Skip to main content
. 2021 Feb 25;11(3):570. doi: 10.3390/nano11030570

Table 3.

Representative preclinical efficacy studies from the last five years using bioengineered extracellular vesicles as a novel class of drug delivery systems for myocardial infarction.

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
  • Decreased apoptosis and fibrosis

  • Induced cardiomyocyte proliferation

  • Increased vascularization

  • Improved cardiac function

- [125]
HEK293T UC miR-21 overexpression - Mouse, permanent 20 µg IM, immediate
  • Inhibited cell apoptosis

  • Increased angiogenesis

  • Reduced scar thickness

  • Improved cardiac function

PDCD4 [126]
Rat BM-MSCs Exosome
Isolation Reagent (RiboBio)
miR-338 overexpression Lipofection Rat, permanent - IM, immediate
  • Improved cardiac function

  • Inhibited cardiomyocyte apoptosis

MAP3K2/JNK pathway [127]
Rat BM-MSCs Exosomes isolation kit (Thermo Fisher Scientific) miR-301 overexpression Lipofection Rat, permanent - IM, at 30 min
  • Inhibited myocardial autophagy

  • Decreased infarct area

  • Improved cardiac function

- [128]
Human umbilical cord MSCs UC miR-181a overexpression Lentivirus Mouse, I/R 200 µg IM, at reperfusion
  • Improved cardiac function

  • Reduced infarct area

  • Reduced inflammation

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
  • Increased number of anti-inflammatory macrophages

  • Decreased infarct size and fibrosis

  • Improved cardiac function

- [130]
Rat ADSCs ExoQuick-TC (System Biosciences) miR-126 overexpression Lipofection Rat, permanent 400 µg IV, immediate
  • Decreased infarct area and fibrosis

  • Reduced inflammation

  • Increased vasculogenesis

- [103]
Human umbilical cord MSCs UC SDF1 overexpression Lipofection Mouse, permanent - IM, immediate
  • Decreased infarct size

  • Reduced tissue damage

  • Reduced levels of inflammatory cytokines

- [131]
Human umbilical cord MSCs UC TIMP2 overexpression Lentivirus Rat, permanent 50 µg/ml IM, immediate
  • Improved cardiac function

  • Decreased infarct size and fibrosis

  • Reduced ventricular dilation

  • Reduced cell apoptosis

  • Increased angiogenesis

  • Inhibited cardiac fibroblast proliferation

Akt/Sfrp2 Pathway [132]
Human MSCs Exosome isolation kit (Invitrogen) LncRNA KLF3-AS1 overexpression Lipofection Rat, permanent 40 µg IV, at 1 week
  • Reduced infarct area

  • Ameliorated apoptosis

  • Decreased inflammation

miR-138-5p and Sirt1 [133]
Mouse BM-MSCs ExoQuick TC (SBI) GATA4 overexpression Lentivirus Mouse, permanent 20 µg IV, at 48h
  • Increased cardiac function

  • Angiogenesis

  • Increased number of c-kit+ cells

  • Decreased apoptotic cardiomyocytes

- [134]
Human umbilical cord MSCs Density-gradient UC Akt overexpression Adenovirus Rat, permanent 400 µg IV, immediate
  • Improved cardiac function

  • Decreased cell apoptosis

  • Enhanced vasculogenesis

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
  • Improved cardiac function

  • Suppressed myocardial remodeling

  • Reduced cardiomyocyte apoptosis

TXNIP downregulation [136]
Rat ADSCs ExoQuick (System Biosciences) miR-146a overexpression Lipofection Rat, permanent 400 µg IV, immediate
  • Reduced apoptosis

  • Inhibited inflammation response

  • Decreased fibrosis and infarct volume

EGR1 downregulation [137]
Targeting
Human CPCs UC CXCR4 Cell lipofection Rat, I/R 2×1011 particles IV, at 3h after reperfusion
  • Increased blood vessel density

  • Reduced infarct size

  • Improved cardiac function

ERK1/2 activation [138]
Rat BM-MSCs UC cTnI-targeted short peptide Cell electroporation Rat, permanent 200 µg IV, immediate
  • Cardiomyocyte proliferation

  • Reduced adverse remodeling

  • Restored cardiac function

- [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
  • Attenuated inflammation

  • Reduced cell apoptosis

  • Increased vasculogenesis

  • Reduced fibrosis

  • Improved cardiac function

- [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
  • Enhanced specific cardiac delivery

  • Angiogenesis

  • Endothelial maturation

  • Anti-inflammatory macrophage modulation

  • Reduced fibrosis

  • Improved cardiac function

- [142]
CDCs Ultrafiltration Cardiac homing peptide
(CSTSMLKAC)
EVs conjugation via a DOPE-NHS linker Rat, I/R 6×109 particles IV, at 24h
  • Increased cell proliferation

  • Angiogenesis

  • Improved heart function

  • Reduced infarct size and fibrosis

- [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.