Transplantation Frontiers

Gullapalli, Vamsi K.; Khodair, Mohamad A.; Wang, Hao; Sugino, Ilene K.; Madreperla, Steven A.; Zarbin, Marco A.

doi:10.1016/b978-1-4557-0737-9.00125-9

Cited by 4 publications

(2 citation statements)

References 331 publications

(379 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Even though the ocular microenvironment is known to be immune privileged ( 13 ), neovascularization associated with LSCD, previous treatments and surgery itself often destroy the immune privilege increasing the susceptibility of the graft to strong alloimmune response and rejection ( 14 , 15 ). Despite some concerns of allo-CLET regarding immunosuppression, rejection, culture techniques and others; one of the clear advantages of allo-CLET is the amount of initial tissue for cultivation that can be used and its quality, aspects that has been described to influence transplantation success ( 9 ).…”

Section: Introductionmentioning

confidence: 99%

Genetic Modification of Limbal Stem Cells to Decrease Allogeneic Immune Responses

Valdivia¹,

Bertolin

Breda

et al. 2021

Front. Immunol.

View full text Add to dashboard Cite

Limbal stem cell (LSC) transplantation is the only efficient treatment for patients affected by LSC deficiency (LSCD). Allogeneic LSC transplantation is one of the most successful alternative for patients with bilateral LSCD. Nevertheless, the high variability of the human leukocyte antigens (HLA) remains a relevant obstacle to long-term allogeneic graft survival. This study characterized the immunologic properties of LSCs and proposed a genetic engineering strategy to reduce the immunogenicity of LSCs and of their derivatives. Hence, LSC HLA expression was silenced using lentiviral vectors encoding for short hairpin (sh) RNAs targeting β2-microglobulin (β2M) or class II major histocompatibility complex transactivator (CIITA) to silence HLA class I and II respectively. Beside the constitutive expression of HLA class I, LSCs showed the capability to upregulate HLA class II expression under inflammatory conditions. Furthermore, LSCs demonstrated the capability to induce T-cell mediated immune responses. LSCs phenotypical and functional characteristics are not disturbed after genetic modification. However, HLA silenced LSC showed to prevent T cell activation, proliferation and cytotoxicity in comparison to fully HLA-expressing LSCs. Additionally; HLA-silenced LSCs were protected against antibody-mediated cellular-dependent cytotoxicity. Our data is a proof-of-concept of the feasibility to generate low immunogenic human LSCs without affecting their typical features. The use of low immunogenic LSCs may support for long-term survival of LSCs and their derivatives after allogeneic transplantation.

show abstract

Section: Introductionmentioning

confidence: 99%

Genetic Modification of Limbal Stem Cells to Decrease Allogeneic Immune Responses

Valdivia¹,

Bertolin

Breda

et al. 2021

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…Third, older RPE may not have the ability to perform all the functions necessary to maintain the photoreceptors [15]. Fetal human RPE attach well to aged human Bruch's membrane, but their long-term survival may not be good on this surface [16]; they are subject to immune rejection [17], and they exhibit morphologic abnormalities after five to six passages, which severely limits their utility as a 'universal' donor source [18].…”

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