Safety and feasibility of mesenchymal stem cell therapy in patients with aqueous deficient dry eye disease

Møller-Hansen, Michael; Larsen, Ann‐Cathrine; Toft, Peter Bjerre; Lynggaard, Charlotte Duch; Schwartz, Camilla; Bruunsgaard, Helle; Haack‐Sørensen, Mandana; Ekblond, Annette; Kastrup, Jens; Heegaard, Steffen

doi:10.1016/j.jtos.2020.11.013

Cited by 43 publications

(31 citation statements)

References 30 publications

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“… 95 Likewise, early studies have reported acceptable clinical safety following local administration in patients with severe dry eye disease and acute chemical injuries. 96 , 97 …”

Section: Therapies For Lscdmentioning

confidence: 99%

Current and Emerging Therapies for Limbal Stem Cell Deficiency

Elhusseiny

Soleimani

Eleiwa

et al. 2022

Stem Cells Translational Medicine

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The corneal epithelium serves to protect the underlying cornea from the external environment and is essential for corneal transparency and optimal visual function. Regeneration of this epithelium is dependent on a population of stem cells residing in the basal layer of the limbus, the junction between the cornea and the sclera. The limbus provides the limbal epithelial stem cells (LESCs) with an optimal microenvironment, the limbal niche, which strictly regulates their proliferation and differentiation. Disturbances to the LESCs and/or their niche can lead to the pathologic condition known as limbal stem cell deficiency (LSCD) whereby the corneal epithelium is not generated effectively. This has deleterious effects on the corneal and visual function, due to impaired healing and secondary corneal opacification. In this concise review, we summarize the characteristics of LESCs and their niche, and present the current and future perspectives in the management of LSCD with an emphasis on restoring the function of the limbal niche.

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“… 95 Likewise, early studies have reported acceptable clinical safety following local administration in patients with severe dry eye disease and acute chemical injuries. 96 , 97 …”

Section: Therapies For Lscdmentioning

confidence: 99%

Current and Emerging Therapies for Limbal Stem Cell Deficiency

Elhusseiny

Soleimani

Eleiwa

et al. 2022

Stem Cells Translational Medicine

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“…Four of them propose using ADSC-based therapy to treat the damaged corneal epithelium of patients affected by different pathologies: DED associated with Sjögren’s syndrome (NCT04615455), aqueous-deficient DED (NCT03878628), keratopathy associated with bilateral LSCD (NTC01808378), and corneal ulcer/inflammatory dystrophy (NCT04484402). However, thus far, only one of these clinical trials has been published [ 83 ] ( Table 2 ), reporting new and hopeful results about the safety and efficacy of ADSC-based therapy. Here, researchers reported an open-label, prospective, and phase I clinical trial in which a total of 7 patients affected by aqueous-deficient DED due to Sjögren’s syndrome were treated with a single dose of allogeneic ADSC (an average of 3.10 × 10 6 ADSC/dose), administered directly into the lacrimal gland through transconjunctival injection.…”

Section: Corneal Epithelium Adsc Regeneration: Preclinical and Clinic...mentioning

confidence: 99%

“…Patients were evaluated at 1, 4, and 16 weeks. Adverse events were registered at each visit, although none were related to cell-based therapy [ 83 ]. Symptoms (Ocular Surface Disease Index -OSDI) and signs (osmolarity, tear film breakup time -TBUT, Schirmer’s test, and tendency in corneal staining) improved [ 83 ].…”

Section: Corneal Epithelium Adsc Regeneration: Preclinical and Clinic...mentioning

confidence: 99%

“…Adverse events were registered at each visit, although none were related to cell-based therapy [ 83 ]. Symptoms (Ocular Surface Disease Index -OSDI) and signs (osmolarity, tear film breakup time -TBUT, Schirmer’s test, and tendency in corneal staining) improved [ 83 ]. The authors concluded that a single dose of ADSC injected into the lacrimal glands of patients affected by aqueous-deficient DED can improve their clinical signs and symptoms without adverse events.…”

Section: Corneal Epithelium Adsc Regeneration: Preclinical and Clinic...mentioning

confidence: 99%

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Corneal Regeneration Using Adipose-Derived Mesenchymal Stem Cells

Barrio

Mata

Miguel

et al. 2022

Cells

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Adipose-derived stem cells are a subtype of mesenchymal stem cell that offers the important advantage of being easily obtained (in an autologous manner) from low invasive procedures, rendering a high number of multipotent stem cells with the potential to differentiate into several cellular lineages, to show immunomodulatory properties, and to promote tissue regeneration by a paracrine action through the secretion of extracellular vesicles containing trophic factors. This secretome is currently being investigated as a potential source for a cell-free based regenerative therapy for human tissues, which would significantly reduce the involved costs, risks and law regulations, allowing for a broader application in real clinical practice. In the current article, we will review the existing preclinical and human clinical evidence regarding the use of such adipose-derived mesenchymal stem cells for the regeneration of the three main layers of the human cornea: the epithelium (derived from the surface ectoderm), the stroma (derived from the neural crest mesenchyme), and the endothelium (derived from the neural crest cells).

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“… 26 Most recently, a clinical study has reported the safety of transconjunctival injection of MSCs into the lacrimal gland. 27 Currently, there are insufficient data on the long-term in vivo safety of MSCs administered locally to the eye by subconjunctival injection. Therefore in this study, in preparation for a phase I human clinical trial, we evaluated MSCs in meeting quality control measures including viability and potency, as well as in vivo safety and efficacy in preclinical models.…”

Section: Introductionmentioning

confidence: 99%

Preclinical Evaluation of the Safety and Efficacy of Cryopreserved Bone Marrow Mesenchymal Stromal Cells for Corneal Repair

Putra

Shen

Anwar

et al. 2021

Trans. Vis. Sci. Tech.

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Purpose Mesenchymal stromal cells (MSCs) have been shown to enhance tissue repair as a cell-based therapy. In preparation for a phase I clinical study, we evaluated the safety, dosing, and efficacy of bone marrow–derived MSCs after subconjunctival injection in preclinical animal models of mice, rats, and rabbits. Methods Human bone marrow–derived MSCs were expanded to passage 4 and cryopreserved. Viability of MSCs after thawing and injection through small-gauge needles was evaluated by vital dye staining. The in vivo safety of human and rabbit MSCs was studied by subconjunctivally injecting MSCs in rabbits with follow-up to 90 days. The potency of MSCs on accelerating wound healing was evaluated in vitro using a scratch assay and in vivo using 2-mm corneal epithelial debridement wounds in mice. Human MSCs were tracked after subconjunctival injection in rat and rabbit eyes. Results The viability of MSCs after thawing and immediate injection through 27- and 30-gauge needles was 93.1% ± 2.1% and 94.9% ± 1.3%, respectively. Rabbit eyes demonstrated mild self-limiting conjunctival inflammation at the site of injection with human but not rabbit MSCs. In scratch assay, the mean wound healing area was 93.5% ± 12.1% in epithelial cells co-cultured with MSCs compared with 40.8% ± 23.1% in controls. At 24 hours after wounding, all MSC-injected murine eyes had 100% corneal wound closure compared with 79.9% ± 5.5% in controls. Human MSCs were detectable in the subconjunctival area and peripheral cornea at 14 days after injection. Conclusions Subconjunctival administration of MSCs is safe and effective in promoting corneal epithelial wound healing in animal models. Translational Relevance These results provide preclinical data to support a phase I clinical study.

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Safety and feasibility of mesenchymal stem cell therapy in patients with aqueous deficient dry eye disease

Cited by 43 publications

References 30 publications

Current and Emerging Therapies for Limbal Stem Cell Deficiency

Current and Emerging Therapies for Limbal Stem Cell Deficiency

Corneal Regeneration Using Adipose-Derived Mesenchymal Stem Cells

Preclinical Evaluation of the Safety and Efficacy of Cryopreserved Bone Marrow Mesenchymal Stromal Cells for Corneal Repair

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