Stem Cells International

Review Article

How to Improve the Survival of Transplanted Mesenchymal Stem Cell in Ischemic Heart?

Table 1

Strategies to improve MSC survival in ischemic myocardium.
TreatmentSpeciesCell amountLabeling and measurementSurvivalUnitFold changes (approximately)References
Genetic modification
Bcl-2 overexpressionRat6 × 106BrdU labeling and immunofluorescence4 days3 weeks6 weeksBrdu positive per 1000 nuclei4 days3 weeks6 weeks 
Bcl-2 MSCVector-MSCBcl-2 MSCVector-MSCBcl-2 MSCVector-MSC2.2 fold1.9 fold1.2 fold[90]
3251001805711050 
GATA4 overexpressionRat1.5 × 106SRY gene quantification4 daysCells per mg tissue    
GATA4-MSCVector-MSC2.8 fold[102]
41.4    
HSP20 overexpressionRat1 × 106SRY gene quantification4 daysFold    
Hsp20-MSCGFP-MSC2 fold[94]
21    
Akt overexpressionMouse5 × 105GFP overexpression and immunofluorescence3 days7 days14 daysGFP+ cells3 days7 days14 days 
Akt-MSCGFP-MSCAkt-MSCGFP-MSCAkt-MSCGFP-MSC>2 fold>6 fold>5 fold[18]
5102201001871 
Survivin overexpressionRat2 × 106PCR for GFP7 days  24 daysRatio of GFP/GAPDH7 days 28 days 
Survivin-MSCGFP-MSC  Survivin-MSCGFP-MSC2.5 fold 4.3 fold[96]
0.620.25  0.560.1 
HO-1 overexpressionMouse1 × 106SRY gene quantification4 hours24 hours1 weekImplanted cells4 hours24 hours1 week 
HO-1-MSCLacZ-MSCHO-1-MSCLacZ-MSCHO-1-MSCLacZ-MSC3.5 fold1.5 fold7.5 fold[97]
70%20%20%8%15%2% 
GSK-3βMouse1.5 × 105GFP overexpression and immunofluorescence12 weeksGFPpos cells/mm2    
GSK-3β-GFP-MSCGFP-MSC—[98]
25.80%    
ERBB4 overexpressionMouse3 × 105GFP overexpression and immunofluorescence4 weeksGFPpos cells/mm2    
ERBB4-GFP-MSCGFP-MSC5.6 fold[99]
285    
CCR1 overexpressionMouse3 × 105GFP overexpression and immunofluorescence72 hoursCells/mm2    
CCR1-GFP-MSCGFP-MSC2.5 fold[100]
10042    
mir-1 overexpressionMouse5 × 106SRY gene quantification1 weekCells/mg tissue    
mir-1-MSCMSC2.26 fold[103]
3.4 × 1031.5 × 103    
PHD2 silencingMouse1 × 105GFP overexpression and immunofluorescence4 weeks% of cell delivered    
shPHD2-MSCMSC5.4 fold[102]
0.65 ± 0.09%0.12 ± 0.04%    
SDF-1 overexpressionRat5 × 105DAPI labeling1 weekCells/mm2    
SDF-1-MSCEGFP-MSC4 fold[101]
20055    
sFrp2 overexpressionMouse2.5 × 105GFP counting30 daysCells    
sFrp2-MSCGFP-MSC4 fold[94]
82    
Hydrogel/polymer/scaffold
PNIPAAm + SWCNTs + BMSCRat2 × 106Dil labeling 1 weekCell numbers/filed    
PNIPAAm + SWCNTs + BMSCPBS + BMSC1.5 fold[70]
3321   
Fibrin glue + ADSCRat5 × 106DAPI labeling24 hours% of cell delivered    
Fibrin + ADSCADSC1.4 fold 
19.10 ± 3.13%14.16 ± 2.73%  [78]
4 weeks (grafted size)Grafted size 
Fibrin + ADSCADSC1.96 fold 
11.52 ± 2.34%5.85 ± 1.35    
Alginate + MSCSwine2 × 106Dil labeling 2 weeksArea of engraftment%    
Alginate + MSCMSC4 fold[77]
123    
Fibrin glue + skeletal myoblastRat5 × 106Dil labeling 5 weeks% of the infarcted area    
Fibrin glue + skeletal myoblastBSA + skeletal myoblast2.2 fold[65]
9.7 ± 4.2%4.3 ± 1.5%    
a-Cyclodextrin/(MPEG-PCL-MPEG)Rabbit2 × 107DAPI labeling4 weeksCells/mm2    
a-Cyclodextrin/(MPEG-PCL-MPEG) + MSCMSC2.5 fold[127]
2150 ± 235845 ± 156    
Dex-PCL-HEMA/PNIPAAm + BMMNCRabbit1 × 107DAPI labeling48 hours% of cell delivered    
Dex-PCL-HEMA/PNIPAAm + BMMNCBMMNC1.75 fold[73]
2112    
Patch/cellsSheet
Collagen scaffold loaded with IL-10 plasmidRat—Dil labeling 4 weeksCells/mm2    
Scaffold + IL-10 plasmid + MSCScaffold + MSCScaffold alone>5 fold[75]
132.50    
Collagen patch seeded with ADSCRat3.5 × 105GFP counting1 week (engraftment)% of cell delivered    
Collagen patch seeded with ADSCADSC alone— 
25.3 ± 7.0%0  [80]
1 month (engraftment)% of cell delivered 
Collagen patch seeded with ADSCADSC alone— 
6.4 ± 4%0    
MSC cell sheetRat4 × 106SRY gene quantification3 days28 daysImplanted cells3 days 28 days 
MSC cell sheetMSC injectionMSC cell sheetMSC injection>11 fold >18 fold[128]
56.0 ± 7.2%5.0 ± 1.0%9.1 ± 1.9%0.5 ± 0.2% 
Triple-layer autologous ADSC sheetRat1 × 107GFP counting2 monthsScoring    
Triple-layer autologous ADSC sheetADSC—[60]
2-3 (moderate or large number of cells)0-1 (no or minimal amount of cells)    
Collagen sponge seeded with myoblastRat5 × 107Human gene PCR4 weeks (engraftment)DNA ng/μL (mean [min, max])    
Collagen sponge seeded with myoblastMyoblast cell sheetMyoblast injection—[55]
6.2 [0.00, 17.40]0 [0.00, 88.00]0 [0.00, 2.60]    
Combined therapy
MSC + CS/PC coimplantationRat2 × 108/1 × 106Alu immunofluorescence4 weeksCells/cm3    
MSC + CS/PCMSC aloneCPC alone7 fold[110]
7.520   
Rosuvastatin + MSCMouse1 × 106GFP overexpression and bioluminescence imaging2 weeksPhotons/s/cm2/sr    
Rosuvastatin + MSCMSC alone1.75[119]
0.71 ± 0.02 × 1050.40 ± 0.05 × 105    
Atorvastatin + MSCRat5 × 106SRY gene quantification4 weeksCells/per high power field    
Atorvastatin + MSCMSC alone4 fold[129]
22.0 ± 1.75.7 ± 1.2    
Simvastatin (SIMV) + MSCSwine3 × 107DAPI labeling6 weeksCells/per 5 sections    
SIMV + MSCMSC4~5 fold[113]
310.6 ± 83.870.5 ± 22.3    
LXR agonist T0901317Mouse1 × 106GFP overexpression and bioluminescence imaging4 weeksPhotons/s/cm2/sr    
T0901317 + ADSCADSC alone5.4 fold[130]
0.27 ± 0.05 × 1050.05 ± 0.03 × 105    
IP6Ks inhibitor TNPMouse1 × 106GFP overexpression and immunofluorescence2 weeksCells/mm2    
TNP + MSCMSC alone2.5 fold[131]
366 ± 34.2114 ± 17.8    
Ghrelin pretreatmentMouse7 × 105GFP overexpression and bioluminescence imaging3 weeksPhotons/s/cm2/sr    
ADSC pretreated with grhelinADSC 1.75 fold[132]
0.7 ± 0.02 × 1050.4 ± 0.03 × 105    
Ad-HIF-α + MSCMouse1 × 106SRY gene quantification/bioluminescence imaging3 weeksCell survival rate    
Ad-HIF-α combined with MSCMSC alone2.14 fold[133]
1.50%0.70%    
HGF/VEGF + MSCMouse0.5 × 106Bioluminescence imaging3 days4 daysFold changes3 days4 days 
HGF + MSCMSC aloneVEGF + MSCMSC aloneHGFVEGF[134]
1.67 ± 0.4311.44 ± 0.5511.67 ± 0.431.44 ± 0.55