A5063668393- Pluripotent Stem Cells Research
- Animal Genetics and Reproduction
- Reproductive Biology and Fertility
- Virus-based gene therapy research
- CRISPR and Genetic Engineering
- Acute Myeloid Leukemia Research
- Renal and related cancers
- Hematopoietic Stem Cell Transplantation
- Immune cells in cancer
- Epigenetics and DNA Methylation
- RNA Interference and Gene Delivery
- Immune Cell Function and Interaction
- CAR-T cell therapy research
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Tissue Engineering and Regenerative Medicine
- Cancer Research and Treatments
- Cancer Genomics and Diagnostics
- Neuroinflammation and Neurodegeneration Mechanisms
- T-cell and B-cell Immunology
- Xenotransplantation and immune response
- Immune responses and vaccinations
- Mesenchymal stem cell research
- Reproductive System and Pregnancy
- Eosinophilic Disorders and Syndromes
- Asthma and respiratory diseases
National Heart Lung and Blood Institute
2016-2025
National Institutes of Health
2016-2025
Seoul National University
2006-2012
Induced pluripotent stem cell (iPSC)-based therapies have great potential for regenerative medicine but are also potentially associated with tumorigenic risks. Current rodent models not optimal predictors of efficiency and safety clinical application. Therefore, we developed a clinically relevant nonhuman primate model to assess the in vivo efficacy both undifferentiated differentiated iPSCs autologous settings without immunosuppression. Undifferentiated indeed form mature teratomas...
Hematopoietic stem cell (HSC) gene therapy has curative potential; however, its use is limited by the morbidity and mortality associated with current chemotherapy-based conditioning. Targeted conditioning using antibody-drug conjugates (ADC) holds promise for reduced toxicity in HSC therapy. Here we test ability of an conjugate targeting CD117 (CD117-ADC) to enable engraftment a non-human primate lentiviral model hemoglobinopathies. Following single-dose CD117-ADC, >99% depletion bone marrow...
Abstract Dogs ( Canis familiaris ) share many common genetic diseases with humans and development of disease models using a transgenic approach has long been awaited. However, due to the technical difficulty in obtaining fertilizable eggs unavailability embryonic stem cells, no dog generated. Canine fetal fibroblasts were stably transfected red fluorescent protein RFP gene‐expressing construct retrovirus gene delivery method. Somatic cell nuclear transfer was then employed replace nucleus an...
Critically short telomeres activate p53-mediated apoptosis, resulting in organ failure and leading to malignant transformation. Mutations genes responsible for telomere maintenance are linked a number of human diseases. We derived induced pluripotent stem cells (iPSCs) from 4 patients with aplastic anemia or hypocellular bone marrow carrying heterozygous mutations the telomerase reverse transcriptase (TERT) RNA component (TERC) genes. Both mutant control iPSCs upregulated TERT TERC...
Induced pluripotent stem cell (iPSC) therapies offer a promising path for patient-specific regenerative medicine. However, tumor formation from residual undifferentiated iPSC or transformation of their derivatives is risk. Inclusion suicide gene one approach to risk mitigation. We introduced dimerizable-"inducible caspase-9" (iCasp9) into mouse (miPSC) and rhesus (RhiPSC) via lentivirus, driving expression either cytomegalovirus (CMV), elongation factor-1 α (EF1α) pluripotency-specific...
Lentiviral vectors (LVs) are used for delivery of genes into hematopoietic stem and progenitor cells (HSPCs) in clinical trials worldwide. LVs, contrast to retroviral vectors, not associated with insertion site-associated malignant clonal expansions and, thus, considered safer. Here, however, we present a case markedly abnormal dysplastic hematopoiesis affecting the erythroid, myeloid, megakaryocytic lineages rhesus macaque transplanted HSPCs that were transduced LV containing strong murine...
Nonhuman primate (NHP) induced pluripotent stem cells (iPSCs) offer the opportunity to investigate safety, feasibility, and efficacy of proposed iPSC-derived cellular delivery in clinically relevant vivo models. However, there is need for stable, robust, safe labeling methods NHP iPSCs their differentiated lineages study survival, proliferation, tissue integration, biodistribution following transplantation. Here we utility adeno-associated virus integration site 1 (AAVS1) as a harbor...
Abstract We report the creation of a transgenic dog that conditionally expresses eGFP (enhanced green fluorescent protein) under regulation doxycycline. Briefly, fetal fibroblasts infected with Tet‐on vector were used for somatic cell nuclear transfer. Subsequently reconstructed oocytes transferred to recipients. Three clones having transgenes born and one was alive. The showed all features inducible expression upon doxycycline administration, successful breeding resulted in eGFP‐positive...
Abstract Macrophages orchestrate tissue immunity from the initiation and resolution of antimicrobial immune responses to repair damaged tissue. Murine studies demonstrate that tissue-resident macrophages are a heterogenous mixture yolk sac–derived cells populate before birth, bone marrow–derived replacements recruited in adult tissues at steady-state increased numbers response damage or infection. How this translates species constantly under immunologic challenge, such as humans, is unknown....
Summary The oocyte is known from recent studies in the mouse, cow, sheep and human to be a central regulator of follicular cell function. However, pig, little information about regulation cumulus expansion by oocyte-secreted factors quality. We investigated possible effects during vitro maturation on porcine oocytes as judged subsequent embryonic development after parthenogenetic activation. Cumulus–oocyte complexes (COC) antral follicles pig ovaries collected local abattoir were divided...
The addition of 9-cis retinoic acid to the oocyte maturation culture medium has a beneficial effect on in vitro fertilized embryos. However, mechanism this activity is not known. Therefore, study was done elucidate parthenogenetic embryo production and its signaling pathway molecular function during porcine cumulus cell-oocyte complexes (COCs). Concentrations 0, 5, 50, 500 nM were added medium, embryos assessed after activation. Cumulus cells oocytes from matured COCs separated subjected...
Abstract Nonhuman primate (NHP) models are more predictive than rodent for developing induced pluripotent stem cell (iPSC)-based therapy, but robust and reproducible NHP iPSC-cardiomyocyte differentiation protocols lacking cardiomyopathies research. We developed a method to differentiate integration-free rhesus macaque iPSCs (RhiPSCs) into cardiomyocytes with >85% purity in 10 days, using fully chemically defined conditions. To enable visualization of intracellular calcium flux beating...
The programmable nuclease technology CRISPR-Cas9 has revolutionized gene editing in the last decade. Due to risk of off-target editing, accurate and sensitive methods for characterization are crucial prior applying therapeutically. Here, we utilized a rhesus macaque model compare predictive values CIRCLE-seq, an vitro prediction method, with silico (ISP) based solely on genomic sequence comparisons. We use AmpliSeq HD error-corrected sequencing validate sites predicted by CIRCLE-seq ISP CD33...
The CRISPR-Cas9 system has emerged as a powerful and efficient tool for genome editing. An important drawback of the is constitutive endonuclease activity when Cas9 its sgRNA are co-expressed. This results in undesirable off-target effects that hinder studies using system, such probing gene functions or therapeutic use humans. Here, we describe convenient method allows temporal tight control by combining transcriptional regulation expression protein stability human stem cells. To achieve...