Cell Therapy Using Extraocular Mesenchymal Stem Cells

Nieto-Miguel, Teresa; Galindo, Sara; López‐Paniagua, Marina; Pérez, Isidro A.; Herreras, J.M.; Calonge, Margarita

doi:10.1007/978-3-030-01304-2_17

Cited by 3 publications

(5 citation statements)

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“…Whether MSC can transdifferentiate into CE cells is still uncertain. On the other hand, the capacity of MSC in secreting trophic and growth factors, small RNAs via extracellular vesicles or exosomes, could exert anti-inflammatory and immunomodulatory effects and to stimulate resident viable cells to survive and proliferate, hence reducing tissue injury [10, 17]. In addition, the secretome of ADSC can suppress epithelial-mesenchymal transition (EMT) of diseased CE, in attenuating fibrosis and restoring the corneal transparency [53].…”

Section: Discussionmentioning

confidence: 99%

“…Patients usually require a prolonged course of systemic immunosuppression, which could cause adverse effects, including hyperglycemia, elevated creatinine, and hypertension, as well as elevated intraocular pressure and cataract [7, 8]. Adult tissue-specific MSC (mesenchymal stem cells) have been introduced as an accessible and non-immunogenic stem cell source, with potential therapeutic value in CE regeneration and treatment of PED for corneal surface disorders [9, 10]. These multipotent cells have the capacity to differentiate towards adipocyte, chondrocyte, and osteoblasts [11, 12].…”

Section: Introductionmentioning

confidence: 99%

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Cellular therapy of corneal epithelial defect by adipose mesenchymal stem cell-derived epithelial progenitors

et al. 2020

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BackgroundPersistent epithelial defects (PED), associated with limbal stem cell deficiency (LSCD), require ocular surface reconstruction with a stable corneal epithelium (CE). This study investigated CE reformation using human adipose mesenchymal stem cells (ADSC), which derived epithelial progenitors via mesenchymal-epithelial transition (MET).MethodsSTEMPRO human ADSC were cultured with specific inhibitors antagonizing glycogen synthase kinase-3 and transforming growth factor-β signaling, followed by culture under a defined progenitor cell targeted-epithelial differentiation condition to generate epithelial-like cells (MET-Epi), which were characterized for cell viability, mesenchymal, and epithelial phenotypes using immunofluorescence and flow cytometry. Tissue-engineered (TE) MET-Epi cells on fibrin gel were transplanted to corneal surface of the rat LSCD model caused by alkali injury. Epithelial healing, corneal edema, and haze grading, CE formation were assessed by fluorescein staining, slit lamp bio-microscopy, anterior segment optical coherence tomography, and immunohistochemistry.ResultsCD73high/CD90high/CD105high/CD166high/CD14negative/CD31negative human ADSC underwent MET, giving viable epithelial-like progenitors expressing δNp63, CDH1 (E-cadherin), epidermal growth factor receptor, integrin-β4, and cytokeratin (CK)-5, 9. Under defined epithelial differentiation culture, these progenitors generated MET-Epi cells expressing cell junction proteins ZO1 and occludin. When transplanted onto rat corneal surface with LSCD-induced PED, TE-MET-Epi achieved more efficient epithelial healing, suppressed corneal edema, and opacities, when compared to corneas without treatment or transplanted with TE-ADSC. CE markers (CK3, 12, and CDH1) were expressed on TE-MET-Epi-transplanted corneas but not in other control groups.ConclusionHuman ADSC-derived epithelial-like cells, via MET, recovered the CE from PED associated with LSCD. ADSC can be a viable adult stem cell source for potential autologous epithelial cell-based therapy for corneal surface disorders.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cellular therapy of corneal epithelial defect by adipose mesenchymal stem cell-derived epithelial progenitors

et al. 2020

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“…As recently documented, MSCs were the most commonly used stem cell type for cellular and tissue-engineering therapies in Europe between 2016 and 2017 [ 39 ]. This is mainly due to the capacity of MSCs to produce growth factors, to modulate immune and inflammatory properties, and to differentiate into multiple cell lineages depending on the environmental signals [ 60 ]. MSCs secrete epithelial growth factor, which increases corneal epithelial cell proliferation [ 61 , 62 ].…”

Section: The Present: Available Stem Cell-based Therapiesmentioning

confidence: 99%

Goals and Challenges of Stem Cell-Based Therapy for Corneal Blindness Due to Limbal Deficiency

et al. 2021

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Corneal failure is a highly prevalent cause of blindness. One special cause of corneal failure occurs due to malfunction or destruction of the limbal stem cell niche, upon which the superficial cornea depends for homeostatic maintenance and wound healing. Failure of the limbal niche is referred to as limbal stem cell deficiency. As the corneal epithelial stem cell niche is easily accessible, limbal stem cell-based therapy and regenerative medicine applied to the ocular surface are among the most highly advanced forms of this novel approach to disease therapy. However, the challenges are still great, including the development of cell-based products and understanding how they work in the patient’s eye. Advances are being made at the molecular, cellular, and tissue levels to alter disease processes and to reduce or eliminate blindness. Efforts must be coordinated from the most basic research to the most clinically oriented projects so that cell-based therapies can become an integrated part of the therapeutic armamentarium to fight corneal blindness. We undoubtedly are progressing along the right path because cell-based therapy for eye diseases is one of the most successful examples of global regenerative medicine.

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“…All dexosome concentration after isolation was measured approximately as 1.4 × 10 9 particles/mL for each cryotube of dExOI, dExOII, and dExOIII. Nanoparticle tracking analyses were performed at 1 4 dilution of ExoFreePBS for dExOI, dExOII, dExOIII, and control ExoFreePBS. While naïve particles were 99 nm; dExOI, dExOII, and dExOIII were 134, 142, and 148 nm mean diameter in size, respectively.…”

Section: Nta Analysismentioning

confidence: 99%

“…Exosomes are natural nanoparticles and have some outstanding features; such as being approximately 40–100 nm in size, and they are composed of different types of varied levels of adhesive proteins and amphiphilic lipid molecules in their structure after the production from various types of cells [ 1 ]. Especially, IDc dexosomes have versatile cellular components, such as cell penetration peptides and antigens that can direct the delivery of their cargo (siRNA, miRNA, snRNA, or snoRNA) via both vertical and horizontal transfer [ 2 , 3 ].…”

Section: Introductionmentioning

confidence: 99%

Efficient Doxorubicin Loading to Isolated Dexosomes of Immature JAWSII Cells: Formulated and Characterized as the Bionanomaterial

et al. 2020

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Immature dendritic cells (IDc), ‘dexosomes’, are promising natural nanomaterials for cancer diagnose and therapy. Dexosomes were isolated purely from small-scale-up production by using t25-cell-culture flasks. Total RNA was measured as 1.43 ± 0.33 ng/106 cell. Despite the fact that they possessed a surface that is highly abundant in protein, this did not become a significant effect on the DOX loading amount. Ultrasonication was used for doxorubicin (DOX) loading into the IDc dexosomes. In accordance with the literature, three candidate DOX formulations were designed as IC50 values; dExoIII, 1.8 µg/mL, dExoII, 1.2 µg/mL, and dExoI, 0.6 µg/mL, respectively. Formulations were evaluated by MTT test against highly metastatic A549 (CCL-185; ATTC) cell line. Confocal images of unloaded (naïve) were obtained by CellMaskTM membrane staining before DOX loading. Although, dexosome membranes were highly durable subsequent to ultrasonication, it was observed that dexosomes could not be stable above 70 °C during the SEM-image analyses. dExoIII displayed sustained release profile. It was found that dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA) results were in good agreement with each other. Zeta potentials of loaded dexosomes have approximately between −15 to −20 mV; and, their sizes are 150 nm even after ultrasonication. IDcJAWSII dexosomes can be able to be utilized as the “BioNanoMaterial” after DOX loading via ultrasonication technique.

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Cell Therapy Using Extraocular Mesenchymal Stem Cells

Cited by 3 publications

References 152 publications

Cellular therapy of corneal epithelial defect by adipose mesenchymal stem cell-derived epithelial progenitors

Cellular therapy of corneal epithelial defect by adipose mesenchymal stem cell-derived epithelial progenitors

Goals and Challenges of Stem Cell-Based Therapy for Corneal Blindness Due to Limbal Deficiency

Efficient Doxorubicin Loading to Isolated Dexosomes of Immature JAWSII Cells: Formulated and Characterized as the Bionanomaterial

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