Nanotubular Crosstalk with Distressed Cardiomyocytes Stimulates the Paracrine Repair Function of Mesenchymal Stem Cells

被引:100
作者
Figeac, Florence [1 ,2 ]
Lesault, Pierre-Francois [1 ,2 ,3 ]
Le Coz, Olivier [1 ,2 ]
Damy, Thibaud [1 ,2 ,4 ]
Souktani, Richard [1 ,2 ,5 ]
Trebeau, Celine [1 ,2 ]
Schmitt, Alain [6 ,7 ,8 ]
Ribot, Jonathan [1 ,2 ]
Mounier, Remi [6 ,7 ,8 ]
Guguin, Aurelie [1 ,2 ]
Manier, Celine [1 ,2 ,9 ,10 ]
Surenaud, Mathieu [1 ,2 ,9 ,10 ]
Hittinger, Luc [1 ,2 ]
Dubois-Rande, Jean-Luc [1 ,2 ,4 ]
Rodriguez, Anne-Marie [1 ,2 ]
机构
[1] Hop Henri Mondor, INSERM, U955, F-94010 Creteil, France
[2] Univ Paris Est, UPEC, UMR S955, Creteil, France
[3] Hop Henri Mondor, Assistance Publ Hop Paris, Serv Physiol Explorat Fonct, F-94010 Creteil, France
[4] Hop Henri Mondor A Chenevier, AP HP, Creteil, France
[5] INSERM, U955, F Creteil, France
[6] Inst Cochin Genet Mol, INSERM, U1016, F-75014 Paris, France
[7] CNRS, UMR8104, Paris, France
[8] Univ Paris 05, Sorbonne Paris Cite, Paris, France
[9] Hop Henri Mondor A Chenevier, AP HP, MIC, Creteil, France
[10] Hop Henri Mondor A Chenevier, AP HP, Vaccine Res Inst, Creteil, France
关键词
Mesenchymal stem cells; Cell therapy; Myocardial infarction; Tunneling nanotubes; Stem paracrine function; ENDOTHELIAL PROGENITOR CELLS; BONE-MARROW; ISCHEMIC-HEART; IN-VITRO; TRANSPLANTATION; THERAPY; DIFFERENTIATION; ANGIOGENESIS; MOBILIZATION; ENGRAFTMENT;
D O I
10.1002/stem.1560
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Mesenchymal stem cells (MSC) are known to repair broken heart tissues primarily through a paracrine fashion while emerging evidence indicate that MSC can communicate with cardiomyocytes (CM) through tunneling nanotubes (TNT). Nevertheless, no link has been so far established between these two processes. Here, we addressed whether cell-to-cell communication processes between MSC and suffering cardiomyocytes and more particularly those involving TNT control the MSC paracrine regenerative function. In the attempt to mimic in vitro an injured heart microenvironment, we developed a species mismatch coculture system consisting of terminally differentiated CM from mouse in a distressed state and human multipotent adipose derived stem cells (hMADS). In this setting, we found that crosstalk between hMADS and CM through TNT altered the secretion by hMADS of cardioprotective soluble factors such as VEGF, HGF, SDF-1, and MCP-3 and thereby maximized the capacity of stem cells to promote angiogenesis and chemotaxis of bone marrow multipotent cells. Additionally, engraftment experiments into mouse infarcted hearts revealed that in vitro preconditioning of hMADS with cardiomyocytes increased the cell therapy efficacy of naive stem cells. In particular, in comparison with hearts treated with stem cells alone, those treated with cocultured ones exhibited greater cardiac function recovery associated with higher angiogenesis and homing of bone marrow progenitor cells at the infarction site. In conclusion, our findings established the first relationship between the paracrine regenerative action of MSC and the nanotubular crosstalk with CM and emphasize that ex vivo manipulation of these communication processes might be of interest for optimizing current cardiac cell therapies. Stem Cells2014;32:216-230
引用
收藏
页码:216 / 230
页数:15
相关论文
共 58 条
  • [41] Autologous mesenchymal stem cells produce reverse remodelling in chronic ischaemic cardiomyopathy
    Schuleri, Karl H.
    Feigenbaum, Gary S.
    Centola, Marco
    Weiss, Eric S.
    Zimmet, Jeffrey M.
    Turney, Jennifer
    Kellner, Joshua
    Zviman, Menekhem M.
    Hatzistergos, Konstantinos E.
    Detrick, Barbara
    Conte, John V.
    McNiece, Ian
    Steenbergen, Charles
    Lardo, Albert C.
    Hare, Joshua M.
    [J]. EUROPEAN HEART JOURNAL, 2009, 30 (22) : 2722 - 2732
  • [42] Comparison of the effects of fetal cardiomyocyte and skeletal myoblast transplantation on postinfarction left ventricular function
    Scorsin, M
    Hagège, A
    Vilquin, JT
    Fiszman, M
    Marotte, F
    Samuel, JL
    Rappaport, L
    Schwartz, K
    Menasché, P
    [J]. JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY, 2000, 119 (06) : 1169 - 1175
  • [43] Mesenchymal stem cell implantation in a swine myocardial infarct model: Engraftment and functional effects
    Shake, JG
    Gruber, PJ
    Baumgartner, WA
    Senechal, G
    Meyers, J
    Redmond, JM
    Pittenger, MF
    Martin, BJ
    [J]. ANNALS OF THORACIC SURGERY, 2002, 73 (06) : 1919 - 1925
  • [44] Pretreatment of Human Mesenchymal Stem Cells with Pioglitazone Improved Efficiency of Cardiomyogenic Transdifferentiation and Cardiac Function
    Shinmura, Daisuke
    Togashi, Ikuko
    Miyoshi, Shunichiro
    Nishiyama, Nobuhiro
    Hida, Naoko
    Tsuji, Hiroko
    Tsuruta, Hikaru
    Segawa, Kaoru
    Tsukada, Yuiko
    Ogawa, Satoshi
    Umezawa, Akihiro
    [J]. STEM CELLS, 2011, 29 (02) : 357 - 366
  • [45] Granulocyte-colony stimulating factor increases donor mesenchymal stem cells in bone marrow and their mobilization into peripheral circulation but does not repair dystrophic heart after bone marrow transplantation
    Tatsumi, Kimiko
    Otani, Hajime
    Sato, Daisuke
    Enoki, Chiharu
    Iwasaka, Toshiji
    Imamura, Hiroji
    Taniuchi, Shoichiro
    Kaneko, Kazunari
    Adachi, Yasushi
    Ikehara, Susumu
    [J]. CIRCULATION JOURNAL, 2008, 72 (08) : 1351 - 1358
  • [46] Human mesenchymal stem cells differentiate to a cardiomyocyte phenotype in the adult murine heart
    Toma, C
    Pittenger, MF
    Cahill, KS
    Byrne, BJ
    Kessler, PD
    [J]. CIRCULATION, 2002, 105 (01) : 93 - 98
  • [47] Improved heart function with myogenesis and angiogenesis after autologous porcine bone marrow stromal cell transplantation
    Tomita, S
    Mickle, DAG
    Weisel, RD
    Jia, ZC
    Tumiati, LC
    Allidina, Y
    Liu, P
    Li, RK
    [J]. JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY, 2002, 123 (06) : 1132 - 1140
  • [48] Bone marrow stem cells prevent left ventricular remodeling of ischemic heart through paracrine signaling
    Uemura, Ryota
    Xu, Meifeng
    Ahmad, Nauman
    Ashraf, Muhammad
    [J]. CIRCULATION RESEARCH, 2006, 98 (11) : 1414 - 1421
  • [49] Signaling factors in stem cell-mediated repair of infarcted myocardium
    Vandervelde, S
    van Luyn, MJA
    Tio, RA
    Harmsen, MC
    [J]. JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 2005, 39 (02) : 363 - 376
  • [50] Stem cell therapy for end-stage heart failure: indispensable role for the cell?
    Vrijsen, K. R.
    Chamuleau, S. A. J.
    Noort, W. A.
    Doevendans, P. A.
    Sluijter, J. P. G.
    [J]. CURRENT OPINION IN ORGAN TRANSPLANTATION, 2009, 14 (05) : 560 - 565