Laminins (LNs) play a central role in the self-assembly and maintenance of basement membranes and are involved in critical interactions between cells and other extracellular matrix (ECM) proteins. Among the defined, xeno-free ECM culture matrices, LNs—namely LN521—have emerged as promising coating systems for the large-scale expansion of induced pluripotent stem cells (iPSCs). The biologic activity of LNs is enhanced by their acidification-induced self-polymerization into a cell-associated network called polylaminin (polyLN), which can recapitulate the native-like polymeric array in a cell-free system. Here, we show for the first time to our knowledge that polyLN521 displays a native-like hexagonal-like structure and that, at basal and low concentrations, it permits the large-scale expansion of human iPSCs. Human iPSCs expanded with polyLN521 maintained the pluripotent state and showed no impairment of karyotype stability or telomere length. These results suggest that low-concentration polyLN521 is a stable and cost-effective coating for large-scale iPSC expansion.

Study design: Investigator-initiated, single-arm, first-in-human pilot study. Objectives: To evaluate the safety and feasibility of intramedullary administration of polymerized laminin in individuals with acute complete spinal cord injury (SCI). Setting: Public and private hospitals in Brazil. Methods: Eight patients with acute traumatic SCI classified as AIS A (C4–T12) were enrolled within days after injury (mean 2.3 days). Polymerized laminin was administered as a single intramedullary dose (1 µg/kg; total 55–80 µg). Patients were followed for 12 months using standardized neurological, laboratory, and neurophysiological assessments. Results: Intramedullary administration was uneventful in all cases. No neurological deterioration or serious adverse events attributable to the intervention were observed. Mild laboratory abnormalities were transient and not associated with hepatic or renal toxicity. Three participants died during follow-up. Deaths were reviewed by the Brazilian National Research Ethics Commission (CONEP) and an external clinical consultant, and were not considered related to the intervention. Neurological improvement of at least two AIS grades was observed in six participants, including one who died after progressing to AIS C. Improvements in motor and/or somatosensory evoked potentials were observed in three patients. Conclusions: Intramedullary administration of polymerized laminin was uneventful and appeared to be safe in this small and heterogeneous cohort. Although the study design does not allow conclusions regarding efficacy, it provides proof-of-concept for this therapeutic approach and justifies further evaluation in controlled clinical studies. The study was initiated in December 2016, prior to current requirements for prospective trial registration.

Angiogenesis is essential not only during embryogenesis but also in adult physiology and disease, relying on vascular endothelial growth factor (VEGF) gradients to guide tip cell sprouting. Cellular prion protein (PrP ^C ), expressed in several neurovascular unit (NVU) cell types, regulates neuronal and astrocytic differentiation through laminin binding, yet its role in angiogenesis remains understudied. Here, we investigated its function in retinal vascular development. In PrP ^C knockout mice, the superficial retinal plexus exhibited increased tip cell density and branching, accompanied by microglial morphofunctional alterations and reduced Vegf-c expression, features consistent with impaired vascular stability. Conditioned media from PrP ^C knockout microglia was sufficient to increase endothelial instability in vitro, indicating that altered microglial signalling can modulate vascular phenotype. Moreover, Laminin 411 / 511 isoforms and Collagen IV showed decreased expression in the retinal vascular basement membrane, supporting altered basement membrane composition. At later developmental stages, absence of PrP ^C led to increased vertical sprouting into deeper retinal layers, resulting in transient hypervascularization of the deep plexus and defective laminin deposition across all vascular layers. These changes were accompanied by altered ZO-1 distribution and disrupted retinal layer organization, as indicated by reduced inter-plexus distance. Collectively, our findings identify PrP ^C as regulator of sprouting angiogenesis and vascular stabilization in the developing retina. The data support a model in which PrP ^C modulates neurovascular interactions, through both microglia-dependent and endothelial-intrinsic mechanisms, although the relative contribution of these components remains to be determined.