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. 2020 Feb 27;9(2):235–248. doi: 10.1007/s40123-020-00239-9

Table 1.

Results of animal studies of the application of UCB therapy to ocular diseases

Study (year) Design Condition Population (n) Treatment Control arm Route Frequency Results
Zhu (2011) [10] Prospective comparative randomized Traumatic optic neuropathy Mice (48) hUCB-MSCs Injured-only group, neurotrophic factor-treated group, and group treated with neurotrophic factor plus hUCB-MSCs Intravitreal Single injection Significant improvement in fVEP testing in treated groups compared with nontreated group. hUCB and neurotrophic factor mixture achieved the best results
Zhao (2011) [17] Prospective comparative randomized ON injury Mice (135) hUCB-MSCs Sham surgery group and unmanipulated mice receiving physiological saline solution Intravitreal Single injection Increased RGC density, increased BDNF and GDNF mRNA expression, and improvement in pathological retinal changes in the hUCB-MSCs-treated groups
Chen (2013) [16] Prospective comparative randomized ON injury Mice (132) hUCB-MSCs Phosphate-buffered saline Intravitreal Single injection Decreased RGC apoptosis and increased RGC survival in the early phase following treatment. Beneficial effect declined over time
Jiang (2013) [15] Prospective comparative randomized Traumatic optic neuropathy Mice (195) hUCB-MSCs Sham treatment Intravitreal Single injection Ameliorated fVEP testing; increased RGC count and decreased RGC apoptosis
Zhang (2015) [12] Prospective comparative randomized ON injury Rabbit (48) hUCB-MSCs Sham treatment Intravitreal Single injection Decreased ultrastructural ON damage; improved biomechanical properties (increased maximum load, maximum stress, maximum strain, elastic limit load, elastic limit stress, and elastic limit strain) of ON
Shao (2015) [14] Prospective comparative Corneal endothelium deficiency Rabbit (16) hUCB-EPCs labeled with CD34 immunomagnetic nanoparticles CD34 immunomagnetic nanoparticle-labeled UCB EPCS without a magnet; EDM stripping without injection of cells; unmanipulated rabbits Intracameral injection plus magnetic attraction (cells migrate directionally) Single injection Treated corneas became relatively transparent, with little edema
Lv (2016) [13] Prospective comparative randomized ON injury Rabbit (60) hUCB-MSCs Intravitreal BDNF 1 × 106 hUCB-MSCs intravitreally Single injection Recovery of viscoelasticity of ON (increased stress relaxation and creep properties) in treated groups
Chung (2016) [8] Prospective comparative ON crush Mice (90) hUCB-MSCs Sham treatment Intraarterial Single injection Increased axon survival rates, increased visual function (GAP-43 upregulation), and increased oxygen availability (HIF-1α upregulation)
Wang (2016) [24] Prospective comparative randomized Oxygen-induced retinopathy Mice (7) hUCB-MSCs Unmanipulated mice; phosphate-buffered saline-treated group. Intravitreal Single injection Faster recovery from retinopathy and lower number of neovascular nuclei in UCB-MSCs-treated group
Zhang (2017) [9] Prospective comparative randomized Diabetic retinopathy Mice (–) hUCB-MSCs Sham treatment Intravitreal 0.2 × 106 cells in 2 μL Single injection Attenuation of retinal vascular dysfunction, BDNF and Thy-1 upregulation; decreased retinal vessel leakage, better visual function based on positive ERG testing
Mohamed (2017) [22] Prospective comparative Cryo-induced retinal injury Mice (48) hUCB-MSCs Unmanipulated mice; intravenously treated group Intravitreal vs intravenous injection Single injection Near-normal retinal structure in MSCs-treated group. Modulation of oxidant-apoptotic status: increased expression of Bcl-2, HMOX1, TXN2; downregulation of 3-NT and caspase-3. Increased bFGF
Dong (2017) [23] Prospective comparative randomized Diabetic retinopathy Mice (60) hUCB-MSCs 2 μL phosphate-buffered saline Intravitreal 2 μL Single injection Ameliorated retinal layer structure; reduced retinal vessel leakage
Reid (2017) [20] Prospective interventional comparative Oxygen-induced retinopathy Mice (–) hUCB-MSCs Unmanipulated mice Intravitreal vs intraarterial Single injection Comparable beneficial effects of intravitreal and intravascular administration routes on vascular repair. Fewer human cells observed in the retinal vasculature following systemic delivery
He (2018) [21] Prospective comparative Retinal laser injury Mice (–) hUCB-MSCs Sham treatment

Intravitreal 5 μL PBS alone, MSCs-Exos at a concentration of 50 μg/mL, and

different concentrations of exosomes (Exo-L: 25 μg/mL, Exo-M: 50 μg/mL, and Exo-H: 75 μg/mL) for 8, 16, and 24 h

Single injection Downregulated expression of VEGF mRNA in RPE cells induced by MSC-derived exosomes in vivo and ex vivo after blue light stimulation; subsequent CNV reduction and ameliorated visual function
Jì (2018) [25] Prospective comparative randomized Ocular hypertension Mice (54) hUCB-MSCs Unmanipulated mice; phosphate-buffered saline-treated group Intravitreal Single injection Increased numbers of RGCs and axons and increased expression of GDNF and BDNF in hUCB-MSCs-treated groups
Koh (2018) [19] Prospective interventional comparative Retinal degeneration Mice (–) hUCB-MSCs plus steroids and cyclosporine A Unmanipulated mice Subretinal Single or double injection Preserved retinal synaptic connectivity and decreased Müller glial cell reactivity
Huang (2019) [11] Prospective comparative ON crush Mice (/) hUCB- 2D-MSCs vs hUCB- 3D-MSCs ON exposed without crush Intravitreal injection Single injection 2D-MSCs had stronger promoting effect than 3D-MSCs on RGC survival and ON axonal regeneration. Improved fVEP and sustained secretion of regeneration-stimulating factors (SCGF-β, HGF, MCP-1, IL-8, and SDF-1α). 2D-MSCs induced the activation of key neuroprotection pathways (JAK/STAT3 and MAPK/ERK)

UCB umbilical cord blood, ON optic nerve, hUCB human umbilical cord blood, MSCs mesenchymal stem cells, RGCs retinal ganglion cells, fVEP flash visual evoked potential, SCGF-β stem cell growth factor-β, HGF hepatocyte growth factor, MCP-1 monocyte chemoattractant protein-1, SDF-1α stromal cell-derived factor, VEGF vascular endothelial growth factor, RPE retinal pigment epithelial, CNV corneal neovascularization, BDNF brain-derived neurotrophic factor, ERG electroretinogram recording, Bcl-2 B cell lymphoma (Bcl)-2 gene, HMOX heme oxygenase, TXN thioredoxin, 3-NT 3-nitrotyrosine, bFGF basic fibroblast growth factor, GAP-43 growth-associated protein-43, HIF-1α hypoxia-inducible factor-1α, hUCB-EPCs human umbilical cord blood endothelial progenitor cells, EDDM endothelium-Descemet membrane layer, GDNF glial cell line-derived neurotrophic factor