Mesenchymal stem cells rescue cardiomyoblasts from cell death in an in vitro ischemia model via direct cell-to-cell connections.
BACKGROUND
Bone marrow derived mesenchymal stem cells (MSCs) are promising candidates for cell based therapies in myocardial infarction. However, the exact underlying cellular mechanisms are still not fully understood. Our aim was to explore the possible role of direct cell-to-cell interaction between ischemic H9c2 cardiomyoblasts and normal MSCs. Using an in vitro ischemia model of 150 minutes of oxygen glucose deprivation we investigated cell viability and cell interactions with confocal microscopy and flow cytometry.


RESULTS
Our model revealed that adding normal MSCs to the ischemic cell population significantly decreased the ratio of dead H9c2 cells (H9c2 only: 0.85 +/- 0.086 vs. H9c2+MSCs: 0.16 +/- 0.035). This effect was dependent on direct cell-to-cell contact since co-cultivation with MSCs cultured in cell inserts did not exert the same beneficial effect (ratio of dead H9c2 cells: 0.90 +/- 0.055). Confocal microscopy revealed that cardiomyoblasts and MSCs frequently formed 200-500 nm wide intercellular connections and cell fusion rarely occurred between these cells.


CONCLUSIONS
Based on these results we hypothesize that mesenchymal stem cells may reduce the number of dead cardiomyoblasts after ischemic damage via direct cell-to-cell interactions and intercellular tubular connections may play an important role in these processes.
Cselenyák
Attila
A
Institute of Human Physiology and Clinical Experimental Research, Semmelweis University, H-1094, Tuzoltó utca 37-47, Budapest, Hungary. attila.cselenyak@tissueengineering.hu
Pankotai
Eszter
E
Horváth
Eszter M
EM
Kiss
Levente
L
Lacza
Zsombor
Z
D000818:Animals; D002450:Cell Communication; D016923:Cell Death; D015687:Cell Hypoxia; D002460:Cell Line; D005434:Flow Cytometry; D005947:Glucose / Q000378:metabolism; D007511:Ischemia; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism; D051381:Rats; D015424:Reperfusion
D005947:Glucose
Ann Hematol. 2005 Oct;84(11):715-21
16096830
Stem Cells. 2008 Jan;26(1):244-53
17932424
FASEB J. 2006 May;20(7):950-2
16585061
Eur J Cardiothorac Surg. 2005 Nov;28(5):685-91
16194609
Clin Med (Lond). 2004 Jan-Feb;4(1):13-8
14998260
Semin Thorac Cardiovasc Surg. 2008 Summer;20(2):87-93
18707639
Am J Physiol Heart Circ Physiol. 2004 Oct;287(4):H1599-608
15165986
Adv Drug Deliv Rev. 2008 Jan 14;60(2):277-85
18006178
Stem Cells. 2008 Nov;26(11):2884-92
18687994
Circ Res. 2006 Jun 9;98(11):1414-21
16690882
J Cell Physiol. 2007 Apr;211(1):27-35
17226788
Nature. 2001 Apr 5;410(6829):701-5
11287958
Circulation. 2005 Jul 12;112(2):214-23
15998673
J Tissue Eng Regen Med. 2008 Jun;2(4):169-83
18493906
Circ Res. 2005 May 27;96(10):1039-41
15879310
Biochem Biophys Res Commun. 2007 Nov 23;363(3):674-9
17904522
Am J Physiol Heart Circ Physiol. 2006 Aug;291(2):H886-93
16603697
Nat Med. 2004 May;10(5):494-501
15107841
Cardiovasc Res. 2005 Oct 1;68(1):37-46
15964558
Sci STKE. 2005 Dec 06;2005(313):pe55
16333019
Proc Natl Acad Sci U S A. 2006 Jan 31;103(5):1283-8
16432190
Exp Cell Res. 2004 May 1;295(2):395-406
15093739
Circ Res. 2008 Nov 21;103(11):1204-19
19028920
Cardiovasc Revasc Med. 2007 Jan-Mar;8(1):43-51
17293268
Arthroscopy. 2003 Mar;19(3):310-3
12627157
Arterioscler Thromb Vasc Biol. 2008 Feb;28(2):208-16
17951319
J Immunol. 2004 Aug 1;173(3):1511-3
15265877
Circ Res. 2005 Jan 7;96(1):127-37
15569828
Nature. 2003 Oct 30;425(6961):968-73
14555960
Circulation. 2006 Mar 14;113(10):1275-7
16534026
J Cell Mol Med. 2008 Sep-Oct;12(5A):1622-31
18088382
Circulation. 2004 Oct 26;110(17):2658-65
15492307
Circ Res. 2004 Mar 19;94(5):678-85
14739163
Brain Res Brain Res Protoc. 2003 Jul;11(3):145-54
12842219
Br Med Bull. 2008;87:31-47
18790825
Eur Heart J. 2006 Jan;27(1):107-13
16204263
Nature. 2004 Apr 8;428(6983):664-8
15034593