Mesenchymal Stem Cell–Derived Small Extracellular Vesicles Promote Neuroprotection in Rodent Models of Glaucoma

Mead, Ben; Amaral, Juan; Tomarev, Stanislav I.

doi:10.1167/iovs.17-22855

Cited by 110 publications

(123 citation statements)

References 52 publications

Supporting

Mentioning

108

Contrasting

Order By: Relevance

“…Stem cell‐based therapies can greatly impact the field of regenerative medicine. MSCs have been used in preclinical and clinical studies to treat degenerative diseases, such as AD (Cui et al, ; Han et al, ; J. Shin et al, ; X. Wang, Ma, et al, ), DDD (Ahn et al, ; Beeravolu et al, ; Pereira et al, ; Perez‐Cruet et al, ), MS (Harris et al, ; Nasri et al, ; Planchon et al, ), PD (Jamali et al, ; H. Kim, Lee, et al, ), and RDD (Mead, Amaral, & Tomarev, ), as summarized in Table . The regenerative mechanisms of transplanted MSCs for these diseases are still unclear; however, some reports have suggested that MSCs have the potential to differentiate or have paracrine effects in vivo (Lee, Choi, Cha, & Hwang, ).…”

Section: Promising Applications Of Mscsmentioning

confidence: 99%

See 1 more Smart Citation

Mesenchymal stem cells: Cell therapy and regeneration potential

Brown

McKee

Bakshi

et al. 2019

J Tissue Eng Regen Med

427

310

View full text Add to dashboard Cite

Rapid advances in the isolation of multipotent progenitor cells, routinely called mesenchymal stromal/stem cells (MSCs), from various human tissues and organs have provided impetus to the field of cell therapy and regenerative medicine. The most widely studied sources of MSCs include bone marrow, adipose, muscle, peripheral blood, umbilical cord, placenta, fetal tissue, and amniotic fluid. According to the standard definition of MSCs, these clonal cells adhere to plastic, express cluster of differentiation (CD) markers such as CD73, CD90, and CD105 markers, and can differentiate into adipogenic, chondrogenic, and osteogenic lineages in vitro. However, isolated MSCs have been reported to vary in their potency and self‐renewal potential. As a result, the MSCs used for clinical applications often lead to variable or even conflicting results. The lack of uniform characterization methods both in vitro and in vivo also contributes to this confusion. Therefore, the name “MSCs” itself has been increasingly questioned lately. As the use of MSCs is expanding rapidly, there is an increasing need to understand the potential sources and specific potencies of MSCs. This review discusses and compares the characteristics of MSCs and suggests that the variations in their distinctive features are dependent on the source and method of isolation as well as epigenetic changes during maintenance and growth. We also discuss the potential opportunities and challenges of MSC research with the hope to stimulate their use for therapeutic and regenerative medicine.

show abstract

Section: Promising Applications Of Mscsmentioning

confidence: 99%

“…Wang, Ma, et al, 2018), DDD (Ahn et al, 2015;Beeravolu et al, 2018;Pereira et al, 2016;Perez-Cruet et al, 2018), MS (Harris et al, 2018;Nasri et al, 2018;Planchon et al, 2018), PD (Jamali et al, 2018;H. Kim, Lee, et al, 2018), and RDD (Mead, Amaral, & Tomarev, 2018), as summarized in Table 2.…”

Section: Promising Applications Of Mscsmentioning

confidence: 99%

Mesenchymal stem cells: Cell therapy and regeneration potential

Brown

McKee

Bakshi

et al. 2019

J Tissue Eng Regen Med

427

310

View full text Add to dashboard Cite

show abstract

“…Exosomes were characterized via Western blot by their positive staining for the exosome markers Syntenin 1 and CD63 and negative staining for high/lowdensity lipoprotein markers ApoA1 and ApoB. 24 Briefly, exosomes were lysed in passive lysis buffer (Promega, Madison, WI, USA; #E1531) and protein samples (20 μg) were separated on 4% to 12% Bis-Tris protein gels at 150 V for 40 minutes. After transfer to polyvinylidene fluoride membranes and blocking in 10% Western blot blocking buffer (Roche, Basel, Switzerland) in Tris-buffered saline (TBS), proteins were stained overnight in primary antibody (Table) diluted in TBS.…”

Section: Exosome Isolationmentioning

confidence: 99%

“…Densitometry of Western blot bands was analyzed using ImageJ software (National Institutes of Health, Bethesda, MD, USA) as previously reported. 24 All exosomes samples used in the study comprised exosomes pooled from three MSC donors.…”

Section: Exosome Isolationmentioning

confidence: 99%

“…14 Our most recent work has demonstrated that MSCderived exosomes exert a significant neuroprotective effect on RGCs. 23,24 Exosomes are small extracellular vesicles that contain microRNA, mRNA, proteins, and lipids. There is still contention in the field on the appropriate terminology, whether they should be called exosomes or extracellular vesicles, with exosomes reserved for those preparations that have used extensive isolation and characterization steps.…”

mentioning

confidence: 99%

See 1 more Smart Citation

TNFα-Mediated Priming of Mesenchymal Stem Cells Enhances Their Neuroprotective Effect on Retinal Ganglion Cells

Mead

Chamling

Zack

et al. 2020

Invest. Ophthalmol. Vis. Sci.

Self Cite

View full text Add to dashboard Cite

Citation: Mead B, Chamling X, Zack DJ, Ahmed Z, Tomarev S. TNFα-mediated priming of mesenchymal stem cells enhances their neuroprotective effect on retinal ganglion cells. Invest Ophthalmol Vis Sci. 2020;61(2):6. https://doi.org/10.1167/iovs.61.2.6 PURPOSE.To determine whether priming of bone marrow mesenchymal stem cells (MSCs) by signals from injured retina, particularly tumor necrosis factor α (TNFα), increase their exosomes' neuroprotective efficacy on retinal ganglion cells (RGCs). METHODS.MSCs were primed with retinal cell culture conditioned medium, with or without the TNFα blocker etanercept or TNFα prior to isolation of exosomes. MSC conditioned medium or exosomes were added to rat retinal cultures or human stem cell-derived retinal ganglion cell (hRGC) cultures, and RGC neuroprotective effects were quantified. Luminex assays were used to compare primed versus unprimed exosomes. RESULTS.MSC conditioned medium and exosomes exerted a significant neuroprotective effect on injured rat and hRGC. This effect was significantly increased after MSCs were primed with retinal conditioned medium or TNFα. Blocking of TNFα signaling with etanercept prevented priming-induced RGC neuroprotective efficacy. Priming increased Pigment epithelium-derived factor (PEDF) and VEGF-AA exosomal abundance.CONCLUSIONS. MSC exosomes promote RGC survival not just in rodent retinal cultures but also with hRGC. Their efficacy can be further enhanced through TNFα priming with the mechanism of action potentially mediated, at least in part, through increased levels of PEDF and VEGF-AA.

show abstract

Circulating Small Extracellular Vesicles Involved in Systemic Regulation Respond to RGC Degeneration in Glaucoma

Li,

Zhang,

Wang

et al. 2024

Advanced Science

View full text Add to dashboard Cite

Glaucoma is a leading cause of irreversible blindness worldwide and is characterized by progressive retinal ganglion cell (RGC) degeneration and vision loss. Since irreversible neurodegeneration occurs before diagnosable, early diagnosis and effective neuroprotection are critical for glaucoma management. Small extracellular vesicles (sEVs) are demonstrated to be potential novel biomarkers and therapeutics for a variety of diseases. In this study, it is found that intravitreal injection of circulating plasma‐derived sEVs (PDEV) from glaucoma patients ameliorated retinal degeneration in chronic ocular hypertension (COH) mice. Moreover, it is found that PDEV‐miR‐29s are significantly upregulated in glaucoma patients and are associated with visual field defects in progressed glaucoma. Subsequently, in vivo and in vitro experiments are conducted to investigate the possible function of miR‐29s in RGC pathophysiology. It is showed that the overexpression of miR‐29b‐3p effectively prevents RGC degeneration in COH mice and promotes the neuronal differentiation of human induced pluripotent stem cells (hiPSCs). Interestingly, engineered sEVs with sufficient miR‐29b‐3p delivery exhibit more effective RGC protection and neuronal differentiation efficiency. Thus, elevated PDEV‐miR‐29s may imply systemic regulation to prevent RGC degeneration in glaucoma patients. This study provides new insights into PDEV‐based glaucoma diagnosis and therapeutic strategies for neurodegenerative diseases.

show abstract

Mesenchymal Stem Cell–Derived Small Extracellular Vesicles Promote Neuroprotection in Rodent Models of Glaucoma

Cited by 110 publications

References 52 publications

Mesenchymal stem cells: Cell therapy and regeneration potential

Mesenchymal stem cells: Cell therapy and regeneration potential

TNFα-Mediated Priming of Mesenchymal Stem Cells Enhances Their Neuroprotective Effect on Retinal Ganglion Cells

Circulating Small Extracellular Vesicles Involved in Systemic Regulation Respond to RGC Degeneration in Glaucoma

Contact Info

Product

Resources

About