Skip to main content

Therapeutic Application of Adult Stem Cells in the Heart

  • Protocol
  • First Online:
Adult Stem Cells

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1553))

Abstract

Cell therapies have been explored as a potential treatment avenue to treat heart diseases, such as myocardial infarction, doxorubicin-induced cardiomyopathy, and heart failure. Embryonic and adult stem cells (ASCs) have been examined in animal and clinical settings. Unlike embryonic and induced pluripotent stem cells, ASCs do not pose a threat to form teratomas, nor do they have immune system concerns, making them ideal for therapeutic use in humans. In this review, we will investigate different characteristics and sources of adult stem cells and progenitor cells, as well as determine their efficacy in cell transplantation in experimental and clinical trials. In addition, we will propose other research avenues that may promote further understanding and use of ASCs in therapeutic designs.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 99.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 129.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, Das SR, FS d, JP D, HJ F, VJ H, MD H, CR I, MC J, SE J, BM K, JH L, LD L, Liu S, RH M, DJ M, DK MG, ER M III, CS M, Muntner P, ME M, Nasir K, RW N, Nichol G, Palaniappan L, DK P, MJ R, CJ R, Rosamond W, PD S, Stein J, Towfighi A, TN T, SS V, Woo D, RW Y, MB T (2016) Heart disease and stroke statistics-2016 update: a report from the american heart association. Circulation 133:e38–e360. doi:10.1161/CIR.0000000000000350 CIR.0000000000000350 [pii]

    Article  PubMed  Google Scholar 

  2. Sheydina A, Riordon DR, Boheler KR (2011) Molecular mechanisms of cardiomyocyte aging. Clin Sci (Lond) 121:315–329. doi:10.1042/CS20110115 CS20110115 [pii]

    Article  CAS  Google Scholar 

  3. Cieslik KA, Taffet GE, Crawford JR, Trial J, Mejia OP, Entman ML (2013) AICAR-dependent AMPK activation improves scar formation in the aged heart in a murine model of reperfused myocardial infarction. J Mol Cell Cardiol 63:26–36. doi:10.1016/j.yjmcc.2013.07.005 S0022-2828(13)00227-7 [pii]

    Article  CAS  PubMed  Google Scholar 

  4. Aronow WS (2006) Heart disease and aging. Med Clin North Am 90:849–862. doi:10.1016/j.mcna.2006.05.009 S0025-7125(06)00047-2 [pii]

    Article  PubMed  Google Scholar 

  5. Beltrami AP, Urbanek K, Kajstura J, Yan SM, Finato N, Bussani R, Nadal-Ginard B, Silvestri F, Leri A, Beltrami CA, Anversa P (2001) Evidence that human cardiac myocytes divide after myocardial infarction. N Engl J Med 344:1750–1757. doi:10.1056/NEJM200106073442303

    Article  CAS  PubMed  Google Scholar 

  6. Bergmann O, Bhardwaj RD, Bernard S, Zdunek S, Barnabe-Heider F, Walsh S, Zupicich J, Alkass K, Buchholz BA, Druid H, Jovinge S, Frisen J (2009) Evidence for cardiomyocyte renewal in humans. Science 324:98–102. doi:10.1126/science.1164680 324/5923/98 [pii]

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Ali SR, Hippenmeyer S, Saadat LV, Luo L, Weissman IL, Ardehali R (2014) Existing cardiomyocytes generate cardiomyocytes at a low rate after birth in mice. Proc Natl Acad Sci U S A 111:8850–8855. doi:10.1073/pnas.1408233111 1408233111 [pii]

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM (1998) Embryonic stem cell lines derived from human blastocysts. Science 282:1145–1147

    Article  CAS  PubMed  Google Scholar 

  9. Baker DE, Harrison NJ, Maltby E, Smith K, Moore HD, Shaw PJ, Heath PR, Holden H, Andrews PW (2007) Adaptation to culture of human embryonic stem cells and oncogenesis in vivo. Nat Biotechnol 25:207–215. doi:10.1038/nbt1285 nbt1285 [pii]

    Article  CAS  PubMed  Google Scholar 

  10. Singla DK (2009) Embryonic stem cells in cardiac repair and regeneration. Antioxid Redox Signal 11:1857–1863. doi:10.1089/ars.2009.2491 10.1089/ARS.2009.2491 [pii]

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Singla DK, Ahmed A, Singla R, Yan B (2012) Embryonic stem cells improve cardiac function in Doxorubicin-induced cardiomyopathy mediated through multiple mechanisms. Cell Transplant 21:1919–1930. doi:10.3727/096368911X627552 ct0556singla [pii]

    Article  PubMed  PubMed Central  Google Scholar 

  12. Glass C, Singla DK (2012) Overexpression of TIMP-1 in embryonic stem cells attenuates adverse cardiac remodeling following myocardial infarction. Cell Transplant 21:1931–1944. doi:10.3727/096368911X627561 ct2381glass [pii]

    Article  PubMed  Google Scholar 

  13. Yan B, Singla RD, Abdelli LS, Singal PK, Singla DK (2013) Regulation of PTEN/Akt pathway enhances cardiomyogenesis and attenuates adverse left ventricular remodeling following thymosin beta4 Overexpressing embryonic stem cell transplantation in the infarcted heart. PLoS One 8:e75580. doi:10.1371/journal.pone.0075580 PONE-D-13-29439 [pii]

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, Nie J, Jonsdottir GA, Ruotti V, Stewart R, Slukvin II, Thomson JA (2007) Induced pluripotent stem cell lines derived from human somatic cells. Science 318:1917–1920. doi:10.1126/science.1151526 1151526 [pii]

    Article  CAS  PubMed  Google Scholar 

  15. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131:861–872. doi:10.1016/j.cell.2007.11.019 S0092-8674(07)01471-7 [pii]

    Article  CAS  PubMed  Google Scholar 

  16. Ben-David U, Benvenisty N (2011) The tumorigenicity of human embryonic and induced pluripotent stem cells. Nat Rev Cancer 11:268–277. doi:10.1038/nrc3034 nrc3034 [pii]

    Article  CAS  PubMed  Google Scholar 

  17. Singla DK, Long X, Glass C, Singla RD, Yan B (2011) Induced pluripotent stem (iPS) cells repair and regenerate infarcted myocardium. Mol Pharm 8:1573–1581. doi:10.1021/mp2001704

    Article  CAS  PubMed  Google Scholar 

  18. Yan B, Singla DK (2013) Transplanted induced pluripotent stem cells mitigate oxidative stress and improve cardiac function through the Akt cell survival pathway in diabetic cardiomyopathy. Mol Pharm 10:3425–3432. doi:10.1021/mp400258d

    Article  CAS  PubMed  Google Scholar 

  19. Merino H, Singla DK (2014) Notch-1 mediated cardiac protection following embryonic and induced pluripotent stem cell transplantation in doxorubicin-induced heart failure. PLoS One 9:e101024. doi:10.1371/journal.pone.0101024 PONE-D-14-15179 [pii]

    Article  PubMed  PubMed Central  Google Scholar 

  20. Jopling C, Boue S, Izpisua Belmonte JC (2011) Dedifferentiation, transdifferentiation and reprogramming: three routes to regeneration. Nat Rev Mol Cell Biol 12:79–89. doi:10.1038/nrm3043 nrm3043 [pii]

    Article  CAS  PubMed  Google Scholar 

  21. Lin R, Iacovitti L (2015) Classic and novel stem cell niches in brain homeostasis and repair. Brain Res 1628:327–342. doi:10.1016/j.brainres.2015.04.029 S0006-8993(15)00325-X [pii]

    Article  CAS  PubMed  Google Scholar 

  22. Calvi LM, Link DC (2014) Cellular complexity of the bone marrow hematopoietic stem cell niche. Calcif Tissue Int 94:112–124. doi:10.1007/s00223-013-9805-8

    Article  CAS  PubMed  Google Scholar 

  23. Ambler CA, Maatta A (2009) Epidermal stem cells: location, potential and contribution to cancer. J Pathol 217:206–216. doi:10.1002/path.2468

    Article  CAS  PubMed  Google Scholar 

  24. Gimble JM, Grayson W, Guilak F, Lopez MJ, Vunjak-Novakovic G (2011) Adipose tissue as a stem cell source for musculoskeletal regeneration. Front Biosci (Schol Ed) 3:69–81 133 [pii]

    Article  Google Scholar 

  25. Gopinath SD, Rando TA (2008) Stem cell review series: aging of the skeletal muscle stem cell niche. Aging Cell 7:590–598. doi:10.1111/j.1474-9726.2008.00399.x ACE399 [pii]

    Article  CAS  PubMed  Google Scholar 

  26. Habeeb MA, Vishwakarma SK, Bardia A, Khan AA (2015) Hepatic stem cells: a viable approach for the treatment of liver cirrhosis. World J Stem Cells 7:859–865. doi:10.4252/wjsc.v7.i5.859

    Article  PubMed  PubMed Central  Google Scholar 

  27. Leatherman J (2013) Stem cells supporting other stem cells. Front Genet 4:257. doi:10.3389/fgene.2013.00257

    Article  PubMed  PubMed Central  Google Scholar 

  28. Kaukua N, Shahidi MK, Konstantinidou C, Dyachuk V, Kaucka M, Furlan A, An Z, Wang L, Hultman I, Ahrlund-Richter L, Blom H, Brismar H, Lopes NA, Pachnis V, Suter U, Clevers H, Thesleff I, Sharpe P, Ernfors P, Fried K, Adameyko I (2014) Glial origin of mesenchymal stem cells in a tooth model system. Nature 513:551–554. doi:10.1038/nature13536 nature13536 [pii]

    Article  CAS  PubMed  Google Scholar 

  29. Mills JC, Shivdasani RA (2011) Gastric epithelial stem cells. Gastroenterology 140:412–424. doi:10.1053/j.gastro.2010.12.001 S0016-5085(10)01746-4 [pii]

    Article  CAS  PubMed  Google Scholar 

  30. Imhof BA, Aurrand-Lions M (2004) Adhesion mechanisms regulating the migration of monocytes. Nat Rev Immunol 4:432–444. doi:10.1038/nri1375 nri1375 [pii]

    Article  CAS  PubMed  Google Scholar 

  31. Reya T, Morrison SJ, Clarke MF, Weissman IL (2001) Stem cells, cancer, and cancer stem cells. Nature 414:105–111. doi:10.1038/35102167 35102167 [pii]

    Article  CAS  PubMed  Google Scholar 

  32. Xu S, Zhu J, Yu L, Fu G (2012) Endothelial progenitor cells: current development of their paracrine factors in cardiovascular therapy. J Cardiovasc Pharmacol 59:387–396. doi:10.1097/FJC.0b013e3182440338

    Article  CAS  PubMed  Google Scholar 

  33. Chong JJ, Forte E, Harvey RP (2014) Developmental origins and lineage descendants of endogenous adult cardiac progenitor cells. Stem Cell Res 13:592–614. doi:10.1016/j.scr.2014.09.008 S1873-5061(14)00110-X [pii]

    Article  CAS  PubMed  Google Scholar 

  34. Iancu CB, Iancu D, RenTea I, Hostiuc S, Dermengiu D, Rusu MC (2015) Molecular signatures of cardiac stem cells. Rom J Morphol Embryol 56:1255–1262 56041512551262 [pii]

    PubMed  Google Scholar 

  35. Ye J, Yeghiazarians Y (2014) Cardiac stem cell therapy: review of the native cardiac progenitor cells and future direction. J Cardiovasc Pharmacol 63:85–94. doi:10.1097/FJC.0b013e318299ebc0

    Article  CAS  PubMed  Google Scholar 

  36. Klimczak A, Kozlowska U (2016) Mesenchymal stromal cells and tissue-specific progenitor cells: their role in tissue homeostasis. Stem Cells Int 2016:4285215. doi:10.1155/2016/4285215

    Article  PubMed  Google Scholar 

  37. Pearson J, Lopez-Onieva L, Rojas-Rios P, Gonzalez-Reyes A (2009) Recent advances in Drosophila stem cell biology. Int J Dev Biol 53:1329–1339. doi:10.1387/ijdb.072431jp 072431jp [pii]

    Article  CAS  PubMed  Google Scholar 

  38. Joshi PM, Riddle MR, Djabrayan NJ, Rothman JH (2010) Caenorhabditis elegans as a model for stem cell biology. Dev Dyn 239:1539–1554. doi:10.1002/dvdy.22296

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Poss KD, Wilson LG, Keating MT (2002) Heart regeneration in zebrafish. Science 298:2188–2190. doi:10.1126/science.1077857 298/5601/2188 [pii]

    Article  CAS  PubMed  Google Scholar 

  40. Jopling C, Sleep E, Raya M, Marti M, Raya A, Izpisua Belmonte JC (2010) Zebrafish heart regeneration occurs by cardiomyocyte dedifferentiation and proliferation. Nature 464:606–609. doi:10.1038/nature08899 nature08899 [pii]

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. van der Bogt KE, Sheikh AY, Schrepfer S, Hoyt G, Cao F, Ransohoff KJ, Swijnenburg RJ, Pearl J, Lee A, Fischbein M, Contag CH, Robbins RC, Wu JC (2008) Comparison of different adult stem cell types for treatment of myocardial ischemia. Circulation 118:S121–S129. doi:10.1161/CIRCULATIONAHA.107.759480 118/14_suppl_1/S121 [pii]

    Article  PubMed  PubMed Central  Google Scholar 

  42. Tamaki T, Akatsuka A, Okada Y, Uchiyama Y, Tono K, Wada M, Hoshi A, Iwaguro H, Iwasaki H, Oyamada A, Asahara T (2008) Cardiomyocyte formation by skeletal muscle-derived multi-myogenic stem cells after transplantation into infarcted myocardium. PLoS One 3:e1789. doi:10.1371/journal.pone.0001789

    Article  PubMed  PubMed Central  Google Scholar 

  43. Tang XL, Rokosh G, Sanganalmath SK, Yuan F, Sato H, Mu J, Dai S, Li C, Chen N, Peng Y, Dawn B, Hunt G, Leri A, Kajstura J, Tiwari S, Shirk G, Anversa P, Bolli R (2010) Intracoronary administration of cardiac progenitor cells alleviates left ventricular dysfunction in rats with a 30-day-old infarction. Circulation 121:293–305. doi:10.1161/CIRCULATIONAHA.109.871905 CIRCULATIONAHA.109.871905 [pii]

    Article  PubMed  PubMed Central  Google Scholar 

  44. Leor J, Patterson M, Quinones MJ, Kedes LH, Kloner RA (1996) Transplantation of fetal myocardial tissue into the infarcted myocardium of rat. A potential method for repair of infarcted myocardium? Circulation 94:II332–II336

    CAS  PubMed  Google Scholar 

  45. Kikuchi K (2015) Dedifferentiation, transdifferentiation, and proliferation: mechanisms underlying cardiac muscle regeneration in zebrafish. Curr Pathobiol Rep 3:81–88. doi:10.1007/s40139-015-0063-5 63 [pii]

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. 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 U S A 106:14022–14027. doi:10.1073/pnas.0903201106 0903201106 [pii]

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Williams AR, Suncion VY, McCall F, Guerra D, Mather J, Zambrano JP, Heldman AW, Hare JM (2013) Durable scar size reduction due to allogeneic mesenchymal stem cell therapy regulates whole-chamber remodeling. J Am Heart Assoc 2:e000140. doi:10.1161/JAHA.113.000140 2/3/e000140 [pii]

    Article  PubMed  PubMed Central  Google Scholar 

  48. Hatzistergos KE, Quevedo H, Oskouei BN, Hu Q, Feigenbaum GS, Margitich IS, Mazhari R, Boyle AJ, Zambrano JP, Rodriguez JE, Dulce R, Pattany PM, Valdes D, Revilla C, Heldman AW, McNiece I, Hare JM (2010) Bone marrow mesenchymal stem cells stimulate cardiac stem cell proliferation and differentiation. Circ Res 107:913–922. doi:10.1161/CIRCRESAHA.110.222703 CIRCRESAHA.110.222703 [pii]

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Suzuki G, Iyer V, Lee TC, Canty JM Jr (2011) Autologous mesenchymal stem cells mobilize cKit+ and CD133+ bone marrow progenitor cells and improve regional function in hibernating myocardium. Circ Res 109:1044–1054. doi:10.1161/CIRCRESAHA.111.245969 CIRCRESAHA.111.245969 [pii]

    Article  CAS  PubMed  Google Scholar 

  50. Yau TM, Tomita S, Weisel RD, Jia ZQ, Tumiati LC, Mickle DA, Li RK (2003) Beneficial effect of autologous cell transplantation on infarcted heart function: comparison between bone marrow stromal cells and heart cells. Ann Thorac Surg 75:169–176

    Article  PubMed  Google Scholar 

  51. Bolli R, Tang XL, Sanganalmath SK, Rimoldi O, Mosna F, Abdel-Latif A, Jneid H, Rota M, Leri A, Kajstura J (2013) Intracoronary delivery of autologous cardiac stem cells improves cardiac function in a porcine model of chronic ischemic cardiomyopathy. Circulation 128:122–131. doi:10.1161/CIRCULATIONAHA.112.001075 CIRCULATIONAHA.112.001075 [pii]

    Article  CAS  PubMed  Google Scholar 

  52. Williams AR, Hatzistergos KE, Addicott B, McCall F, Carvalho D, Suncion V, Morales AR, Da SJ, Sussman MA, Heldman AW, Hare JM (2013) Enhanced effect of combining human cardiac stem cells and bone marrow mesenchymal stem cells to reduce infarct size and to restore cardiac function after myocardial infarction. Circulation 127:213–223. doi:10.1161/CIRCULATIONAHA.112.131110 CIRCULATIONAHA.112.131110 [pii]

    Article  PubMed  Google Scholar 

  53. Heldman AW, DiFede DL, Fishman JE, Zambrano JP, Trachtenberg BH, Karantalis V, Mushtaq M, Williams AR, Suncion VY, McNiece IK, Ghersin E, Soto V, Lopera G, Miki R, Willens H, Hendel R, Mitrani R, Pattany P, Feigenbaum G, Oskouei B, Byrnes J, Lowery MH, Sierra J, Pujol MV, Delgado C, Gonzalez PJ, Rodriguez JE, Bagno LL, Rouy D, Altman P, Foo CW, Da SJ, Anderson E, Schwarz R, Mendizabal A, Hare JM (2014) Transendocardial mesenchymal stem cells and mononuclear bone marrow cells for ischemic cardiomyopathy: the TAC-HFT randomized trial. JAMA 311:62–73. doi:10.1001/jama.2013.282909 1780025 [pii]

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. 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 FC, Ruiz P, Amador A, Da SJ, McNiece IK, Heldman AW, George R, Lardo A (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 308:2369–2379. doi:10.1001/jama.2012.25321 1388858 [pii]

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Mushtaq M, DL DF, Golpanian S, Khan A, SA G, Mendizabal A, AW H, JM H (2014) Rationale and design of the Percutaneous Stem Cell Injection Delivery Effects on Neomyogenesis in Dilated Cardiomyopathy (the POSEIDON-DCM study): a phase I/II, randomized pilot study of the comparative safety and efficacy of transendocardial injection of autologous mesenchymal stem cell vs. allogeneic mesenchymal stem cells in patients with non-ischemic dilated cardiomyopathy. J Cardiovasc Transl Res 7:769–780. doi:10.1007/s12265-014-9594-0

    Article  PubMed  PubMed Central  Google Scholar 

  56. Karantalis V, DiFede DL, Gerstenblith G, Pham S, Symes J, Zambrano JP, Fishman J, Pattany P, McNiece I, Conte J, Schulman S, Wu K, Shah A, Breton E, Davis-Sproul J, Schwarz R, Feigenbaum G, Mushtaq M, Suncion VY, Lardo AC, Borrello I, Mendizabal A, Karas TZ, Byrnes J, Lowery M, Heldman AW, Hare JM (2014) Autologous mesenchymal stem cells produce concordant improvements in regional function, tissue perfusion, and fibrotic burden when administered to patients undergoing coronary artery bypass grafting: The Prospective Randomized Study of Mesenchymal Stem Cell Therapy in Patients Undergoing Cardiac Surgery (PROMETHEUS) trial. Circ Res 114:1302–1310. doi:10.1161/CIRCRESAHA.114.303180 CIRCRESAHA.114.303180 [pii]

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Leistner DM, Fischer-Rasokat U, Honold J, Seeger FH, Schachinger V, Lehmann R, Martin H, Burck I, Urbich C, Dimmeler S, Zeiher AM, Assmus B (2011) Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction (TOPCARE-AMI): final 5-year results suggest long-term safety and efficacy. Clin Res Cardiol 100:925–934. doi:10.1007/s00392-011-0327-y

    Article  PubMed  Google Scholar 

  58. Huikuri HV, Kervinen K, Niemela M, Ylitalo K, Saily M, Koistinen P, Savolainen ER, Ukkonen H, Pietila M, Airaksinen JK, Knuuti J, Makikallio TH (2008) Effects of intracoronary injection of mononuclear bone marrow cells on left ventricular function, arrhythmia risk profile, and restenosis after thrombolytic therapy of acute myocardial infarction. Eur Heart J 29:2723–2732. doi:10.1093/eurheartj/ehn436 ehn436 [pii]

    Article  PubMed  Google Scholar 

  59. Menasche P, Alfieri O, Janssens S, McKenna W, Reichenspurner H, Trinquart L, Vilquin JT, Marolleau JP, Seymour B, Larghero J, Lake S, Chatellier G, Solomon S, Desnos M, Hagege AA (2008) The myoblast autologous grafting in ischemic cardiomyopathy (MAGIC) trial: first randomized placebo-controlled study of myoblast transplantation. Circulation 117:1189–1200. doi:10.1161/CIRCULATIONAHA.107.734103 CIRCULATIONAHA.107.734103 [pii]

    Article  PubMed  Google Scholar 

  60. Naveiro-Rilo JC, Diez-Juarez DM, Romero BA, Rebollo-Gutierrez F, Rodriguez-Martinez A, Rodriguez-Garcia MA (2010) Validation of the Minnesota living with heart failure questionnaire in primary care. Rev Esp Cardiol 63:1419–1427 13188303 [pii]

    Article  PubMed  Google Scholar 

  61. Yoon YS, Park JS, Tkebuchava T, Luedeman C, Losordo DW (2004) Unexpected severe calcification after transplantation of bone marrow cells in acute myocardial infarction. Circulation 109:3154–3157. doi:10.1161/01.CIR.0000134696.08436.65 01.CIR.0000134696.08436.65 [pii]

    Article  PubMed  Google Scholar 

  62. Breitbach M, Bostani T, Roell W, Xia Y, Dewald O, Nygren JM, Fries JW, Tiemann K, Bohlen H, Hescheler J, Welz A, Bloch W, Jacobsen SE, Fleischmann BK (2007) Potential risks of bone marrow cell transplantation into infarcted hearts. Blood 110:1362–1369. doi:10.1182/blood-2006-12-063412 blood-2006-12-063412 [pii]

    Article  CAS  PubMed  Google Scholar 

  63. Cho HJ, Lee N, Lee JY, Choi YJ, Ii M, Wecker A, Jeong JO, Curry C, Qin G, Yoon YS (2007) Role of host tissues for sustained humoral effects after endothelial progenitor cell transplantation into the ischemic heart. J Exp Med 204:3257–3269. doi:10.1084/jem.20070166 jem.20070166 [pii]

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Forte G, Minieri M, Cossa P, Antenucci D, Sala M, Gnocchi V, Fiaccavento R, Carotenuto F, De VP, Baldini PM, Prat M, Di NP (2006) Hepatocyte growth factor effects on mesenchymal stem cells: proliferation, migration, and differentiation. Stem Cells 24:23–33. doi:10.1634/stemcells.2004-0176 2004-0176 [pii]

    Article  CAS  PubMed  Google Scholar 

  65. Urbanek K, Rota M, Cascapera S, Bearzi C, Nascimbene A, De AA, Hosoda T, Chimenti S, Baker M, Limana F, Nurzynska D, Torella D, Rotatori F, Rastaldo R, Musso E, Quaini F, Leri A, Kajstura J, Anversa P (2005) Cardiac stem cells possess growth factor-receptor systems that after activation regenerate the infarcted myocardium, improving ventricular function and long-term survival. Circ Res 97:663–673. doi:10.1161/01.RES.0000183733.53101.11 01.RES.0000183733.53101.11 [pii]

    Article  CAS  PubMed  Google Scholar 

  66. Zhang M, Methot D, Poppa V, Fujio Y, Walsh K, Murry CE (2001) Cardiomyocyte grafting for cardiac repair: graft cell death and anti-death strategies. J Mol Cell Cardiol 33:907–921. doi:10.1006/jmcc.2001.1367 S0022-2828(01)91367-7 [pii]

    Article  CAS  PubMed  Google Scholar 

  67. Osborne J, Hellein J, Singla R, Singal PK, Singla DK (2015) Stem cells in three-dimensional bioprinting: future perspectives. Curr Res Cardiol 2:1–4

    Article  Google Scholar 

Download references

Acknowledgment

The authors would like to thank Abed Naser for his artistic contributions.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Dinender K. Singla Ph.D., F.A.H.A., F.I.A.C.S. .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer Science+Business Media LLC

About this protocol

Cite this protocol

Johnson, T.A., Singla, D.K. (2017). Therapeutic Application of Adult Stem Cells in the Heart. In: Di Nardo, P., Dhingra, S., Singla, D. (eds) Adult Stem Cells. Methods in Molecular Biology, vol 1553. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6756-8_20

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-6756-8_20

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-6754-4

  • Online ISBN: 978-1-4939-6756-8

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics