy in acute myocardial infarction (ENACT-AMI): the first randomized placebo-controlled trial of enhanced progenitor cell therapy for acute myocardial infarction. Am Heart J 159:354–360
Terrovitis J, Lautamaki R, Bonios M, Fox J, Engles JM, Yu J, Leppo MK, Pomper MG, Wahl RL, Seidel J, Tsui BM, Bengel FM, Abraham MR, Marban E (2009) Noninvasive quantification and optimization of acute cell retention by in vivo positron emission tomography after intramyocardial cardiac-derived stem cell delivery. J Am Coll Cardiol 54:1619–1626
Tongers J, Webber MJ, Losordo DW (2009a) Bioengineering to enhance progenitor cell therapeutics. Tex Heart Inst J 36:140–144
Tongers J, Webber MG, Renault M-A, Roncalli JG, Jujo K, Wu X, Klyachko E, Thorne T, Stupp SI, Losordo DW (2009b) Abstract 4931: RGDS-epitope presenting peptide amphiphile nanofibers enhance therapeutic potency of cell-based strategies in ischemic tissue. Circulation 120:S1023-c-1024
Zen K, Okigaki M, Hosokawa Y, Adachi Y, Nozawa Y, Takamiya M, Tatsumi T, Urao N, Tateishi K, Takahashi T, Matsubara H (2006) Myocardium-targeted delivery of endothelial progenitor cells by ultrasound-mediated microbubble destruction improves cardiac function via an angiogenic response. J Mol Cell Cardiol 40:799–809
Zimmermann WH, Melnychenko I, Wasmeier G, Didié M, Naito H, Nixdorff U, Hess A, Budinsky L, Brune K, Michaelis B, Dhein S, Schwoerer A, Ehmke H, Eschenhagen T (2006) Engineered heart tissue grafts improve systolic and diastolic function in infarcted rat hearts. Nat Med 12:452–458
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Balistreri, C.R. (2017). Endothelial Progenitor Cells: A Real Hope or an Unrealizable Dream? Which Measures or Strategies Are Necessary for making EPCs a clinical reality? Focus on a Potential Roadmap. In: Endothelial Progenitor Cells. UNIPA Springer Series. Springer, Cham. https://doi.org/10.1007/978-3-319-55107-4_3
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