Purpose: The goal of this study was to develop an immunodeficient rat model of retinal degeneration (RD nude rats) that will not reject transplanted human cells.
Methods: SD-Tg(S334ter)3Lav females homozygous for a mutated mouse rhodopsin transgene were mated with NTac:NIH-Whn (NIH nude) males homozygous for the Foxn1 (rnu) allele. Through selective breeding, a new stock, SD-Foxn1 Tg(S334ter)3Lav (RD nude) was generated such that all animals were homozygous for the Foxn1 (rnu) allele and either homo- or hemizygous for the S334ter transgene. PCR-based assays for both the Foxn1 (rnu) mutation and the S334ter transgene were developed for accurate genotyping. Immunodeficiency was tested by transplanting sheets of hESC-derived neural progenitor cells to the subretinal space of RD nude rats, and, as a control, NIH nude rats. Rats were killed between 8 and 184 days after surgery, and eye sections were analyzed for human, neuronal, and glial markers.
Results: After transplantation to RD nude and to NIH nude rats, hESC-derived neural progenitor cells differentiated to neuronal and glial cells, and migrated extensively from the transplant sheets throughout the host retina. Migration was more extensive in RD nude than in NIH nude rats. Already 8 days after transplantation, donor neuronal processes were found in the host inner plexiform layer. In addition, host glial cells extended processes into the transplants. The host retina showed the same photoreceptor degeneration pattern as in the immunocompetent SD-Tg(S334ter)3Lav rats. Recipients survived well after surgery.
Conclusions: This new rat model is useful for testing the effect of human cell transplantation on the restoration of vision without interference of immunosuppression.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4374984 | PMC |
| http://dx.doi.org/10.1007/s00417-014-2638-y | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Synthetic Studies on Vitamin D Derivatives with Diverse but Selective Biological Activities.
Chem Pharm Bull (Tokyo)
January 2025
Faculty of Pharmaceutical Sciences, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan.
Article Synopsis
- A-ring modifications in 1α,25-dihydroxyvitamin D enhance its binding to the vitamin D receptor (VDR) and increase its stability in cells by resisting metabolism, leading to longer-lasting effects.
- Various modified A-ring precursors synthesized from d-glucose showed specific biological activities with minimal calcemic side effects, including MART-10's potent antitumor effects in cancer models and AH-1's superior bone-forming properties in osteoporosis models compared to natural vitamin D.
- Ongoing research includes developing a library of fluorinated vitamin D analogs with potential anti-inflammatory effects and therapeutic applications for conditions like psoriasis, alongside the creation of the VDR-silent analog KK-052, which selectively inhibits SREBP/SC
Cell-free biodegradable electroactive scaffold for urinary bladder tissue regeneration.
Nat Commun
January 2025
Department of Biomedical Engineering, Northwestern University, Evanston, IL, USA.
Tissue engineering heavily relies on cell-seeded scaffolds to support the complex biological and mechanical requirements of a target organ. However, in addition to safety and efficacy, translation of tissue engineering technology will depend on manufacturability, affordability, and ease of adoption. Therefore, there is a need to develop scalable biomaterial scaffolds with sufficient bioactivity to eliminate the need for exogenous cell seeding.
View Article and Find Full Text PDFOrthotopic meningioma rat model exhibits morphological and immunohistochemical congruency and epigenetic concordance with benign primary patient-derived tumors.
Sci Rep
December 2024
Department of Neurosurgery, Odense University Hospital, J. B. Winsløvs Vej 4, Odense C, 5000, Denmark.
Meningiomas are the most common primary central nervous system tumor. Clinical trials have failed to support effective medical treatments, despite initially promising animal studies. A key issue could be that available experimental models fail to mimic the clinical situation.
View Article and Find Full Text PDFFAM96B negatively regulates FOSL1 to modulate the osteogenic differentiation and regeneration of periodontal ligament stem cells via ferroptosis.
Stem Cell Res Ther
December 2024
Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, 100081, China.
Background: Periodontal ligament stem cell (PDLSC)-based therapy is one of the methods to assist bone regeneration. Understanding the functional regulation of PDLSCs and the mechanisms involved is a crucial issue in bone regeneration. This study aimed to explore the roles of the family with sequence similarity 96 member B (FAM96B) in the functional regulation of PDLSCs.
View Article and Find Full Text PDFOptimizing Drug Delivery to the Brain for Breast Metastasis: A Novel Method for Tumor Targeting.
Cureus
November 2024
Radiology, Wayne State University, Detroit, USA.
Introduction: Brain metastases are difficult to treat due to the blood-brain barrier limiting the delivery of therapeutic agents to the brain effectively. Intraventricular drug delivery has not been well studied for intra-axial pathologies. However, our prior work demonstrated that intraventricular drug delivery in a hyperosmolar vehicle showed preferential accumulation of drug within breast cancer tissue compared to surrounding brain parenchyma.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!