CD45-positive cells are not an essential component in cardiosphere formation
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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.
KeywordsCardiosphere Cardiac progenitor cells Bone marrow CD45+ cells Cell therapy Mouse
We thank Drs. Muhammad Khan, Junya Takagawa and Yan Zhou for technical input and assistance.
CS-forming cells from non-MI heart aggregated together to form cell clusters (cardiospheres) after 35 h in the timelapse system. (AVI 12368 kb)
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)
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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