Young Women Diagnosed With Breast Cancer: Why Is No One Telling Me to Get a Mammogram?

Age-related macular degeneration (AMD) is a progressive, degenerative disease and the most common cause of blindness in developed countries []. Two primary forms of advanced AMD have been identified: neovascular (exudative) and non-neovascular (nonexudative). About 90% of AMD patients have the nonexudative form characterized by drusen formation within the macula []. Late stage nonexudative AMD, referred to as geographic atrophy (GA-AMD), features degeneration of the retinal pigment epithelial (RPE) cells followed by the loss of the light-sensitive photoreceptor cells, leading to central vision loss []. Currently, there are two FDA approved complement inhibitor therapies, pegcetacoplan and avacincaptad pegol, for GA-AMD. However, these complement inhibitors have limited efficacy and undesired side effects; thus alternative therapeutic approaches are needed [,]. Therapeutic development for GA-AMD has included immunomodulation, visual cycle modulation, neuroprotection, and cell-based therapies []. One example, human central nervous system stem cells (HuCNS-SC), grown as neurospheres, have been in clinical development as a neuroprotective agent to slow the progression of GA-AMD for decades []. HuCNS-SC are self-renewing, multilineage-producing cells that hold great promise for treating a large number of neurodegenerative disorders [–]. They were established by isolating CD133 + cells from human fetal brain tissue, which are highly enriched for neurosphere-initiating cells with self-renewal capabilities at the single-cell level. Based on these initial characterizations, individual HuCNS-SC banks have been successfully established by directly isolating HuCNS-SC with high levels of CD133, but little or no CD24 (CD133 + /CD24-/lo) from single donated human fetal brain tissues (16–20 weeks gestation) []. These cells undergo selective propagation in a defined serum-free culture media, are grown as neurospheres, and can be cryopreserved in cell banks []. Previous studies have shown that HuCNS-SC are capable of proliferation, migration, and multilineage differentiation in a site-appropriate manner when transplanted into brains or spinal cord of immunodeficient mice, thereby recapitulating temporal development of HuCNS-SC from the human fetal brain []. These banked cells continue to express HuCNS-SC markers such as CD133 and Sox2. Additionally, they have biological HuCNS-SC activities with multiple mechanisms of actions, providing neuroprotection, myelination, and retinal preservation via site-appropriate global migration [–]. Banked HuCNS-SC have been transplanted into the Royal College of Surgeons (RCS) rat model, a well-established model used to evaluate cellular therapeutics for AMD [–]. Previous studies have shown that HuCNS-SC survived for at least 8 months after transplantation into the subretinal space of P21 RCS rats, where they preserved host photoreceptors from degeneration, and helped minimize long-term vision loss []. The mechanism of action for this benefit was multifactorial, but included the ability of HuCNS-SC cells to phagocytose photoreceptor outer segments and to significantly increase host RPE cell proliferation [,].