A5042017623- Hematopoietic Stem Cell Transplantation
- CRISPR and Genetic Engineering
- Immune Cell Function and Interaction
- DNA Repair Mechanisms
- Mesenchymal stem cell research
- CAR-T cell therapy research
- Virus-based gene therapy research
- T-cell and B-cell Immunology
- Immunodeficiency and Autoimmune Disorders
- Pluripotent Stem Cells Research
- Prenatal Screening and Diagnostics
- Immunotherapy and Immune Responses
- Polyomavirus and related diseases
- RNA Interference and Gene Delivery
- Acute Lymphoblastic Leukemia research
- Neonatal Respiratory Health Research
- Toxin Mechanisms and Immunotoxins
- Monoclonal and Polyclonal Antibodies Research
- Biomedical Ethics and Regulation
- Acute Myeloid Leukemia Research
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- Cancer Cells and Metastasis
- Language and Culture
- Telomeres, Telomerase, and Senescence
Stanford University
2013-2025
California Institute for Regenerative Medicine
2009-2024
Lucile Packard Children's Hospital
2019-2024
Stanford Medicine
2019-2024
Harvard University
2012-2019
Harvard Stem Cell Institute
2016-2019
Boston Children's Hospital
2012-2019
Dana-Farber Cancer Institute
2016-2019
Cancer Institute (WIA)
2019
Stanford Cancer Institute
2019
Upon intravenous transplantation, hematopoietic stem cells (HSCs) can home to specialized niches, yet most HSCs fail engraft unless recipients are subjected toxic preconditioning. We provide evidence that, aside from immune barriers, donor HSC engraftment is restricted by occupancy of appropriate niches host HSCs. Administration ACK2, an antibody that blocks c-kit function, led the transient removal >98% endogenous in immunodeficient mice. Subsequent transplantation these mice with chimerism...
Despite recent advances in radiotherapy, loco-regional failures are still the leading cause of death many cancer patients. We have previously reported that bone marrow-derived CD11b + myeloid cells recruited to tumors grown irradiated tissues, thereby restoring vasculature and tumor growth. In this study, we examined whether neutralizing monoclonal antibodies could inhibit recruitment into their regrowth. observed a significant enhancement antitumor response radiation squamous cell carcinoma...
Abstract Hematopoietic stem cell transplantation (HSCT) is a curative therapy for blood and immune diseases with potential many settings beyond current standard-of-care. Broad HSCT application currently precluded largely due to morbidity mortality associated genotoxic irradiation or chemotherapy conditioning. Here we show that single dose of CD117-antibody-drug-conjugate (CD117-ADC) saporin leads > 99% depletion host HSCs, enabling rapid efficient donor hematopoietic engraftment....
The aging of tissue-specific stem and progenitor cells is believed to be central the pathophysiological conditions arising in aged individuals. While mechanisms driving cell are poorly understood, mounting evidence points age-dependent DNA damage accrual as an important contributing factor. it has been postulated that may deplete numbers with age, recent studies indicate murine hematopoietic (HSC) reserves fact maintained despite genomic age. Evidence suggests this a result quiescent (G0)...
Significance Hematopoietic stem cells (HSCs) are the key therapeutic component of bone marrow transplantation, first and most prevalent clinical cell therapy. HSCs sustain daily life-long blood immune production through a complex stepwise lineage commitment process. In this work, we analyzed HSC at clonal level identified regulatory mechanisms that undetectable by conventional population-level studies. We uncovered distinct pathways lead to differential imbalances. Furthermore, showed...
Hematopoietic stem cell transplantation (HSCT) is the only definitive cure for pediatric acute myeloid leukemia (AML). Despite adjustments in HSCT protocols and improvements supportive care, 30% of high-risk patients who receive as part their therapy still experience disease relapse with high transplant-related mortality. Relapsed AML has a dismal prognosis, novel therapies are needed. To improve upon status quo, would more effectively eliminate relapse-initiating leukemic cells be delivered...
Hematopoietic stem cells (HSCs) are thought to reside in discrete niches through stable adhesion, yet previous studies have suggested that host HSCs can be replaced by transplanted donor HSCs, even the absence of cytoreductive conditioning. To explain this apparent paradox, we calculated, cell surface phenotyping and transplantation unfractionated blood, ∼1–5% total pool enters into circulation each day. Bromodeoxyuridine (BrdU) feeding experiments demonstrated peripheral blood incorporate...
Hematopoietic stem cells (HSCs) are a rare type of hematopoietic cell that can entirely reconstitute the blood and immune system after transplantation. Allogeneic HSC transplantation (HSCT) is used clinically as curative therapy for range hematolymphoid diseases; however, it remains high-risk because its potential side effects, including poor graft function graft-versus-host disease (GVHD). Ex vivo expansion has been suggested an approach to improve reconstitution in low-cell dose grafts....
Key Points Hematopoietic cell–targeted antibody-drug conjugate preconditioning is highly effective for platelet gene therapy in hemophilia A mice. Platelet-specific FVIII can effectively prevent a needle-induced knee joint injury
Abstract Hematopoietic chimerism after allogeneic bone marrow transplantation may establish a state of donor antigen-specific tolerance. However, current allotransplantation protocols involve genotoxic conditioning which has harmful side-effects and predisposes to infection cancer. Here we describe non-genotoxic protocol for fully MHC-mismatched in mice involving transient immunosuppression selective depletion recipient hematopoietic stem cells with CD117-antibody-drug-conjugate (ADC). This...
Gastrointestinal stromal tumor (GIST) is the most common sarcoma of gastrointestinal tract and arises from interstitial cells Cajal. It characterized by expression receptor tyrosine kinase CD117 (KIT). In 70–80% GIST cases, oncogenic mutations in KIT are present, leading to constitutive activation receptor, which drives proliferation these tumors. Treatment with imatinib, a small-molecule inhibitor, inhibits KIT-mediated signaling initially results disease control 70–85% patients...
In vivo gene therapy targeting hematopoietic stem cells (HSCs) holds significant therapeutic potential for treating hematological diseases. This study uses adeno-associated virus serotype 6 (AAV6) vectors and Cre recombination to systematically optimize the parameters effective in HSC transduction. We evaluated various genetic architectures delivery methods of AAV6, establishing an optimized protocol that achieved functional more than two-thirds immunophenotypic HSCs. Our findings highlight...