Browsing by Author "Court, Angela C."
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Item Court, Angela C.Court, Angela C.Item Court, Angela C.Court, Angela C.Item Mitochondrial transfer balances cell redox, energy and metabolic homeostasis in the osteoarthritic chondrocyte preserving cartilage integrityCourt, Angela C.; Vega-Letter, Ana María; Parra-Crisóstomo, Eliseo; Velarde, Francesca; García, Cynthia; Ortloff, Alexander; Vernal, Rolando; Pradenas, Carolina; Luz-Crawford, Patricia; Khoury, Maroun; Figueroa, Fernando E.Item Mitochondrial transfer balances cell redox, energy and metabolic homeostasis in the osteoarthritic chondrocyte preserving cartilage integrityCourt, Angela C.; Vega-Letter, Ana María; Parra-Crisóstomo, Eliseo; Velarde, Francesca; García, Cynthia; Ortloff, Alexander; Vernal, Rolando; Pradenas, Carolina; Luz-Crawford, Patricia; Khoury, Maroun; Figueroa, Fernando E.Item Mitochondrial transfer balances cell redox, energy and metabolic homeostasis in the osteoarthritic chondrocyte preserving cartilage integrityCourt, Angela C.; Vega-Letter, Ana María; Parra-Crisóstomo, Eliseo; Velarde, Francesca; García, Cynthia; Ortloff, Alexander; Vernal, Rolando; Pradenas, Carolina; Luz-Crawford, Patricia; Khoury, Maroun; Figueroa, Fernando E.Item Mitochondrial transfer from MSCs to T cells induces Treg differentiation and restricts inflammatory responseCourt, Angela C.; Le-Gatt, Alice; Luz-Crawford, Patricia; Parra, Eliseo; Aliaga-Tobar, Victor; Bátiz, Luis Federico; Contreras, Rafael A.; Ortúzar, María Ignacia; Kurte, Mónica; Elizondo-Vega, Roberto; Maracaja-Coutinho, Vinicius; Pino-Lagos, Karina; Figueroa, Fernando E.; Khoury, MarounItem Mitochondrial transfer from MSCs to T cells induces Treg differentiation and restricts inflammatory responseCourt, Angela C.; Le-Gatt, Alice; Luz-Crawford, Patricia; Parra, Eliseo; Aliaga-Tobar, Victor; Bátiz, Luis Federico; Contreras, Rafael A.; Ortúzar, María Ignacia; Kurte, Mónica; Elizondo-Vega, Roberto; Maracaja-Coutinho, Vinicius; Pino-Lagos, Karina; Figueroa, Fernando E.; Khoury, MarounItem Mitochondrial transfer from MSCs to T cells induces Treg differentiation and restricts inflammatory responseCourt, Angela C.; Le-Gatt, Alice; Luz-Crawford, Patricia; Parra, Eliseo; Aliaga-Tobar, Victor; Bátiz, Luis Federico; Contreras, Rafael A.; Ortúzar, María Ignacia; Kurte, Mónica; Elizondo-Vega, Roberto; Maracaja-Coutinho, Vinicius; Pino-Lagos, Karina; Figueroa, Fernando E.; Khoury, MarounItem Survival advantage of native and engineered T cells is acquired by mitochondrial transfer from mesenchymal stem cells(Journal of Translational Medicine, 2024-12) Court, Angela C.; Parra Crisóstomo, Eliseo; Castro Córdova, Pablo; Lorca, Rocío; Figueroa, Fernando E.; Khoury, MarounBackground: Apoptosis, a form of programmed cell death, is critical for the development and homeostasis of the immune system. Chimeric antigen receptor T (CAR-T) cell therapy, approved for hematologic cancers, retains several limitations and challenges associated with ex vivo manipulation, including CAR T-cell susceptibility to apoptosis. Therefore, strategies to improve T-cell survival and persistence are required. Mesenchymal stem/stromal cells (MSCs) exhibit immunoregulatory and tissue-restoring potential. We have previously shown that the transfer of umbilical cord MSC (UC-MSC)-derived mitochondrial (MitoT) prompts the genetic reprogramming of CD3+ T cells towards a Treg cell lineage. The potency of T cells plays an important role in effective immunotherapy, underscoring the need for improving their metabolic fitness. In the present work, we evaluate the effect of MitoT on apoptotis of native T lymphocytes and engineered CAR-T cells. Methods: We used a cell-free approach using artificial MitoT (Mitoception) of UC-MSC derived MT to peripheral blood mononuclear cells (PBMCs) followed by RNA-seq analysis of CD3+ MitoTpos and MitoTneg sorted cells. Target cell apoptosis was induced with Staurosporine (STS), and cell viability was evaluated with Annexin V/7AAD and TUNEL assays. Changes in apoptotic regulators were assessed by flow cytometry, western blot, and qRT-PCR. The effect of MitoT on 19BBz CAR T-cell apoptosis in response to electroporation with a non-viral transposon-based vector was assessed with Annexin V/7AAD. Results: Gene expression related to apoptosis, cell death and/or responses to different stimuli was modified in CD3+ T cells after Mitoception. CD3+MitoTpos cells were resistant to STS-induced apoptosis compared to MitoTneg cells, showing a decreased percentage in apoptotic T cells as well as in TUNEL+ cells. Additionally, MitoT prevented the STS-induced collapse of the mitochondrial membrane potential (MMP) levels, decreased caspase-3 cleavage, increased BCL2 transcript levels and BCL-2-related BARD1 expression in FACS-sorted CD3+ T cells. Furthermore, UC-MSC-derived MitoT reduced both early and late apoptosis in CAR-T cells following electroporation, and exhibited an increasing trend in cytotoxic activity levels. Conclusions: Artificial MitoT prevents STS-induced apoptosis of human CD3+ T cells by interfering with the caspase pathway. Furthermore, we observed that MitoT confers protection to apoptosis induced by electroporation in MitoTpos CAR T-engineered cells, potentially improving their metabolic fitness and resistance to environmental stress. These results widen the physiological perspective of organelle-based therapies in immune conditions while offering potential avenues to enhance CAR-T treatment outcomes where their viability is compromised.Item Survival advantage of native and engineered T cells is acquired by mitochondrial transfer from mesenchymal stem cellsCourt, Angela C.; Parra-Crisóstomo, Eliseo; Castro-Córdova, Pablo; Abdo, Luiza; Aragão, Emmanuel Arthur Albuquerque; Lorca, Rocío; Figueroa, Fernando E.; Bonamino, Martín Hernán; Khoury, MarounItem Survival advantage of native and engineered T cells is acquired by mitochondrial transfer from mesenchymal stem cellsCourt, Angela C.; Parra-Crisóstomo, Eliseo; Castro-Córdova, Pablo; Abdo, Luiza; Aragão, Emmanuel Arthur Albuquerque; Lorca, Rocío; Figueroa, Fernando E.; Bonamino, Martín Hernán; Khoury, MarounItem Survival advantage of native and engineered T cells is acquired by mitochondrial transfer from mesenchymal stem cellsCourt, Angela C.; Parra-Crisóstomo, Eliseo; Castro-Córdova, Pablo; Abdo, Luiza; Aragão, Emmanuel Arthur Albuquerque; Lorca, Rocío; Figueroa, Fernando E.; Bonamino, Martín Hernán; Khoury, Maroun