Publications
Here is a selection of publications where different laminin isoforms were used to create more authentic cell culture systems.
Generation of 3D retinal tissue from human pluripotent stem cells using a directed small molecule-based serum-free microwell platform
Hassan Rashidi, Yeh Chwan Leong, Kerrie Venner, Hema Pramod, Qi-Zhen Fei, Owen J. R. Jones, Dale Moulding & Jane C. Sowden Scientific Reports, 2022
Biolaminin 521 (LN521) was used as the matrix in a 2D/3D system for retinal differentiation from human pluripotent stem cells in an agarose micromould platform. To achieve a serum-free and animal-free protocol for producing retinal tissue with photoreceptor cells, the scientists successfully replaced Matrigel (which is derived from mouse tumor cells) with laminin-521, and fetal bovine serum (FBS) with human platelet lysate (HPL). The culture system first allows cells to self-organize forming neuroepithelial structures that resemble embryonic optic vesicles, and then mimics retinogenesis and produces retinal tissue with photoreceptor cells. The generated photoreceptors exhibited key photoreceptor cell features including the formation of OS-like structures containing proteins involved in phototransduction.
Laminin Expression in Adult and Developing Retinae: Evidence of Two Novel CNS Laminins
Libby R.T., Champliaud M-F, Claudepierre T., Xu Y., Gibbons E.P., Koch M., Burgeson R.E., Hunter D.D, Brunken W.J. The Journal of Neuroscience, 2000
Here, they examine the expression of all known laminin chains within the retina. The interphotoreceptor matrix (and, during early development, the subretinal space) contains the laminin a3, a4, a5, b2, b3, g2, and g3 chains. This suggests the presence of three laminins: laminin-332, laminin-423, and laminin-523. These laminin isoforms could exert important effects on photoreceptor development and may play a role in photoreceptor production, stability and synaptic organization.
Long-Term Efficacy of GMP Grade Xeno-Free hESC-Derived RPE Cells Following Transplantation
McGill T.J., Bohana-Kashtan O., Stoddard J.W., Andrews M.D., Pandit N., Rosenberg-Belmaker L.R., Wiser O., Matzrafi L., Banin E., Reubinoff B., Netzer N., Irving C. Trans Vis Sci Tech., 2017
Publication from researchers at Cell Cure Neurosciences where they display the efficacy of RPE cells derived under xeno-free conditions from clinical and xeno-free grade human embryonic stem cells following transplantation into the subretinal space of Royal College of Surgeons (RCS) rats. BioLamina’s laminin cell culture substrate is being used in the differentiation protocol. The results of this study demonstrate that the transplantation of OpRegen into the subretinal space of RCS rats protected the retinal structure, rescued visual function, preserved rod and cone photoreceptors long-term (up to 180 days). Transplanted RPE cells were identified in both the subretinal space and integrated into the host RPE monolayer in animals of all age groups, and often contained internalized photoreceptor outer segments. Optomotor tracking was rescued in a dose-dependent manner. The outer nuclear layer was significantly thicker in cell-treated eyes than controls up to P150. No pathology was observed. This data combined with data collected in definitive safety studies (tumorigenicity and spiking and safety/biodistribution) has resulted in an FDA approved IND and a Phase 1/2a clinical trial for AMD patients is ongoing, NCT02286089.
Xeno-Free and Defined Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells Functionally Integrate in a Large-Eyed Preclinical Model
Plaza Reyes A., Petrus-Reurer S., Antonsson L., Stenfelt S., Bartuma H., Panula S., Mader T., Douagi I., Andre H., Hovatta O., Lanner F., Kvanta A. Stem Cell Reports, 2015
This publication by the groups of Drs. Hovatta, Lanner, and Kvanta describe the production of hESC-RPE cells in a xeno-free and defined manner. In the paper, they describe an effective differentiation methodology using a human recombinant laminin-521 matrix with a xeno-free and defined medium. The differentiated RPE cells exhibit native characteristics including morphology, pigmentation, marker expression, monolayer integrity, polarization, and phagocytic activity. The authors also established a large-eyed geographic atrophy model that allowed in vivo imaging of the hESC-RPE and host retina. Cells were transplanted in suspension and showed long-term integration and formed polarized monolayers exhibiting phagocytic and photoreceptor rescue capacity.