Epiretinal Membrane Formation After Intravitreal Autologous Stem Cell Implantation in a Retinitis Pigmentosa Patient

Kim, Ju Young; You, Yong Sung; Kim, Soon Hyun; Kwon, Oh Woong

doi:10.1097/icb.0000000000000327

Cited by 32 publications

(26 citation statements)

References 18 publications

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“…Detailed reports of the results of these trials are pending, but several serious adverse effects associated with BMSC therapy from unregulated clinical studies have been reported recently. They include retinal detachment, severe macular pucker, and retinal artery occlusion following subretinal, intravitreal and periocular injections of BMSCs (Boudreault et al, 2016; Kim et al, 2016; Leung et al, 2016). Some of these adverse effects mirror reactive retinal gliosis, fibrovascular proliferation and vascular obstruction observed in preclinical studies using intravitreal and intravascular mesenchymal stem cells (Ge et al 2014; Tassoni et al, 2015; Figure 3).…”

Section: Clinical Trialsmentioning

confidence: 99%

Advances in bone marrow stem cell therapy for retinal dysfunction

Park

Moisseiev

Bauer

et al. 2017

Progress in Retinal and Eye Research

103

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The most common cause of untreatable vision loss is dysfunction of the retina. Conditions, such as age-related macular degeneration, diabetic retinopathy and glaucoma remain leading causes of untreatable blindness worldwide. Various stem cell approaches are being explored for treatment of retinal regeneration. The rationale for using bone marrow stem cells to treat retinal dysfunction is based on preclinical evidence showing that bone marrow stem cells can rescue degenerating and ischemic retina. These stem cells have primarily paracrine trophic effects although some cells can directly incorporate into damaged tissue. Since the paracrine trophic effects can have regenerative effects on multiple cells in the retina, the use of this cell therapy is not limited to a particular retinal condition. Autologous bone marrow-derived stem cells are being explored in early clinical trials as therapy for various retinal conditions. These bone marrow stem cells include mesenchymal stem cells, mononuclear cells and CD34+ cells. Autologous therapy requires no systemic immunosuppression or donor matching. Intravitreal delivery of CD34+ cells and mononuclear cells appears to be tolerated and is being explored since some of these cells can home into the damaged retina after intravitreal administration. The safety of intravitreal delivery of mesenchymal stem cells has not been well established. This review provides an update of the current evidence in support of the use of bone marrow stem cells as treatment for retinal dysfunction. The potential limitations and complications of using certain forms of bone marrow stem cells as therapy are discussed. Future directions of research include methods to optimize the therapeutic potential of these stem cells, non-cellular alternatives using extracellular vesicles, and in vivo high-resolution retinal imaging to detect cellular changes in the retina following cell therapy.

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Section: Clinical Trialsmentioning

confidence: 99%

Advances in bone marrow stem cell therapy for retinal dysfunction

Park

Moisseiev

Bauer

et al. 2017

Progress in Retinal and Eye Research

103

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“…These complications are sometimes associated with the surgery. However, more studies showed that intravitreal transplantation of other kinds of stem cells also resulted in ERM formation [18][19][20], which suggest that not only surgery process but also transplantation sites may affect therapeutic outcomes. When stem cells are used to treat RDD, cells can be transplanted into the subretinal space or the vitreous chamber.…”

Section: Introductionmentioning

confidence: 99%

“…ERM attaches to the retina and contracts and distorts the retina [26]. Previous studies have shown that ERM formed in patients received intravitreal transplantation of bone marrow-derived stem cells and ASCs [17,19]. However, the ERM formation process, ERM cellular components, and the contribution of stem cells to ERM formation in these patients are not clear.…”

Section: Introductionmentioning

confidence: 99%

Transplantation Site Affects the Outcomes of Adipose-Derived Stem Cell-Based Therapy for Retinal Degeneration

Wei

et al. 2020

Stem Cells International

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Adipose-derived stem cells (ASCs) have shown a strong protective effect on retinal degenerative diseases (RDD) after being transplanted into the subretinal space in an animal model. Recently, several clinical trials have been conducted to treat RDD with intravitreal transplantation of stem cells, including ASCs. However, the outcomes of the clinical trials were not satisfactory. To investigate if the transplantation site alters the outcome of stem cell-based therapy for RDD, we isolated rat ASCs (rASCs) and labeled them with green fluorescent protein. Autologous rASCs were grafted into the vitreous chamber or subretinal space in a rat RDD model induced by sodium iodate (SI). The electric response was recorded by ERG. The anatomic structure of the retina was observed in cryosections of rat eyes at posttransplantation weeks 1, 2, and 4. Neural retina apoptosis and epiretinal membrane-(ERM-) like structure formation were investigated by immunostaining. The intravitreal transplantation of rASCs resulted in an extinguished electric response, although the rosette formation and apoptosis of neural retina were reduced. However, the rASCs that grafted in the subretinal space protected the retina from the damage caused by SI, including a partial recovering of the electric response and a reduction in rosette formation. Intravitreally grafted rASCs formed a membrane, resulting in retina folding at the injection site. Müller cells, retinal pigment epithelial cells, and microglial cells migrated from the retina to the rASC-formed membrane and subsequently formed an ERM-like structure. Furthermore, vitreous fluid promoted rASC migration, and rASC-conditioned medium enhanced Müller cell migration as indicated by in vitro studies. These data suggested that the vitreous chamber is not a good transplantation site for ASC-based therapy for RDD and that a deliberate decision should be made before transplantation of stem cells into the vitreous chamber to treat RDD in clinical trials.

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“…36 There have been similar recent reports of proinflammatory vitreous clumping 37 of MSCs injected intravitreally as well as thick epiretinal membrane formation following MSC administration in humans. 38 These adverse effects may also be due in part to the inconsistency in MSC isolation and preparation. An attempt to standardise the identification of these cells led to the development of the International Society for Cellular Therapy criteria, 39 but problems continue to be reported despite this and may limit the degree to which MSCs can successfully be used to confer neuroprotection to retinal ganglion cells.…”

Section: Cell Therapymentioning

confidence: 99%

Neuroprotection in Glaucoma: Towards Clinical Trials and Precision Medicine

Khatib

Martin

2019

Current Eye Research

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Purpose: The eye is currently at the forefront of translational medicine and therapeutics. However, despite advances in technology, primary open-angle glaucoma remains the leading cause of irreversible blindness worldwide. Traditional intraocular pressure (IOP)-lowering therapies are often not sufficient to prevent progression to blindness, even in patients with access to high-quality healthcare. Neuroprotection strategies, which aim to boost the ability of target cells to withstand a pathological insult, have shown significant promise in animal models but none have shown clinically relevant efficacy in human clinical trials to date. We sought to evaluate the current status of neuroprotection clinical trials for glaucoma and identify limitations which have prevented translation of new glaucoma therapies to date. Methods: Literature searches identified English language references. Sources included MEDLINE, EMBASE, the Cochrane Library and Web of Science databases; reference lists of retrieved studies; and internet pages of relevant organisations, meetings and conference proceedings, and clinical trial registries. Results: We discuss six key neuroprotective strategies for glaucoma that have reached the clinical trial stage. Delivery of neurotrophic factors through gene therapy is also progressing towards glaucoma clinical trials. Refinements in trial design and the use of new modalities to define structural and functional endpoints may improve our assessment of disease activity and treatment efficacy. Advances in our understanding of compartmentalised glaucomatous degeneration and continued progress in the molecular profiling of glaucoma patients will enable us to predict individual risk and tailor treatment. Conclusion: New approaches to future glaucoma neuroprotection trials could improve the prospects for new glaucoma therapies. Glaucoma treatment tailored according to an individual's unique risk profile may become increasingly common in the future. ARTICLE HISTORY

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Epiretinal Membrane Formation After Intravitreal Autologous Stem Cell Implantation in a Retinitis Pigmentosa Patient

Abstract: This is the first report of ERM formation following intravitreal autologous stem cells injection. CD34-positive stem cells were detected in a human eye at 4 months after injection. Further studies are needed to determine how stem cells caused ERM and how long they would stay in the eye.

Cited by 32 publications

References 18 publications

Advances in bone marrow stem cell therapy for retinal dysfunction

Advances in bone marrow stem cell therapy for retinal dysfunction

Transplantation Site Affects the Outcomes of Adipose-Derived Stem Cell-Based Therapy for Retinal Degeneration

Neuroprotection in Glaucoma: Towards Clinical Trials and Precision Medicine

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