UNLABELLED: Invasive plants along transportation corridors can significantly threaten ecosystems and biodiversity if they spread beyond anthropogenic environments. Rapid evolution may increase the ability of invading plant populations to establish in resident plant communities over time, posing a challenge to invasion risk assessment. We tested for adaptive differentiation in Dittrichia graveolens (stinkwort), an invasive species of ruderal habitat in California that is increasingly spreading away from roadsides into more established vegetation. We collected seeds from eight pairs of vegetated sites and their nearest (presumed progenitor) roadside population. We assessed differentiation between populations in roadside and vegetated habitat for germination behavior and for response to competition in a greenhouse experiment. We also tested for increased performance in vegetated habitat with a grassland field experiment including a neighbor removal treatment. Germination rates were slightly reduced in seeds from vegetated sites, which may indicate lower seed viability. Otherwise, plants did not show consistent differences between the two habitat types. Competition strongly reduced performance of D. graveolens in both the greenhouse and in the field, but plants originating from vegetated sites did not show enhanced competitive ability. Our findings show no evidence of adaptive differentiation between D. graveolens populations from roadside and vegetated habitats to date, suggesting that invasiveness in grasslands has not been enhanced by rapid evolution in the 40 + years since this species was introduced to California. Evolutionary constraints or potentially high levels of gene flow at this small scale may limit adaptation to novel habitats along roadsides. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10530-024-03359-6.

BACKGROUND: Stem cell products are increasingly entering early stage clinical trials for treating retinal degeneration. The field is learning from experience about comparability of cells proposed for preclinical and clinical use. Without this, preclinical data supporting translation to a clinical study might not adequately reflect the performance of subsequent clinical-grade cells in patients. METHODS: Research-grade human neural progenitor cells (hNPC) and clinical-grade hNPC (termed CNS10-NPC) were injected into the subretinal space of the Royal College of Surgeons (RCS) rat, a rodent model of retinal degeneration such as retinitis pigmentosa. An investigational new drug (IND)-enabling study with CNS10-NPC was performed in the same rodent model. Finally, surgical methodology for subretinal cell delivery in the clinic was optimized in a large animal model with Yucatan minipigs. RESULTS: Both research-grade hNPC and clinical-grade hNPC can survive and provide functional and morphological protection in a dose-dependent fashion in RCS rats and the optimal cell dose was defined and used in IND-enabling studies. Grafted CNS10-NPC migrated from the injection site without differentiation into retinal cell phenotypes. Additionally, CNS10-NPC showed long-term survival, safety and efficacy in a good laboratory practice (GLP) toxicity and tumorigenicity study, with no observed cell overgrowth even at the maximum deliverable dose. Finally, using a large animal model with the Yucatan minipig, which has an eye size comparable to the human, we optimized the surgical methodology for subretinal cell delivery in the clinic. CONCLUSIONS: These extensive studies supported an approved IND and the translation of CNS10-NPC to an ongoing Phase 1/2a clinical trial (NCT04284293) for the treatment of retinitis pigmentosa.