Advertisement

Technology Platforms for Heart Regenerative Therapy Using Pluripotent Stem Cells

  • Fumiyuki Hattori
Chapter
Part of the Stem Cells and Cancer Stem Cells book series (STEM, volume 7)

Abstract

Heart failure is a common, disabling, and deadly disease affecting over 23 million people worldwide. The prevalence of this disease continues to increase each year despite substantial advances in pharmacological treatments and mechanical assistance. Heart transplantation is the ultimate treatment for severe refractory heart failure. However, it benefits only a small proportion of patients because of the limited number of donors and significant surgical invasion. Heart regenerative-cell therapy thus presents a promising alternative strategy. Pluripotent stem cells (PSCs) including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) could provide mass-production cell sources for such therapies because they can theoretically self-renew indefinitely. Currently, iPSCs are intensively studied because they are more easily derived from somatic cells than ESCs, carry fewer ethical concerns, and have potentially wider applications including autologous cell therapies. However, technical concerns remain with the use of iPSCs.

A xenofree culture system would be ideal for therapeutically applied PSCs, although such culture systems still have limited compatibility with many cell lines. To improve this, we have developed a simple preparation method for culturing autogeneic feeder cells from each PSC line. Potential tumorigenicity also remains a major obstacle to clinical applications for PSCs. For heart regenerative therapy, purifying differentiated cardiomyocytes would be a reasonable approach for eliminating undifferentiated cells and retaining only therapeutic cells. To this end, we have established a nongenetic method for PSC purification using mitochondrial marker dyes. Finally, transplantation and efficient survival of PSC-derived cardiomyocytes has proven difficult and it depends on the method of cell preparation. Recently, washout and anoikis were identified as factors underlying the disappearance of injected cardiomyocytes from heart. We have now also developed a simple and efficient way to achieve over 90% survival of injected cardiomyocytes in the host heart. This chapter will lastly discuss new obstacles and future divergent directions for PSCs in heart regenerative therapy.

Keywords

Pluripotent Stem Cell Embryoid Body Mammalian Heart Heart Regeneration Host Myocardium 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. Adams JD, Fedoruk LM, Tache-Leon CA, Peeler BB, Kern JA, Tribble CG, Bergin JD, Kron IL (2006) Does preoperative ejection fraction predict operative mortality with left ventricular restoration? Ann Thorac Surg 82:1715–1719PubMedCrossRefGoogle Scholar
  2. Akopian V, Andrews PW, Beil S, Benvenisty N, Brehm J, Christie M, Ford A, Fox V, Gokhale PJ, Healy L, Holm F, Hovatta O, Knowles BB, Ludwig TE, McKay RD, Miyazaki T, Nakatsuji N, Oh SK, Pera MF, Rossant J, Stacey GN, Suemori H (2010) Comparison of defined culture systems for feeder cell free propagation of human embryonic stem cells. In Vitro Cell Dev Biol Anim 46:247–258PubMedCentralPubMedCrossRefGoogle Scholar
  3. Amit M, Itskovitz-Eldor J (2006) Feeder-free culture of human embryonic stem cells. Methods Enzymol 420:37–49PubMedGoogle Scholar
  4. Amit M, Chebath J, Margulets V, Laevsky I, Miropolsky Y, Shariki K, Peri M, Blais I, Slutsky G, Revel M, Itskovitz-Eldor J (2010) Suspension culture of undifferentiated human embryonic and induced pluripotent stem cells. Stem Cell Rev 6(2):248–259PubMedCrossRefGoogle Scholar
  5. Bettencourt-Dias M, Mittnacht S, Brockes JP (2003) Heterogeneous proliferative potential in regenerative adult newt cardiomyocytes. J Cell Sci 116(Pt 19):4001–4009PubMedCrossRefGoogle Scholar
  6. Bock C, Kiskinis E, Verstappen G, Gu H, Boulting G, Smith ZD, Ziller M, Croft GF, Amoroso MW, Oakley DH, Gnirke A, Eggan K, Meissner A (2011) Reference maps of human ESC and iPS variation enable high-throughput characterization of pluripotent cell lines. Cell 144(3):439–452PubMedCentralPubMedCrossRefGoogle Scholar
  7. Burggren WW, Bicudo JE, Glass ML, Abe AS (1992) Development of blood pressure and cardiac reflexes in the frog Pseudis paradoxsus. Am J Physiol 263(3 Pt 2):R602–R608PubMedGoogle Scholar
  8. Catalina P, Montes R, Ligero G, Sanchez L, de la Cueva T, Bueno C, Leone PE, Menendez P (2008) Human ESCs predisposition to karyotypic instability: is a matter of culture adaptation or differential vulnerability among hESC lines due to inherent properties? Mol Cancer 7:76PubMedCentralPubMedCrossRefGoogle Scholar
  9. Choo A, Padmanabhan J, Chin A, Fong WJ, Oh SK (2006) Immortalized feeders for the scale-up of human embryonic stem cells in feeder and feeder-free conditions. J Biotechnol 122(1):130–141PubMedCrossRefGoogle Scholar
  10. Gonzalez-Rosa JM, Martin V, Peralta M, Torres M, Mercader N (2011) Extensive scar formation and regression during heart regeneration after cryoinjury in zebrafish. Development 138(9):1663–1674PubMedCrossRefGoogle Scholar
  11. Gore A, Li Z, Fung HL, Young JE, Agarwal S, Antosiewicz-Bourget J, Canto I, Giorgetti A, Israel MA, Kiskinis E, Lee JH, Loh YH, Manos PD, Montserrat N, Panopoulos AD, Ruiz S, Wilbert ML, Yu J, Kirkness EF, Izpisua Belmonte JC, Rossi DJ, Thomson JA, Eggan K, Daley GQ, Goldstein LS, Zhang K (2011) Somatic coding mutations in human induced pluripotent stem cells. Nature 471(7336):63–67PubMedCentralPubMedCrossRefGoogle Scholar
  12. Harrison NJ, Baker D, Andrews PW (2007) Culture adaptation of embryonic stem cells echoes germ cell malignancy. Int J Androl 30(4):275–281, discussion 281PubMedCrossRefGoogle Scholar
  13. Hattori F, Chen H, Yamashita H, Tohyama S, Satoh YS, Yuasa S, Li W, Yamakawa H, Tanaka T, Onitsuka T, Shimoji K, Ohno Y, Egashira T, Kaneda R, Murata M, Hidaka K, Morisaki T, Sasaki E, Suzuki T, Sano M, Makino S, Oikawa S, Fukuda K (2010) Nongenetic method for purifying stem cell-derived cardiomyocytes. Nat Methods 7(1):61–66PubMedCrossRefGoogle Scholar
  14. Hervant F, Mathieu J, Durand J (2001) Behavioural, physiological and metabolic responses to long-term starvation and refeeding in a blind cave-dwelling (Proteus anguinus) and a surface-dwelling (Euproctus asper) salamander. J Exp Biol 204(Pt 2):269–281PubMedGoogle Scholar
  15. Hicks JW, Ishimatsu A, Molloi S, Erskin A, Heisler N (1996) The mechanism of cardiac shunting in reptiles: a new synthesis. J Exp Biol 199(Pt 6):1435–1446PubMedGoogle Scholar
  16. Hussein SM, Batada NN, Vuoristo S, Ching RW, Autio R, Narva E, Ng S, Sourour M, Hamalainen R, Olsson C, Lundin K, Mikkola M, Trokovic R, Peitz M, Brustle O, Bazett-Jones DP, Alitalo K, Lahesmaa R, Nagy A, Otonkoski T (2011) Copy number variation and selection during reprogramming to pluripotency. Nature 471(7336):58–62PubMedCrossRefGoogle Scholar
  17. Jopling C, Sleep E, Raya M, Marti M, Raya A, Belmonte JC (2010) Zebrafish heart regeneration occurs by cardiomyocyte dedifferentiation and proliferation. Nature 464(7288):606–609PubMedCentralPubMedCrossRefGoogle Scholar
  18. Kikuchi K, Holdway JE, Major RJ, Blum N, Dahn RD, Begemann G, Poss KD (2011) Retinoic acid production by endocardium and epicardium is an injury response essential for zebrafish heart regeneration. Dev Cell 20(3):397–404PubMedCentralPubMedCrossRefGoogle Scholar
  19. Laube F, Heister M, Scholz C, Borchardt T, Braun T (2006) Re-programming of newt cardiomyocytes is induced by tissue regeneration. J Cell Sci 119(Pt 22):4719–4729PubMedCrossRefGoogle Scholar
  20. Lee JB, Lee JE, Park JH, Kim SJ, Kim MK, Roh SI, Yoon HS (2005) Establishment and maintenance of human embryonic stem cell lines on human feeder cells derived from uterine endometrium under serum-free condition. Biol Reprod 72(1):42–49PubMedCrossRefGoogle Scholar
  21. Lister R, Pelizzola M, Kida YS, Hawkins RD, Nery JR, Hon G, Antosiewicz-Bourget J, O’Malley R, Castanon R, Klugman S, Downes M, Yu R, Stewart R, Ren B, Thomson JA, Evans RM, Ecker JR (2011) Hotspots of aberrant epigenomic reprogramming in human induced pluripotent stem cells. Nature 471(7336):68–73PubMedCentralPubMedCrossRefGoogle Scholar
  22. McDonnell TJ, Oberpriller JO (1983) The atrial proliferative response following partial ventricular amputation in the heart of the adult newt. A light and electron microscopic autoradiographic study. Tissue Cell 15(3):351–363PubMedCrossRefGoogle Scholar
  23. Michel C, Yamada T (1974) Cellular studies of X-ray induced inhibition of lens regeneration. Differentiation 2(4):193–201PubMedCrossRefGoogle Scholar
  24. Minerick AR, Chang HC, Hoagland TM, Olson KR (2003) Dynamic synchronization analysis of venous pressure-driven cardiac output in rainbow trout. Am J Physiol Regul Integr Comp Physiol 285(4):R889–R896PubMedGoogle Scholar
  25. Moore JC, Fu J, Chan YC, Lin D, Tran H, Tse HF, Li RA (2008) Distinct cardiogenic preferences of two human embryonic stem cell (hESC) lines are imprinted in their proteomes in the pluripotent state. Biochem Biophys Res Commun 372(4):553–558PubMedCentralPubMedCrossRefGoogle Scholar
  26. Nadal-Ginard B, Kajstura J, Leri A, Anversa P (2003) Myocyte death, growth, and regeneration in cardiac hypertrophy and failure. Circ Res 92(2):139–150PubMedCrossRefGoogle Scholar
  27. Novak CM, Jiang X, Wang C, Teske JA, Kotz CM, Levine JA (2005) Caloric restriction and physical activity in zebrafish (Danio rerio). Neurosci Lett 383(1–2):99–104PubMedCrossRefGoogle Scholar
  28. Passier R, van Laake LW, Mummery CL (2008) Stem-cell-based therapy and lessons from the heart. Nature 453(7193):322–329PubMedCrossRefGoogle Scholar
  29. Ringer RK, Weiss HS, Sturkie PD (1955) Effect of sex and age on blood pressure in the duck and pigeon. Am J Physiol 183(1):141–143PubMedGoogle Scholar
  30. Salo E, Baguna J (1985) Cell movement in intact and regenerating planarians. Quantitation using chromosomal, nuclear and cytoplasmic markers. J Embryol Exp Morphol 89:57–70PubMedGoogle Scholar
  31. Schmelting B, Niehoff M, Egner B, Korte SH, Weinbauer GF (2009) High Definition Oscillometry: a novel technique for non-invasive blood pressure monitoring in the cynomolgus monkey (Macaca fascicularis). J Med Primatol 38(5):293–301PubMedCrossRefGoogle Scholar
  32. Sedmera D, Pexieder T, Vuillemin M, Thompson RP, Anderson RH (2000) Developmental patterning of the myocardium. Anat Rec 258(4):319–337PubMedCrossRefGoogle Scholar
  33. Singh BN, Koyano-Nakagawa N, Garry JP, Weaver CV (2010) Heart of newt: a recipe for regeneration. J Cardiovasc Transl Res 3(4):397–409PubMedCrossRefGoogle Scholar
  34. Stinner JN, Ely DL (1993) Blood pressure during routine activity, stress, and feeding in black racer snakes (Coluber constrictor). Am J Physiol 264(1 Pt 2):R79–R84PubMedGoogle Scholar
  35. Stojkovic P, Lako M, Stewart R, Przyborski S, Armstrong L, Evans J, Murdoch A, Strachan T, Stojkovic M (2005) An autogeneic feeder cell system that efficiently supports growth of undifferentiated human embryonic stem cells. Stem Cells 23(3):306–314PubMedCrossRefGoogle Scholar
  36. Ueno T, Sakata R, Iguro Y, Yamamoto H, Ueno M, Matsumoto K (2007) Mid-term changes of left ventricular geometry and function after Dor, SAVE, and overlapping procedures. Eur J Cardiothorac Surg 32(1):52–57PubMedCrossRefGoogle Scholar
  37. Unger C, Gao S, Cohen M, Jaconi M, Bergstrom R, Holm F, Galan A, Sanchez E, Irion O, Dubuisson JB, Giry-Laterriere M, Salmon P, Simon C, Hovatta O, Feki A (2009) Immortalized human skin fibroblast feeder cells support growth and maintenance of both human embryonic and induced pluripotent stem cells. Hum Reprod 24(10):2567–2581PubMedCrossRefGoogle Scholar
  38. Wang J, Panakova D, Kikuchi K, Holdway JE, Gemberling M, Burris JS, Singh SP, Dickson AL, Lin YF, Sabeh MK, Werdich AA, Yelon D, Macrae CA, Poss KD (2011) The regenerative capacity of zebrafish reverses cardiac failure caused by genetic cardiomyocyte depletion. Development 138(16):3421–3430PubMedCentralPubMedCrossRefGoogle Scholar
  39. Wertz RL, Donaldson DJ, Mason JM (1976) X-ray induced inhibition of DNA synthesis and mitosis in internal tissues during the initiation of limb regeneration in the adult newt. J Exp Zool 198(2):253–259PubMedCrossRefGoogle Scholar
  40. Yamashita H, Li W, Hattori F, Chen H, Tohyama S, Satoh Y, Sasaki E, Yuasa S, Makino S, Sano M, Fukuda K (2011) Simple autogeneic feeder cell preparation for pluripotent stem cells. Stem Cell Res 6(1):83–89PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  1. 1.Department of CardiologyKeio University School of MedicineTokyoJapan

Personalised recommendations