Browsing by Author "Khan, Aisha"

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    Magnetic separation of peripheral nerve-resident cells underscores key molecular features of human Schwann cells and fibroblasts: an immunochemical and transcriptomics approach
    (Nature Publishing Group, 2020-10-28) Peng, Kaiwen; Sant, David; Andersen, Natalia; Silvera, Risset; Camarena, Vladimir; Piñero, Gonzalo; Graham, Regina; Khan, Aisha; Xu, Xiao-Ming; Wang, Gaofeng; Monje, Paula V.; Neurological Surgery, School of Medicine
    Nerve-derived human Schwann cell (SC) cultures are irreplaceable models for basic and translational research but their use can be limited due to the risk of fibroblast overgrowth. Fibroblasts are an ill-defined population consisting of highly proliferative cells that, contrary to human SCs, do not undergo senescence in culture. We initiated this study by performing an exhaustive immunological and functional characterization of adult nerve-derived human SCs and fibroblasts to reveal their properties and optimize a protocol of magnetic-activated cell sorting (MACS) to separate them effectively both as viable and biologically competent cells. We next used immunofluorescence microscopy imaging, flow cytometry analysis and next generation RNA sequencing (RNA-seq) to unambiguously characterize the post-MACS cell products. High resolution transcriptome profiling revealed the identity of key lineage-specific transcripts and the clearly distinct neural crest and mesenchymal origin of human SCs and fibroblasts, respectively. Our analysis underscored a progenitor- or stem cell-like molecular phenotype in SCs and fibroblasts and the heterogeneity of the fibroblast populations. In addition, pathway analysis of RNA-seq data highlighted putative bidirectional networks of fibroblast-to-SC signaling that predict a complementary, yet seemingly independent contribution of SCs and fibroblasts to nerve regeneration. In sum, combining MACS with immunochemical and transcriptomics approaches provides an ideal workflow to exhaustively assess the identity, the stage of differentiation and functional features of highly purified cells from human peripheral nerve tissues.
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    A Phase II study of autologous mesenchymal stromal cells and c-kit positive cardiac cells, alone or in combination, in patients with ischaemic heart failure: the CCTRN CONCERT-HF trial
    (Wiley, 2021-04) Bolli, Roberto; Mitrani, Raul D.; Hare, Joshua M.; Pepine, Carl J.; Perin, Emerson C.; Willerson, James T.; Traverse, Jay H.; Henry, Timothy D.; Yang, Phillip C.; Murphy, Michael P.; March, Keith L.; Schulman, Ivonne H.; Ikram, Sohail; Lee, David P.; O’Brien, Connor; Lima, Joao A.; Ostovaneh, Mohammad R.; Ambale-Venkatesh, Bharath; Lewis, Gregory; Khan, Aisha; Bacallao, Ketty; Valasaki, Krystalenia; Longsomboon, Bangon; Gee, Adrian P.; Richman, Sara; Taylor, Doris A.; Lai, Dejian; Sayre, Shelly L.; Bettencourt, Judy; Vojvodic, Rachel W.; Cohen, Michelle L.; Simpson, Lara; Aguilar, David; Loghin, Catalin; Moyé, Lem; Ebert, Ray F.; Davis, Barry R.; Simari, Robert D.; Surgery, School of Medicine
    Aims: CONCERT-HF is an NHLBI-sponsored, double-blind, placebo-controlled, Phase II trial designed to determine whether treatment with autologous bone marrow-derived mesenchymal stromal cells (MSCs) and c-kit positive cardiac cells (CPCs), given alone or in combination, is feasible, safe, and beneficial in patients with heart failure (HF) caused by ischaemic cardiomyopathy. Methods and results: Patients were randomized (1:1:1:1) to transendocardial injection of MSCs combined with CPCs, MSCs alone, CPCs alone, or placebo, and followed for 12 months. Seven centres enrolled 125 participants with left ventricular ejection fraction of 28.6 ± 6.1% and scar size 19.4 ± 5.8%, in New York Heart Association class II or III. The proportion of major adverse cardiac events (MACE) was significantly decreased by CPCs alone (-22% vs. placebo, P = 0.043). Quality of life (Minnesota Living with Heart Failure Questionnaire score) was significantly improved by MSCs alone (P = 0.050) and MSCs + CPCs (P = 0.023) vs. placebo. Left ventricular ejection fraction, left ventricular volumes, scar size, 6-min walking distance, and peak oxygen consumption did not differ significantly among groups. Conclusions: This is the first multicentre trial assessing CPCs and a combination of two cell types from different tissues in HF patients. The results show that treatment is safe and feasible. Even with maximal guideline-directed therapy, both CPCs and MSCs were associated with improved clinical outcomes (MACE and quality of life, respectively) in ischaemic HF without affecting left ventricular function or structure, suggesting possible systemic or paracrine cellular mechanisms. Combining MSCs with CPCs was associated with improvement in both these outcomes. These results suggest potential important beneficial effects of CPCs and MSCs and support further investigation in HF patients.