Cell-Deposited Matrix Improves Retinal Pigment Epithelium Survival on Aged Submacular Human Bruch's Membrane

Sugino, Ilene K.; Gullapalli, Vamsi K.; Sun, Qian; Wang, Jianqiu; Nunes, Celia F.; Cheewatrakoolpong, Noounanong; Johnson, Adelaide M.; Degner, Benjamin C.; Hua, Jianyuan; Liu, Tong; Chen, Wei; Li, Hong; Zarbin, Marco A.

doi:10.1167/iovs.10-6112

Cited by 33 publications

(30 citation statements)

References 82 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…57 In the present study, we show with TEM, qPCR, IF, and western blotting that the hESC-RPE produce and assemble their own basal lamina on all investigated coatings. Interestingly, marked differences in the thickness of the basal lamina were detected in TEM analysis.…”

Section: Discussionsupporting

confidence: 57%

Structure and Barrier Properties of Human Embryonic Stem Cell–Derived Retinal Pigment Epithelial Cells Are Affected by Extracellular Matrix Protein Coating

Sorkio

Hongisto

Kaarniranta

et al. 2014

Tissue Engineering Part A

View full text Add to dashboard Cite

Extracellular matrix (ECM) interactions play a vital role in cell morphology, migration, proliferation, and differentiation of cells. We investigated the role of ECM proteins on the structure and function of human embryonic stem cell-derived retinal pigment epithelial (hESC-RPE) cells during their differentiation and maturation from hESCs into RPE cells in adherent differentiation cultures on several human ECM proteins found in native human Bruch's membrane, namely, collagen I, collagen IV, laminin, fibronectin, and vitronectin, as well as on commercial substrates of xeno-free CELLstartÔ and MatrigelÔ. Cell pigmentation, expression of RPE-specific proteins, fine structure, as well as the production of basal lamina by hESC-RPE on different protein coatings were evaluated after 140 days of differentiation. The integrity of hESC-RPE epithelium and barrier properties on different coatings were investigated by measuring transepithelial resistance. All coatings supported the differentiation of hESC-RPE cells as demonstrated by early onset of cell pigmentation and further maturation to RPE monolayers after enrichment. Mature RPE phenotype was verified by RPE-specific gene and protein expression, correct epithelial polarization, and phagocytic activity. Significant differences were found in the degree of RPE cell pigmentation and tightness of epithelial barrier between different coatings. Further, the thickness of self-assembled basal lamina and secretion of the key ECM proteins found in the basement membrane of the native RPE varied between hESC-RPE cultured on compared protein coatings. In conclusion, this study shows that the cell culture substrate has a major effect on the structure and basal lamina production during the differentiation and maturation of hESC-RPE potentially influencing the success of cell integrations and survival after cell transplantation.

show abstract

Section: Discussionsupporting

confidence: 57%

Structure and Barrier Properties of Human Embryonic Stem Cell–Derived Retinal Pigment Epithelial Cells Are Affected by Extracellular Matrix Protein Coating

Sorkio

Hongisto

Kaarniranta

et al. 2014

Tissue Engineering Part A

View full text Add to dashboard Cite

show abstract

“…In contrast, resurfacing human aged and AMD Bruch's membrane with BCE-ECM improved RPE survival in organ culture by more than 200% ( fig. 2) [30]. BCE-treated Bruch's membrane explants not only showed significantly higher RPE nuclear density than control explants, the RPE expressed more differentiated features on BCEtreated explants than on untreated explants.…”

Section: Biochemical Restoration Of Aged Human Bruch's Membranementioning

confidence: 92%

“…Using an organ culture model of RPE attachment to human Bruch's membrane, we found that hES-RPE survival on AMD Bruch's membrane is poor [28]. With the addition of exogenous extracellular matrix (ECM) [29] or conditioned medium, however, survival and differentiation can be improved substantially [30].…”

mentioning

confidence: 99%

Biochemical Restoration of Aged Human Bruch's Membrane: Experimental Studies to Improve Retinal Pigment Epithelium Transplant Survival and Differentiation

Sugino

Sun

Cheewatrakoolpong

et al. 2014

Developments in Ophthalmology

Self Cite

View full text Add to dashboard Cite

Suspensions of human embryonic stem cell-derived retinal pigment epithelium (hES-RPE) and human fetal RPE resurface aged and age-related macular degeneration (AMD) Bruch's membrane to a limited degree at day 21 in organ culture. Survival and differentiation of hES-RPE and human fetal RPE on aged or AMD Bruch's membrane are enhanced greatly (200%) if a biologically synthesized extracellular matrix (bovine corneal endothelial cell extracellular matrix) is laid down on Bruch's membrane prior to transplantation. Transplanted RPE survival is enhanced even more (400-1,000%) if Bruch's membrane is treated with bovine corneal endothelial cell-conditioned medium during organ culture of hES-RPE or fetal RPE on aged or AMD Bruch's membrane. Future efforts are focused on identifying the bioactive components of bovine corneal endothelial cell-conditioned medium, so that this material can be reconstituted for clinical use as an adjunct to improve RPE transplant survival and differentiation in AMD eyes.

show abstract

“…Nevertheless, in vitro, the alteration of the extracellular matrix (ECM) composition of Bruch's membrane through the addition of conditioned media helped the attachment of seeded RPE cells to aged Bruch's membrane. 126,[151][152][153] Another approach is to increase the surface levels of integrins. It has been shown that uncultured RPE cells from aged donors fail to adhere, s u r v i v e , o r f u n c t i o n o n B r u c h ' s m e mbrane.…”

Section: Enhancing the Adhesion And Survival Of Transplanted Rpe Cellsmentioning

confidence: 99%

Enhancing RPE Cell-Based Therapy Outcomes for AMD: The Role of Bruch's Membrane

Heller

Martin

2014

Trans. Vis. Sci. Tech.

View full text Add to dashboard Cite

Age-related macular degeneration (AMD) is the leading cause of legal blindness in older people in the developed world. The disease involves damage to the part of the retina responsible for central vision. Degeneration of retinal pigment epithelial (RPE) cells, photoreceptors, and choriocapillaris may contribute to visual loss. Over the past decades, scientists and clinicians have tried to replace lost RPE cells in patients with AMD using cells from different sources. In recent years, advances in generating RPE cells from stem cells have been made and clinical trials are currently evaluating the safety and efficiency of replacing the degenerated RPE cell layer with stem cellderived RPE cells. However, the therapeutic success of transplantation of stem cellderived RPE cells may be limited unless the transplanted cells can adhere and survive in the long term in the diseased eye. One hallmark of AMD is the altered extracellular environment of Bruch's membrane to which the grafted cells have to adhere. Here, we discuss recent approaches to overcome the inhibitory environment of the diseased eye and to enhance the survival rate of transplanted RPE cells. Our aim is to highlight novel approaches that may have the potential to improve the efficacy of RPE transplantation for AMD in the future.

show abstract

Cell-Deposited Matrix Improves Retinal Pigment Epithelium Survival on Aged Submacular Human Bruch's Membrane

Abstract: Increased RPE survival can be achieved on aged submacular human Bruch's membrane by resurfacing the latter with a cell-deposited ECM. Caucasian eyes seem to benefit the most, as cell survival is the worst on submacular Bruch's membrane in these eyes.

Cited by 33 publications

References 82 publications

Structure and Barrier Properties of Human Embryonic Stem Cell–Derived Retinal Pigment Epithelial Cells Are Affected by Extracellular Matrix Protein Coating

Structure and Barrier Properties of Human Embryonic Stem Cell–Derived Retinal Pigment Epithelial Cells Are Affected by Extracellular Matrix Protein Coating

Biochemical Restoration of Aged Human Bruch's Membrane: Experimental Studies to Improve Retinal Pigment Epithelium Transplant Survival and Differentiation

Enhancing RPE Cell-Based Therapy Outcomes for AMD: The Role of Bruch's Membrane

Contact Info

Product

Resources

About