Celularity Tissue Factor Gene Knockout Of Allogeneic Stromal Cells Significantly Lowers Thrombotic Effects; Study Highlights Critical Importance Of Gene Editing Capability
Data published online in the journal Cytotherapy demonstrate that CRISPR-mediated tissue factor gene knockout (TFKO) in allogeneic stromal cells (ASCs) leads to significantly lower tissue factor (TF) expression, activity, and thrombotic effects, providing a feasible strategy potentially to improve the safety of ASC-based cell therapy
FLORHAM PARK, N.J., June 1, 2023 – Celularity Inc. (Nasdaq: CELU) (“Celularity”), a biotechnology company developing placental-derived allogeneic cell therapies and biomaterial products, announced today the online publication of preclinical data in Cytotherapy, the official journal of the International Society of Cell and Gene Therapy (ISCT).
The paper, “Characterization of CRISPR/Cas9-edited human placental allogenic stromal cells with low tissue factor expression and reduced thrombotic effects,” (Huang, et al.) examined methods to reduce the tissue factor expressed by allogeneic stromal cells (ASCs), which has been regarded as a safety concern in clinical applications as it may trigger thrombosis when ASCs are administered intravenously.
Thrombogenic risk has been identified in association with intravenous administration of mesenchymal stem cells (MSCs), both allogeneic and autologous. These cells express procoagulant activity linked to the expression of tissue factor that, when in contact with blood, initiates coagulation. Mitigating thrombotic risk is of significant clinical importance.
Placenta ASCs are MSC-like cells, cultured and expanded from full-term human placenta with a defined phenotype, demonstrate immunomodulation and pro-regenerative activities and have been investigated in clinical trials of Crohn’s disease, diabetic foot ulcer, and multiple sclerosis. The authors characterized and compared in vitro and in vivo activities of ASCs with CRISPR/Cas9-mediated TF gene knockout to non-edited ASCs with the goal of improving ASC clinical safety.
Using CRISPR gene editing of ASCs, the study demonstrated that efficient TFKO can be achieved, generating ASCs with significantly reduced TF activity without affecting the critical features and functions of the cells. The authors concluded that the TF gene knockout provides a feasible strategy which may improve the clinical safety features of ASC-based cell therapies.
“We are very encouraged by these results with an edited version of one of our cell therapy candidates,” said Robert J. Hariri, M.D., Ph.D., Celularity’s CEO, Chairman and Founder. “These data advance our understanding of the potential for ASCs to safely address human diseases. These data also are guiding our investment decision to progress our novel genetically modified allogeneic placental-derived mesenchymal-like adherent stromal cells (MLASCs), APPL-001, in diseases like Crohn’s disease, facioscapulohumeral muscular dystrophy (FSHD), and to explore a range of other clinical indications.”
Celularity Inc. (Nasdaq: CELU) headquartered in Florham Park, N.J., is a biotechnology company leading the next evolution in cellular and regenerative medicine by developing allogeneic cryopreserved off-the-shelf placental-derived cell therapies, including therapeutic programs using mesenchymal-like adherent stromal cells (MLASCs), T-cells engineered with CAR (CAR T-cells), and genetically modified and unmodified natural killer (NK) cells. These therapeutic programs target indications in autoimmune, infectious and degenerative diseases, and cancer. In addition, Celularity develops, manufactures, and commercializes innovative biomaterial products also derived from the postpartum placenta. Celularity believes that by harnessing the placenta’s unique biology and ready availability, it can develop therapeutic solutions that address significant unmet global needs for effective, accessible, and affordable therapies.
To learn more, visit celularity.com
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