Page 49 - Mesenchymal Stem Cell-Derived Exosomes as an Emerging Paradigm for Regenerative Therapy and Nano-Medicine

Function of exosomes in ocular diseases

angiogenesis, etc. Studies have shown that exosomes play miR-208a in cardiac myofibroblastic differentiation where it
a very important role in the treatment of glaucoma, diabetic plays an important role. Overproduction of angiotensin II is
retinopathy, keratitis, macular degeneration, and other eye a key factor in inducing myocardial fibrosis and even heart
[9]
diseases. failure. Wang et al showed that increased angiotensin II in
Exosomes can promote the repair of injured nerves Some myocardial fibrosis models led to down-regulation of miR-
bioactive substances in exosomes play the role of repairing 425 and miR-744 in cardiomyocyte-derived exosomes. By
nerves by affecting the related signal pathways and the using luciferase assay and immunoblotting, transforming
expression of some proteins. Spinal marrow injury is the most growth factor-β1 (TGF-β1) was identified as a direct target for
serious complication of spinal column injury, characterized miR-425 and miR-744, which induced an increase in collagen
by irreversible damage to nerves and impaired function. I. However, in the CCL4-induced rat liver fibrosis model,
The traditional treatment of spinal marrow injury (including transplantation of spinal mesenchymal stem cell-derived
surgery, drugs, hyperbaric oxygen chamber, etc.) cannot repair exosomes (HBMSCs-Exo) can slow the progression of liver
the damaged nerve, but research has proved that stem cell- fibrosis in rats and reduce inflammation. The mechanism of
[4]
derived exosomes can do this. Ren et al found that after the action is to promote the expression of WISP1 and CyclinD1
exosomes derived from adipose stem cells (ADSCs) were through Wnt/β - Catenin (PPARγ, Wnt3a, Wnt10b, β-Catenin,
modified by miR-133b, they may promote the functional WISP1, CyclinD1) pathway, so as to inhibit the activation of
recovery of injured nerves by affecting the protein signal hepatic stellate cells, reduce the expression of type I collagen,
[11]
[10]
transduction pathways related to neurofilament (NF), glial and reduce liver fibrosis . Xiao et al found that rat bone
fibrillary acidic protein (GFAP), growth associated protein 43 marrow mesenchymal stem cells exosomes (BMSCs-exo)
(GAP43) and myelin basic protein (MBP); Similarly, Yuan can transfer miR-340 to endometrial stromal cells (ESC).
[5]
et al found that the exosomes of mesenchymal stem cell miRNA-340 can inhibit the increase of collagen 1α1 and
(MSC) modified by miR-126 can protect neurons of rats with α-SMA protein caused by TGF-β1, reduce endometrial damage
spinal cord injury, stimulate axon regeneration, and promote and collagen accumulation, and prevent endometrial fibrosis.
the recovery of motor function of hind limbs. Yu et al used The healing process of wounds (cornea, conjunctiva, etc.)
[6]
lasers to cause retinal damage in animals, and then injected needs to undergo epithelial cell proliferation and migration,
mesenchymal stem cell-derived exosomes (MSC-exo) into myofibroblast formation, inflammatory response, and collagen
the vitreous cavity. The results showed that exosomes could deposition. Shojaati et al removed the corneal epithelium
[12]
reduce the infiltration of immune cells such as CD68, inhibit of mice. After the treatment of MSCs from corneal structural
the apoptosis of retinal ganglion cell (RGC) and reduce stem cells exosomes (CSSC-Exo), the expression of wound
the damage of retina by down regulating the expression of fibrosis genes COL3A1 and ACTA2 decreased, neutrophil
monocyte chemotactic protein (MCP)-1. Intravenous injection infiltration decreased, and corneal scarring reduce. Scarring of
of MSC-exo can improve nerve injury, neurite remodeling and cornea can lead to the decrease of vision. At present, corneal
[7]
neovascularization after ischemic brain injury . At present, transplantation is the first choice for patients with large
there is no effective treatment for the irreversible loss of vision area scarring of cornea, so the lack of fresh corneal donors
caused by optic neuropathy, glaucoma and other reasons. becomes the biggest obstacle. Exosomes come from a wide
Perhaps exosomes therapy can effectively solve this problem. range of sources, which can effectively solve the shortage of
Exosomes can inhibit fibrosis The formation of fibrosis is corneal donors and eliminate the rejection caused by corneal
mainly due to the increase of a large number of fibroblasts transplantation.
[13]
and abnormal proliferation of extracellular matrix, resulting Exosomes can modulate immune function Khare et al
in organ dysfunction caused by excessive fibrosis of organs. confirmed that spinal cord MSC-derived exosomes can inhibit
As a cell signaling substance, exosomes contain a variety the proliferation of monocytes, T cells and B cells, especially
of biologically active substances, which can induce fibrosis B lymphocytes. Further, measured by ELISA, the production
of organs by binding to specific target cells under certain of IgM was significantly inhibited, but the production of IgG
conditions. Examples of this are cardiomyocyte fibrosis, liver and IgA did not change significantly. At the present, MSC
[8]
fibrosis and renal fibrosis, etc. In the study by Yang et al , the transplantation has been used to treat a variety of immune-
mechanism of cardiomyocyte-derived exosomes regulating related diseases, such as type I diabetes, graft-versus-host
fibroblast production was emphasized. miRNA-208a isolated disease, bronchopulmonary dysplasia, multiple sclerosis,
[14]
from cardiomyocyte-derived exosomes promotes cardiac Crohn’s disease, etc . Compared with stem cells, exosomes
fibroblast proliferation and myofibroblast differentiation derived from stem cells have stronger immunoregulatory
in vitro, while Dyrk2 acts as a target gene binding site for function. Type 1 diabetes (T1DM), also known as insulin-

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