Table 3.
Cell Source | Isolation Method | Modification | Method | Animal Model | Dose | Administration Route and Time Post-MI | Reparative Effect | Mechanism | Ref |
---|---|---|---|---|---|---|---|---|---|
Cargo loading | |||||||||
Cardiac MSCs | SEC | Notch1 overexpression | Adenovirus | Mouse, permanent | 2×1010 particles | IM, at 10 min |
|
- | [125] |
HEK293T | UC | miR-21 overexpression | - | Mouse, permanent | 20 µg | IM, immediate |
|
PDCD4 | [126] |
Rat BM-MSCs | Exosome Isolation Reagent (RiboBio) |
miR-338 overexpression | Lipofection | Rat, permanent | - | IM, immediate |
|
MAP3K2/JNK pathway | [127] |
Rat BM-MSCs | Exosomes isolation kit (Thermo Fisher Scientific) | miR-301 overexpression | Lipofection | Rat, permanent | - | IM, at 30 min |
|
- | [128] |
Human umbilical cord MSCs | UC | miR-181a overexpression | Lentivirus | Mouse, I/R | 200 µg | IM, at reperfusion |
|
c-Fos inhibition | [129] |
Human BM-MSCs | Total Isolation Reagent (Thermo Fisher Scientific) | miR-101a overexpression | Electroporation | Mouse, permanent | 2 mg/kg | IV, at days 2 and 3 |
|
- | [130] |
Rat ADSCs | ExoQuick-TC (System Biosciences) | miR-126 overexpression | Lipofection | Rat, permanent | 400 µg | IV, immediate |
|
- | [103] |
Human umbilical cord MSCs | UC | SDF1 overexpression | Lipofection | Mouse, permanent | - | IM, immediate |
|
- | [131] |
Human umbilical cord MSCs | UC | TIMP2 overexpression | Lentivirus | Rat, permanent | 50 µg/ml | IM, immediate |
|
Akt/Sfrp2 Pathway | [132] |
Human MSCs | Exosome isolation kit (Invitrogen) | LncRNA KLF3-AS1 overexpression | Lipofection | Rat, permanent | 40 µg | IV, at 1 week |
|
miR-138-5p and Sirt1 | [133] |
Mouse BM-MSCs | ExoQuick TC (SBI) | GATA4 overexpression | Lentivirus | Mouse, permanent | 20 µg | IV, at 48h |
|
- | [134] |
Human umbilical cord MSCs | Density-gradient UC | Akt overexpression | Adenovirus | Rat, permanent | 400 µg | IV, immediate |
|
PDGF-D activation | [135] |
MSCs | ExoQuick-TC (System Biosciences) | miR-150-5p overexpression | Lentivirus | Rat, I/R | 5.8×1012 particles | IM, at 10 min before reperfusion |
|
TXNIP downregulation | [136] |
Rat ADSCs | ExoQuick (System Biosciences) | miR-146a overexpression | Lipofection | Rat, permanent | 400 µg | IV, immediate |
|
EGR1 downregulation | [137] |
Targeting | |||||||||
Human CPCs | UC | CXCR4 | Cell lipofection | Rat, I/R | 2×1011 particles | IV, at 3h after reperfusion |
|
ERK1/2 activation | [138] |
Rat BM-MSCs | UC | cTnI-targeted short peptide | Cell electroporation | Rat, permanent | 200 µg | IV, immediate |
|
- | [139] |
Mouse BM-MSCs | Total Exosome Isolation Reagent (Invitrogen) | Cardiac homing peptide (CSTSMLKAC) |
Lentivirus transfection of cells | Mouse, permanent | 4×109 particles/50 μg | IV, immediate |
|
- | [140] |
HEK293 | Tangential Flow Filtration | Cardiac targeting peptide (APWHLSSQYSRT) |
Cell lipofection | Mouse, no infarct | 150 µg | IV, no infarct | • 15% enhanced heart delivery of EVs | - | [141] |
Rat BM-MSCs | UC | Monocyte membrane | EVs and monocyte membrane fusion | Mouse, I/R | 10 µg | IV, at days 2 and 3 |
|
- | [142] |
CDCs | Ultrafiltration | Cardiac homing peptide (CSTSMLKAC) |
EVs conjugation via a DOPE-NHS linker | Rat, I/R | 6×109 particles | IV, at 24h |
|
- | [143] |
ADSCs: adipose tissue-derived mesenchymal stem cells; BM-MSCs: bone marrow-derived mesenchymal stromal cells; CPCs: cardiac progenitor cells; cTnI: cardiac troponin-I; CXCR4: C-X-C chemokine receptor type 4; DOPE-NHS: dioleoylphosphatidylethanolamine N-hydroxysuccinimide; EGR1: early growth response factor 1; EVs: extracellular vesicles; HEK293T: Human embryonic kidney 293 cell line; I/R: ischemia/reperfusion; IM: intramyocardially; IV: intravenously; lncRNA: long non-coding RNA; MI: myocardial infarction; miRNA: microRNA; MSCs: mesenchymal stromal cells; PDGF-D: platelet-derived growth factor D; SDF1: stromal-derived factor 1; SEC: size-exclusion chromatography; Sfrp2: secreted frizzled-related protein 2; TIMP2: tissue matrix metalloproteinase inhibitor 2; TXNIP: thioredoxin-interacting protein; UC: ultracentrifugation.