Improving Stem Cell Delivery to the Trabecular Meshwork Using Magnetic Nanoparticles

Snider, Eric J.; Kubelick, Kelsey P.; Tweed, Kelsey; Kim, R. K.; Li, Yaofa; Gao, Kun; Read, A. Thomas; Emelianov, Stanislav; Ethier, C. Ross

doi:10.1038/s41598-018-30834-7

Cited by 39 publications

(43 citation statements)

References 40 publications

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“…Although some ADSCs were attached to the iris and corneal endothelium, they did not induce obvious ocular abnormalities. Using magnetic nanoparticles to improve stem cell homing 46 might be a good option to further increase the efficiency of ADSC homing and integration.…”

Section: Discussionmentioning

confidence: 99%

“…We have successfully induced ADSCs to differentiate into corneal keratocytes, 45 a cell type derived from neural crest, and thus, sharing the same embryonic origin as TM cells. Snider et al 46 reported that adipose‐derived MSCs can be specifically delivered to the TM tissue using magnetic nanoparticles, which suggests the feasibility of using ADSCs for TM regeneration. Here, we demonstrate that ADSCs can be induced to differentiate into TM‐like cells (ADSC‐TM) with characteristics of TM cells, namely gene expression patterns, response to dexamethasone (DEX) stimulation, phagocytic capacity, and ability to maintain aqueous humor dynamics in vivo.…”

Section: Introductionmentioning

confidence: 99%

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Adipose‐derived stem cells integrate into trabecular meshwork with glaucoma treatment potential

et al. 2020

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The trabecular meshwork (TM) is an ocular tissue that maintains intraocular pressure (IOP) within a physiologic range. Glaucoma patients have reduced TM cellularity and, frequently, elevated IOP. To establish a stem cell-based approach to restoring TM function and normalizing IOP, human adipose-derived stem cells (ADSCs) were induced to differentiate to TM cells in vitro. These ADSC-TM cells displayed a TM cell-like genotypic profile, became phagocytic, and responded to dexamethasone stimulation, characteristic of TM cells. After transplantation into naive mouse eyes, ADSCs and ADSC-TM cells integrated into the TM tissue, expressed TM cell markers, and maintained normal IOP, outflow facility, and extracellular matrix. Cell migration and affinity results indicated that the chemokine pair CXCR4/SDF1 may play an important role in ADSC-TM cell homing. Our study demonstrates the possibility of applying autologous or allogeneic ADSCs and ADSC-TM cells as a potential treatment to restore TM structure and function in glaucoma. K E Y W O R D Sadipose stem cells; differentiation, homing, integration, trabecular meshwork | 7161 ZHOU et al.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Adipose‐derived stem cells integrate into trabecular meshwork with glaucoma treatment potential

et al. 2020

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“…Using enucleated tissue CP injuries can only be tracked for a few hours after injury creation. For assessing multi-day or multi-week time courses an alternative approach will be needed where anterior tissue can be maintained long term post-enucleation, such as in organ culture [41][42][43][44][45] , or by transitioning to an animal model. Another limitation is the eye holder housing the eye in gelatin is uniformly shaped and thus does not exactly mimic the complex geometry of the ocular orbit.…”

Section: Discussionmentioning

confidence: 99%

Development and Characterization of a Benchtop Corneal Puncture Injury Model

Snider

Cornell

Acevedo

et al. 2020

Sci Rep

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During recent military operations, eye-related injuries have risen in frequency due to increased use of explosive weaponry which often result in corneal puncture injuries. these have one of the poorest visual outcomes for wounded soldiers, often resulting in blindness due to the large variations in injury shape, size, and severity. As a result, improved therapeutics are needed which can stabilize the injury site and promote wound healing. Unfortunately, current corneal puncture injury models are not capable of producing irregularly shaped, large, high-speed injuries as seen on the battlefield, making relevant therapeutic development challenging. Here, we present a benchtop corneal puncture injury model for use with enucleated eyes that utilizes a high-speed solenoid device suitable for creating militaryrelevant injuries. We first established system baselines and ocular performance metrics, standardizing the different aspects of the benchtop model to ensure consistent results and properly account for tissue variability. The benchtop model was evaluated with corneal puncture injury objects up to 4.2 mm in diameter which generated intraocular pressure levels exceeding 1500 mmHg. Overall, the created benchtop model provides an initial platform for better characterizing corneal puncture injuries as seen in a military relevant clinical setting and a realistic approach for assessing potential therapeutics. Eye-related injuries have risen in recent combat operations due to increased use of explosive weaponry. From World War I to Operations Iraqi and Enduring Freedom, eye-related injuries increased from 2% to 13% of combat injuries, respectively 1. The most prevalent ocular injuries are corneal abrasions, lacerations, and full thickness punctures, resulting in vision impairment without timely intervention 2. While there are treatments readily available for superficial corneal damage, more severe injuries such as full-thickness corneal punctures (CP) are challenging to treat. CP wounds predominantly enter through the cornea and may damage the iris, lens, and even retina, depending on the speed, material, and trajectory of how the eye was punctured 3. These injuries are not mitigated until injured warfighters are evacuated back to an ophthalmic specialist for surgical repair. For CP injuries where intraocular foreign bodies are present, the average time between point of injury and surgical repair was 21 days in recent combat operations 4. An open, untreated CP injury is highly susceptible to infection, metallic poisoning, and reduced intraocular pressure (IOP). Further, low IOP results in poor nutrient delivery throughout the eye, impacting viability and function of ocular tissues 3,5,6. As a result, CP injuries result in poor visual outcomes even after medical intervention 7. To date, when CP injuries occur on the battlefield the chain of treatment first involves placing a rigid eye shield on the injury site until evaluation by an ophthalmic specialist. If no intraocular foreign body (IOFB) is present, sutures are the gold...

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“…Human adipose-derived mesenchymal stem cells (MSCs; Lonza) were labeled with PBNCs using previously reported methods, 4 and minimal impact on stem cell viability and multipotency following labeling was observed through in vitro assessments, which are commonly performed to independently assess nanoparticle impact on cellular function and anticipate effects in vivo . 25 Briefly, at roughly 80% confluence, MSCs were incubated with PBNC-containing media overnight. PBNCs were dispersed in the media at an optical density of 2, corresponding to roughly

of media.…”

Section: Methodsmentioning

confidence: 99%

In vivo photoacoustic guidance of stem cell injection and delivery for regenerative spinal cord therapies

Kubelick

Emelianov

2020

Neurophoton.

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Significance: Stem cell therapies are of interest for treating a variety of neurodegenerative diseases and injuries of the spinal cord. However, the lack of techniques for longitudinal monitoring of stem cell therapy progression is inhibiting clinical translation. Aim: The goal of this study is to demonstrate an intraoperative imaging approach to guide stem cell injection to the spinal cord in vivo. Results may ultimately support the development of an imaging tool that spans intra-or postoperative environments to guide therapy throughout treatment. Approach: Stem cells were labeled with Prussian blue nanocubes (PBNCs) to facilitate combined ultrasound and photoacoustic (US/PA) imaging to visualize stem cell injection and delivery to the spinal cord in vivo. US/PA results were confirmed by magnetic resonance imaging (MRI) and histology. Results: Real-time intraoperative US/PA image-guided injection of PBNC-labeled stem cells and three-dimensional volumetric images of injection provided feedback necessary for successful delivery of therapeutics into the spinal cord. Postoperative MRI confirmed delivery of PBNClabeled stem cells. Conclusions: The nanoparticle-augmented US/PA approach successfully detected injection and delivery of stem cells into the spinal cord, confirmed by MRI. Our work demonstrated in vivo feasibility, which is a critical step toward the development of a US/PA/MRI platform to monitor regenerative spinal cord therapies.

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Improving Stem Cell Delivery to the Trabecular Meshwork Using Magnetic Nanoparticles

Cited by 39 publications

References 40 publications

Adipose‐derived stem cells integrate into trabecular meshwork with glaucoma treatment potential

Adipose‐derived stem cells integrate into trabecular meshwork with glaucoma treatment potential

Development and Characterization of a Benchtop Corneal Puncture Injury Model

In vivo photoacoustic guidance of stem cell injection and delivery for regenerative spinal cord therapies

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