Browsing by Subject "Cell-based therapy"

Now showing 1 - 3 of 3
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    Evaluating Thera-101 as a Low-Volume Resuscitation Fluid in a Model of Polytrauma
    (MDPI, 2022-10-21) Shah, Jessica Stukel; Macaitis, Joseph; Lundquist, Bridney; Johnstone, Brian; Coleman, Michael; Jefferson, Michelle A.; Glaser, Jacob; Rodriguez, Annette R.; Cardin, Sylvain; Wang, Heuy-Ching; Burdette, Alexander; Emergency Medicine, School of Medicine
    Traumatic brain injury (TBI) and hemorrhage remain challenging to treat in austere conditions. Developing a therapeutic to mitigate the associated pathophysiology is critical to meet this treatment gap, especially as these injuries and associated high mortality are possibly preventable. Here, Thera-101 (T-101) was evaluated as low-volume resuscitative fluid in a rat model of TBI and hemorrhage. The therapeutic, T-101, is uniquely situated as a TBI and hemorrhage intervention. It contains a cocktail of proteins and microvesicles from the secretome of adipose-derived mesenchymal stromal cells that can act on repair and regenerative mechanisms associated with poly-trauma. T-101 efficacy was determined at 4, 24, 48, and 72 h post-injury by evaluating blood chemistry, inflammatory chemo/cytokines, histology, and diffusion tensor imaging. Blood chemistry indicated that T-101 reduced the markers of liver damage to Sham levels while the levels remained elevated with the control (saline) resuscitative fluid. Histology supports the potential protective effects of T-101 on the kidneys. Diffusion tensor imaging showed that the injury caused the most damage to the corpus callosum and the fimbria. Immunohistochemistry suggests that T-101 may mitigate astrocyte activation at 72 h. Together, these data suggest that T-101 may serve as a potential field deployable low-volume resuscitation therapeutic.
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    Getting A Leg Up on Cell Therapy for Critical Limb Ischemia
    (American Heart Association, 2017-04-14) Wang, S. Keisin; Murphy, Michael P.; Surgery, School of Medicine
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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.