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Cell and Tissue Research

, Volume 351, Issue 1, pp 201–205 | Cite as

CD45-positive cells are not an essential component in cardiosphere formation

  • Jianqin Ye
  • Andrew J. Boyle
  • Henry Shih
  • Richard E. Sievers
  • Zhi-En Wang
  • Matthew Gormley
  • Yerem YeghiazariansEmail author
Short Communication

Abstract

The cardiosphere (CS) is composed of a heterogeneous population of cells, including CD45+ cells that are bone marrow (BM)-derived. However, whether the CD45+ cells are an essential cell component in CS formation is unknown. The current study was undertaken to address this question. Cardiospheres (CSs) were harvested from 1-week post-myocardial infarction (MI) or non-MI hearts of C57BL/6 J mice. The process of CS formation was observed by timelapse photography. To analyze the role of BM-derived CD45+ cells in CS formation, CD45+ cells were depleted from populations of CS-forming cells by immunomagnetic beads. We recorded the number of CSs formed in culture from the same amount (105) of intact CS-forming cells, from CD45+-cell-depleted CS-forming cells and from CD45+ cells alone (n=6–9/cell type). CS-forming cells selectively aggregated together to form CSs by 35 h after plating. The depletion of CD45+ cells from CS-forming cells actually increased the formation of CSs (67±10 CSs/105 cells) compared with non-depleted CS-forming cells (51±6 CSs/105 cells, P<0.0001). Purified CD45+ cells from CS-forming cells did not form CSs in culture. Thus, BM-derived CD45+ cells including BM progenitors are neither necessary nor sufficient for CS formation.

Keywords

Cardiosphere Cardiac progenitor cells Bone marrow CD45+ cells Cell therapy Mouse 

Notes

Acknowledgements

We thank Drs. Muhammad Khan, Junya Takagawa and Yan Zhou for technical input and assistance.

Disclosure statement

None

Supplementary material

Video S1

CS-forming cells from non-MI heart aggregated together to form cell clusters (cardiospheres) after 35 h in the timelapse system. (AVI 12368 kb)

Video S2

CS-forming cells from 1-week post-MI heart aggregated together to form cell clusters (cardiospheres) after 35 h in the timelapse system. (MOV 54.2 mb)

References

  1. Balsam LB, Wagers AJ, Christensen JL, Kofidis T, Weissman IL, Robbins RC (2004) Haematopoietic stem cells adopt mature haematopoietic fates in ischaemic myocardium. Nature 428:668–673PubMedCrossRefGoogle Scholar
  2. Barile L, Messina E, Giacomello A, Marban E (2007) Endogenous cardiac stem cells. Prog Cardiovasc Dis 50:31–48PubMedCrossRefGoogle Scholar
  3. Beltrami AP, Barlucchi L, Torella D, Baker M, Limana F, Chimenti S, Kasahara H, Rota M, Musso E, Urbanek K, Leri A, Kajstura J, Nadal-Ginard B, Anversa P (2003) Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell 114:763–776PubMedCrossRefGoogle Scholar
  4. Bolli R, Chugh AR, D’Amario D, Loughran JH, Stoddard MF, Ikram S, Beache GM, Wagner SG, Leri A, Hosoda T, Sanada F, Elmore JB, Goichberg P, Cappetta D, Solankhi NK, Fahsah I, Rokosh DG, Slaughter MS, Kajstura J, Anversa P (2011) Cardiac stem cells in patients with ischaemic cardiomyopathy (SCIPIO): initial results of a randomised phase 1 trial. Lancet 378:1847–1857PubMedCrossRefGoogle Scholar
  5. Burger PE, Xiong X, Coetzee S, Salm SN, Moscatelli D, Goto K, Wilson EL (2005) Sca-1 expression identifies stem cells in the proximal region of prostatic ducts with high capacity to reconstitute prostatic tissue. Proc Natl Acad Sci USA 102:7180–7185PubMedCrossRefGoogle Scholar
  6. Weger RA de, Verbrugge I, Bruggink AH, Oosterhout MM van, Souza Y de, Wichen DF van, Gmelig-Meyling FH, Jonge N de, Verdonck LF (2008) Stem cell-derived cardiomyocytes after bone marrow and heart transplantation. Bone Marrow Transplant 41:563–569PubMedCrossRefGoogle Scholar
  7. Edling CE, Hallberg B (2007) c-Kit–a hematopoietic cell essential receptor tyrosine kinase. Int J Biochem Cell Biol 39:1995–1998PubMedCrossRefGoogle Scholar
  8. Ellison GM, Galuppo V, Vicinanza C, Aquila I, Waring CD, Leone A, Indolfi C, Torella D (2010) Cardiac stem and progenitor cell identification: different markers for the same cell? Front Biosci (Schol Ed) 2:641–652CrossRefGoogle Scholar
  9. Kajstura J, Rota M, Whang B, Cascapera S, Hosoda T, Bearzi C, Nurzynska D, Kasahara H, Zias E, Bonafe M, Nadal-Ginard B, Torella D, Nascimbene A, Quaini F, Urbanek K, Leri A, Anversa P (2005) Bone marrow cells differentiate in cardiac cell lineages after infarction independently of cell fusion. Circ Res 96:127–137PubMedCrossRefGoogle Scholar
  10. Kajstura J, Rota M, Hall SR, Hosoda T, D’Amario D, Sanada F, Zheng H, Ogorek B, Rondon-Clavo C, Ferreira-Martins J, Matsuda A, Arranto C, Goichberg P, Giordano G, Haley KJ, Bardelli S, Rayatzadeh H, Liu X, Quaini F, Liao R, Leri A, Perrella MA, Loscalzo J, Anversa P (2011) Evidence for human lung stem cells. N Engl J Med 364:1795–1806PubMedCrossRefGoogle Scholar
  11. Laugwitz KL, Moretti A, Lam J, Gruber P, Chen Y, Woodard S, Lin LZ, Cai CL, Lu MM, Reth M, Platoshyn O, Yuan JX, Evans S, Chien KR (2005) Postnatal Isl1+ cardioblasts enter fully differentiated cardiomyocyte lineages. Nature 433:647–653PubMedCrossRefGoogle Scholar
  12. Leong KG, Wang BE, Johnson L, Gao WQ (2008) Generation of a prostate from a single adult stem cell. Nature 456:804–808PubMedCrossRefGoogle Scholar
  13. Makkar RR, Smith RR, Cheng K, Malliaras K, Thomson LE, Berman D, Czer LS, Marban L, Mendizabal A, Johnston PV, Russell SD, Schuleri KH, Lardo AC, Gerstenblith G, Marban E (2012) Intracoronary cardiosphere-derived cells for heart regeneration after myocardial infarction (CADUCEUS): a prospective, randomised phase 1 trial. Lancet 379:895–904PubMedCrossRefGoogle Scholar
  14. Martin CM, Meeson AP, Robertson SM, Hawke TJ, Richardson JA, Bates S, Goetsch SC, Gallardo TD, Garry DJ (2004) Persistent expression of the ATP-binding cassette transporter, Abcg2, identifies cardiac SP cells in the developing and adult heart. Dev Biol 265:262–275PubMedCrossRefGoogle Scholar
  15. Matsuura K, Nagai T, Nishigaki N, Oyama T, Nishi J, Wada H, Sano M, Toko H, Akazawa H, Sato T, Nakaya H, Kasanuki H, Komuro I (2004) Adult cardiac Sca-1-positive cells differentiate into beating cardiomyocytes. J Biol Chem 279:11384–11391PubMedCrossRefGoogle Scholar
  16. Messina E, De Angelis L, Frati G, Morrone S, Chimenti S, Fiordaliso F, Salio M, Battaglia M, Latronico MV, Coletta M, Vivarelli E, Frati L, Cossu G, Giacomello A (2004) Isolation and expansion of adult cardiac stem cells from human and murine heart. Circ Res 95:911–921PubMedCrossRefGoogle Scholar
  17. Miyamoto S, Kawaguchi N, Ellison GM, Matsuoka R, Shin’oka T, Kurosawa H (2010) Characterization of long-term cultured c-kit+cardiac stem cells derived from adult rat hearts. Stem Cells Dev 19:105–116PubMedCrossRefGoogle Scholar
  18. Murry CE, Soonpaa MH, Reinecke H, Nakajima H, Nakajima HO, Rubart M, Pasumarthi KB, Virag JI, Bartelmez SH, Poppa V, Bradford G, Dowell JD, Williams DA, Field LJ (2004) Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts. Nature 428:664–668PubMedCrossRefGoogle Scholar
  19. Oh H, Bradfute SB, Gallardo TD, Nakamura T, Gaussin V, Mishina Y, Pocius J, Michael LH, Behringer RR, Garry DJ, Entman ML, Schneider MD (2003) Cardiac progenitor cells from adult myocardium: homing, differentiation, and fusion after infarction. Proc Natl Acad Sci USA 100:12313–12318PubMedCrossRefGoogle Scholar
  20. Orlic D, Kajstura J, Chimenti S, Jakoniuk I, Anderson SM, Li B, Pickel J, McKay R, Nadal-Ginard B, Bodine DM, Leri A, Anversa P (2001) Bone marrow cells regenerate infarcted myocardium. Nature 410:701–705PubMedCrossRefGoogle Scholar
  21. Quaini F, Urbanek K, Beltrami AP, Finato N, Beltrami CA, Nadal-Ginard B, Kajstura J, Leri A, Anversa P (2002) Chimerism of the transplanted heart. N Engl J Med 346:5–15PubMedCrossRefGoogle Scholar
  22. Smith RR, Barile L, Cho HC, Leppo MK, Hare JM, Messina E, Giacomello A, Abraham MR, Marban E (2007) Regenerative potential of cardiosphere-derived cells expanded from percutaneous endomyocardial biopsy specimens. Circulation 115:896–908PubMedCrossRefGoogle Scholar
  23. Spangrude GJ, Heimfeld S, Weissman IL (1988) Purification and characterization of mouse hematopoietic stem cells. Science 241:58–62PubMedCrossRefGoogle Scholar
  24. Tang YL, Shen L, Qian K, Phillips MI (2007) A novel two-step procedure to expand cardiac Sca-1+ cells clonally. Biochem Biophys Res Commun 359:877–883PubMedCrossRefGoogle Scholar
  25. Thiele J, Varus E, Wickenhauser C, Kvasnicka HM, Lorenzen J, Gramley F, Metz KA, Rivero F, Beelen DW (2004) Mixed chimerism of cardiomyocytes and vessels after allogeneic bone marrow and stem-cell transplantation in comparison with cardiac allografts. Transplantation 77:1902–1905PubMedCrossRefGoogle Scholar
  26. Torella D, Ellison GM, Karakikes I, Nadal-Ginard B (2007) Resident cardiac stem cells. Cell Mol Life Sci 64:661–673PubMedCrossRefGoogle Scholar
  27. Wang X, Hu Q, Nakamura Y, Lee J, Zhang G, From AH, Zhang J (2006) The role of the sca-1+/CD31- cardiac progenitor cell population in postinfarction left ventricular remodeling. Stem Cells 24:1779–1788PubMedCrossRefGoogle Scholar
  28. Ye J, Boyle A, Shih H, Sievers RE, Zhang Y, Prasad M, Su H, Zhou Y, Grossman W, Bernstein HS, Yeghiazarians Y (2012) Sca-1 cardiosphere-derived cells are enriched for Isl1-expressing cardiac precursors and improve cardiac function after myocardial injury. PLoS One 7:e30329PubMedCrossRefGoogle Scholar
  29. Yeghiazarians Y, Zhang Y, Prasad M, Shih H, Saini SA, Takagawa J, Sievers RE, Wong ML, Kapasi NK, Mirsky R, Koskenvuo J, Minasi P, Ye J, Viswanathan MN, Angeli FS, Boyle AJ, Springer ML, Grossman W (2009) Injection of bone marrow cell extract into infarcted hearts results in functional improvement comparable to intact cell therapy. Mol Ther 17:1250–1256PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Jianqin Ye
    • 1
  • Andrew J. Boyle
    • 1
    • 2
  • Henry Shih
    • 1
  • Richard E. Sievers
    • 1
  • Zhi-En Wang
    • 4
  • Matthew Gormley
    • 5
  • Yerem Yeghiazarians
    • 1
    • 2
    • 3
    • 6
    Email author
  1. 1.Department of Medicine, Division of CardiologyUniversity of California, San FranciscoSan FranciscoUSA
  2. 2.Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell ResearchUniversity of California, San FranciscoSan FranciscoUSA
  3. 3.Cardiovascular Research InstituteUniversity of California, San FranciscoSan FranciscoUSA
  4. 4.Howard Hughes Medical InstituteUniversity of California, San FranciscoSan FranciscoUSA
  5. 5.Department of Obstetrics, Gynecology and Reproductive BiologyUniversity of California, San FranciscoSan FranciscoUSA
  6. 6.University of California, San FranciscoSan FranciscoUSA

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