Publications by authors named "Natasha Frank"
Purpose: Timely access to clinical genetics consultations remains a barrier to timely genomic medicine services, which new service delivery models might help address.
Methods: We implemented a genetics electronic consultation (eConsult) service staffed by a primary care physician (PCP) champion, supervised by genetics specialists. Chart reviews from July 2018 to January 2022 examined categories of questions received, e-consultant's recommendations, and outcomes of any conventional genetics referrals.
Article Synopsis
- Corneal transparency and avascularity are crucial for clear vision, with a transition to vascularized conjunctiva at the limbus.
- This study identifies a specific sub-population of limbal stromal cells expressing ABCB5, which exhibit mesenchymal stem cell traits and show potential for pluripotency and multi-lineage differentiation.
- ABCB5+ cells demonstrate lower levels of pro-inflammatory and pro-angiogenic factors, suggesting they could help reduce inflammation and neovascularization in the cornea, with potential implications for therapeutic applications elsewhere in the body.
Article Synopsis
- Recessive dystrophic epidermolysis bullosa (RDEB) is a serious skin condition caused by mutations in the COL7A1 gene, leading to severe skin fragility and a high risk of aggressive skin cancer (squamous cell carcinoma).
- This study used whole-genome and RNA sequencing in a single RDEB patient to understand how their skin cancer develops and to look for new treatment options.
- Researchers identified PLK-1 as a potential target for therapy and noted that factors like microsatellite instability and accelerated aging might increase the aggressiveness and early occurrence of the skin cancer associated with RDEB.
Article Synopsis
- * The document outlines a specific method for isolating these BCAM-positive cells from human corneas using techniques like flow cytometry and cell sorting.
- * It provides a step-by-step guide for processing the cells, including dissection, staining, and culturing, to investigate how these cells contribute to corneal regeneration.
Article Synopsis
- The limbus, the area connecting the cornea and conjunctiva, may protect against abnormal blood vessel growth in the cornea, but how it does this isn't fully understood.
- Researchers studied ABCB5, a marker for limbal epithelial stem cells (LESCs), to explore its role in corneal blood vessel development and found it has different effects in young and adult mice.
- The study revealed that ABCB5+ cells can inhibit blood vessel growth during development but promote it during inflammation in adults, suggesting a complex role that could be important for therapies aimed at preventing blindness.
Article Synopsis
- Recessive dystrophic epidermolysis bullosa (RDEB) is a rare and severe skin disorder that causes extreme skin fragility, and a recent clinical trial involving 16 patients showed promising results from treatment with ABCB5 MSCs, which helped reduce disease symptoms.
- A post-hoc analysis assessed the impact of this treatment on overall wound healing, revealing that after 12 weeks, 64.9% of baseline wounds had closed, with a significant reduction in new wounds by 79.3%.
- The findings indicate that ABCB5 MSCs may effectively enhance wound healing and prevent recurrence in RDEB, suggesting a need for future research to evaluate overall wound dynamics rather than just focusing on specific target wounds
Article Synopsis
- Epigenetic modification of DNA through 5-hydroxymethylcytosine (5hmC), produced by TET enzymes, plays a crucial role in regulating gene expression in various tissues, including the cornea of the human eye.
- The study showed that 5hmC and the enzyme TET2 are highly expressed in mature corneal cells, and reducing TET2 led to decreased 5hmC levels and disrupted key molecular pathways that are essential for corneal differentiation.
- These findings suggest that TET2 has a significant role in regulating gene expression in corneal epithelial cells and may offer new strategies for treating corneal diseases linked to issues with cell maturation.
Article Synopsis
- ABCB5 identifies a specific type of skin-resident mesenchymal stem cells (MSCs) that are effective in immune response and wound healing, and can be obtained from discarded skin samples.
- These MSCs have shown promise in treating difficult skin and non-skin inflammatory diseases, supported by preclinical studies and clinical trials.
- Recently, ABCB5 MSCs have gained significant attention, with FDA approval for a pivotal trial in treating recessive dystrophic epidermolysis bullosa and access for chronic venous ulcers in Germany.
Article Synopsis
- Diabetic foot ulcers (DFUs) often resist standard treatments, leading to severe health risks; ABCB5 mesenchymal stem cells (MSCs) could serve as a promising new option due to their healing and anti-inflammatory properties.* -
- The study investigated the angiogenic capabilities of ABCB5 MSCs, showing that they can express factors necessary for blood vessel formation and enhance healing in animal models with ischemia.* -
- A clinical trial demonstrated the safety and effectiveness of applying ABCB5 MSCs to hard-to-treat DFUs, potentially offering a new treatment avenue for those suffering from chronic wounds.*
Article Synopsis
- The research identifies a specific limbal epithelial progenitor subpopulation that is highly proliferative and marked by the expression of basal cell adhesion molecule (BCAM), crucial for corneal epithelial regeneration.
- BCAM-positive cells exist alongside both ABCB5-positive limbal stem cells and ABCB5-negative epithelial cells, indicating a broader role in the corneal epithelium.
- The study reveals that BCAM is essential for cellular migration and differentiation, with its expression regulated by the transcription factor p63, highlighting BCAM's importance in corneal epithelial differentiation.
Article Synopsis
- Many chronic venous ulcers (CVUs) do not heal with standard care, but skin-derived ABCB5 mesenchymal stem cells (MSCs) show promise in improving healing by reducing inflammation.
- A phase I/IIa clinical trial tested these MSCs in patients resistant to typical treatment, where most adverse effects were mild and did not lead to long-term problems.
- The treatment led to a significant reduction in ulcer size after 12 weeks, indicating ABCB5 MSCs could be a valuable addition to therapies for tough-to-heal CVUs, warranting further larger studies.
Article Synopsis
- Severe angiopathy contributes to complications in diabetes, but understanding the mechanisms for effective therapies is lacking.
- Injecting ABCB5 stromal precursors into diabetic wounds in mice significantly speeds up healing by boosting blood vessel formation through the release of angiogenin.
- Blocking angiogenin in these precursors slows healing, highlighting its crucial role in tissue repair for diabetic conditions, paving the way for better treatments for nonhealing wounds.
Article Synopsis
- - RDEB is a severe genetic skin disease caused by a lack of type VII collagen, with no effective treatments available, but ABCB5+ mesenchymal stem cells show promise in helping with symptoms and extending life in affected mouse models.
- - An international clinical trial involving 16 patients tested the safety and effectiveness of ABCB5+ MSCs, with significant reductions in disease activity and itching and pain after treatment, especially noticeable at the 12-week mark.
- - The study indicated that ABCB5+ MSCs have good tolerability and manageable side effects, suggesting they could be a viable therapy for RDEB, warranting further research and development.
Purpose: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). While the ocular surface is considered one of the major SARS-CoV2 transmission routes, the specific cellular tropism of SARS-CoV2 is not fully understood. In the current study, we evaluated the expression and regulation of two SARS-CoV2 viral entry proteins, TMPRSS2 and ACE2, in human ocular epithelial cells and stem cells.
View Article and Find Full Text PDFArticle Synopsis
- Human induced pluripotent stem cells (hiPSCs) can create various organoids, but their potential to contain specific stem cells was unclear until now.
- Researchers discovered a subset of cells in hiPSC-derived corneal epithelial cell sheets that express ABCB5, a marker for corneal epithelial stem cells, indicating these cells can form new tissue.
- These findings suggest that hiPSC-derived cell sheets enriched with ABCB5 could be used for vision recovery in people with stem cell deficiencies, marking a significant step in stem cell research and therapy.
Article Synopsis
- The study focuses on treating severe limbal stem cell deficiency (LSCD) by using a new marker, ABCB5, which helps identify and enrich limbal stem cells (LSCs) for transplantation, improving therapeutic outcomes.
- Researchers developed a standardized production process to create advanced-therapy medicinal products (ATMPs) from ABCB5 LSCs derived from human cadaveric limbal tissue, ensuring high-quality cell expansion and isolation.
- Preclinical trials showed that these ABCB5 LSCs could safely engraft without causing toxicity or tumors, leading to approval by regulatory agencies for a clinical trial to further assess their safety and effectiveness in treating LSCD.
Article Synopsis
- The cancer stem cell (CSC) concept highlights that tumors contain a minority of primitive cells (CSCs) that can drive tumor growth and therapeutic resistance, contrasting with more differentiated cancer cells that cannot sustain the tumor alone.
- The presence of CSCs in colorectal cancer (CRC) has been confirmed through various studies, including human-to-mouse transplantation and lineage-tracing in mice, with established markers for their identification.
- New technologies like single-cell omics are being utilized to better understand CSCs, potentially leading to the discovery of new treatment targets and strategies for CRC treatment.
Article Synopsis
- Recessive dystrophic epidermolysis bullosa (RDEB) is a rare skin disease caused by mutations in type VII collagen, leading to painful blisters and wounds.
- Recent studies suggest that mesenchymal stem cells (MSCs), particularly those from skin (ABCB5+ DSCs), might be more effective at healing RDEB than traditional MSCs from bone marrow (BM-MSCs).
- The research indicates that ABCB5+ DSCs have a better ability to migrate to damaged skin and promote healing through unique genetic traits, pointing towards promising new strategies for regenerative medicine.
Activating transcription factor 3 (ATF-3), a cyclic AMP-dependent transcription factor, has been shown to play a regulatory role in melanoma, although its function during tumor progression remains unclear. Here, we demonstrate that ATF-3 exhibits tumor suppressive function in melanoma. Specifically, ATF-3 nuclear expression was significantly diminished with melanoma progression from nevi to primary to metastatic patient melanomas, correlating low expression with poor prognosis.
View Article and Find Full Text PDFEx vivo-expanded highly pure ABCB5 mesenchymal stromal cells as Good Manufacturing Practice-compliant autologous advanced therapy medicinal product for clinical use: process validation and first in-human data.
Cytotherapy
February 2021
Article Synopsis
- Mesenchymal stromal cells (MSCs) are being explored for treating tissue damage, but their varying properties may explain inconsistent results in therapy; a specific MSC subset identified by the ABCB5 transporter has shown potential for improved outcomes.
- The researchers developed a compliant process to isolate and produce ABCB5 MSCs from skin, leading to a product approved for clinical trials aimed at treating chronic venous ulcers.
- Early results from treating nine patients show a significant median reduction in wound size (63%) after 12 weeks, suggesting that ABCB5 MSCs might provide an effective solution for challenging chronic wounds.
Glioblastoma multiforme (GBM) is a malignant brain tumor with a poor prognosis resulting from tumor resistance to anticancer therapy and a high recurrence rate. Compelling evidence suggests that this is driven by subpopulations of cancer stem cells (CSCs) with tumor-initiating potential. ABC subfamily B member 5 (ABCB5) has been identified as a molecular marker for distinct subsets of chemoresistant tumor-initiating cell populations in diverse human malignancies.
View Article and Find Full Text PDFEpigenetic regulation has a profound influence on stem cell fate during normal development in maintenance of physiologic tissue homeostasis. Here we report diminished ten-eleven translocation (TET) methylcytosine dioxygenase expression and loss of the DNA hydroxymethylation mark 5-hydroxymethylcytosine (5-hmC) in keratinocyte stem cells and transit amplifying cells in human psoriasis and in imiquimod-induced murine psoriasis. Loss of 5-hmC was associated with dysregulated keratinocyte stem cell kinetics, resulting in accumulation of nestin and FABP5-expressing transit amplifying cells to produce classic psoriatic epidermal architecture.
View Article and Find Full Text PDFPurpose: To identify factors associated with isolation yields of ATP-binding cassette (ABC) superfamily member B5 (ABCB5)-positive limbal stem cells (LSCs) from human cadaveric donor eyes.
Methods: Whole eye globes were obtained from the Saving Sight eye bank, Kansas City, MO and the CorneaGen eye bank, Seattle, WA. ABCB5-positive LSCs were sorted by flow cytometry upon anti-ABCB5 monoclonal antibody staining within one week after donor death.
Objective: To identify the genetic cause of disease in a form of congenital spinal muscular atrophy and arthrogryposis (CSMAA).
Methods: A 2-year-old boy was diagnosed with arthrogryposis multiplex congenita, severe skeletal abnormalities, torticollis, vocal cord paralysis, and diminished lower limb movement. Whole-exome sequencing (WES) was performed on the proband and family members.