Article

CT for Evaluation of Myocardial Cell Therapy in Heart Failure A Comparison With CMR Imaging

Department of Medicine, Division of Cardiology, Johns Hopkins University, Baltimore, MD 21205, USA.
JACC. Cardiovascular imaging (Impact Factor: 6.99). 12/2011; 4(12):1284-93. DOI: 10.1016/j.jcmg.2011.09.013
Source: PubMed

ABSTRACT The aim of this study was to use multidetector computed tomography (MDCT) to assess therapeutic effects of myocardial regenerative cell therapies.
Cell transplantation is being widely investigated as a potential therapy in heart failure. Noninvasive imaging techniques are frequently used to investigate therapeutic effects of cell therapies in the preclinical and clinical settings. Previous studies have shown that cardiac MDCT can accurately quantify myocardial scar tissue and determine left ventricular (LV) volumes and ejection fraction (LVEF).
Twenty-two minipigs were randomized to intramyocardial injection of phosphate-buffered saline (placebo, n = 9) or 200 million mesenchymal stem cells (MSC, n = 13) 12 weeks after myocardial infarction (MI). Cardiac magnetic resonance and MDCT acquisitions were performed before randomization (12 weeks after MI induction) and at the study endpoint 24 weeks after MI induction. None of the animals received medication to control the intrinsic heart rate during first-pass acquisitions for assessment of LV volumes and LVEF. Delayed-enhancement MDCT imaging was performed 10 min after contrast delivery. Two blinded observers analyzed MDCT acquisitions.
MDCT demonstrated that MSC therapy resulted in a reduction of infarct size from 14.3 ± 1.2% to 10.3 ± 1.5% of LV mass (p = 0.005), whereas infarct size increased in nontreated animals (from 13.8 ± 1.3% to 16.5 ± 1.5%; p = 0.02) (placebo vs. MSC; p = 0.003). Both observers had excellent agreement for infarct size (r = 0.96; p < 0.001). LVEF increased from 32.6 ± 2.2% to 36.9 ± 2.7% in MSC-treated animals (p = 0.03) and decreased in placebo animals (from 33.3 ± 1.4% to 29.1 ± 1.5%; p = 0.01; at week 24: placebo vs. MSC; p = 0.02). Infarct size, end-diastolic LV volume, and LVEF assessed by MDCT compared favorably with those assessed by cardiac magnetic resonance acquisitions (r = 0.70, r = 0.82, and r = 0.902, respectively; p < 0.001).
This study demonstrated that cardiac MDCT can be used to evaluate infarct size, LV volumes, and LVEF after intramyocardial-delivered MSC therapy. These findings support the use of cardiac MDCT in preclinical and clinical studies for novel myocardial therapies.

0 Followers
 · 
105 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Rationale: In regenerative therapy for ischemic heart disease, use of both autologous and allogeneic stem cells have been investigated. Autologous cell can be applied without immunosuppression but availability is restricted and cells have been exposed to risk factors and aging. Allogeneic cell therapy enables pre-operative production of potent cell lines and immediate availability of cell products, allowing 'off the shelf' therapy. It is unknown which cell source is preferred with regard to improving cardiac function. Objective: We performed a meta-analysis of pre-clinical data of cell therapy for ischemic heart disease. Methods and Results: We conducted a systematic literature search to identify publications describing controlled pre-clinical trials of unmodified stem cell therapy in large animal models of myocardial ischemia. Data from 82 studies involving 1415 animals showed a significant improvement in mean left ventricular ejection fraction (LVEF) in treated compared to control animals (8.3%, 95% CI 7.1 - 9.5, p <0.001). Meta-regression revealed a similar difference in LVEF in autologous (8.8% 95% CI 7.3 - 10.3 n= 981) and allogeneic (7.3% 95% CI 4.4 - 10.2 n= 331) (p= 0.3) cell therapies. Conclusions: Autologous and allogeneic cell therapy for ischemic heart disease show a similar improvement in LVEF in large animal models of myocardial ischemia, compared to placebo. These results are important for the design of future clinical trials.
    Circulation Research 08/2014; DOI:10.1161/CIRCRESAHA.116.304872 · 11.09 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Heart failure remains a major cause of death and disability, requiring rapid development of new therapies. Bone marrow-derived mesenchymal stem cell (MSC)-based therapy is an emerging approach for the treatment of both acute and chronic heart failure. Following successful experimental studies in a range of models, more than 40 clinical trials of MSC-based therapy for heart failure have now been registered, and the results of completed clinical trials so far have shown feasibility and safety of this approach with therapeutic potential suggested (though preliminarily). However, there appear to be several critical issues to be solved before this treatment could become a widespread standard therapy for heart failure. In this review, we comprehensively and systemically summarize a total of 73 preclinical studies and 11 clinical trial reports published to date. By analyzing the data in these reports, (1) improvement in the cell delivery method to the heart in order to enhance donor cell engraftment, (2) elucidation of mechanisms underpinning the therapeutic effects of the treatment differentiation and/or treatment secretion, and (3) validation of the utility of allogeneic MSCs which could enhance the efficacy and expand the application/indication of this therapeutic approach are highlighted as future perspectives. These important respects are further discussed in this review article with referencing latest scientific and clinical information.
    Heart Failure Reviews 05/2014; DOI:10.1007/s10741-014-9435-x · 3.99 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The treatment of Interstinal Cystitisis (IC) is still challenge for urologist. Available therapies do not result in long-term control of symptoms and do not provide pain relive to patients. Unique abilities of mesenchymal stem cells (MSC) could be used to develop new treatment approaches for Interstitial Cystitis. Conditioned Medium (CM) derived from MSC culture is rich in plenty of growth factors, cytokines and trophic agents which were widely reported to enhance regeneration of urinary bladder in different conditions. This ready mixture of growth factors could be used to develop intravesical therapy for patients with IC. MSC-CM has anti-apoptotic, anti-inflammatory, supportive, angiogenic, immunosuppressive and immunomodulative properties and seems to be ideal substance to prevent IC recurrence and to create favorable environment for regeneration of damaged bladder wall.
    Medical Hypotheses 03/2014; 82(6). DOI:10.1016/j.mehy.2014.02.027 · 1.15 Impact Factor

Full-text (2 Sources)

Download
43 Downloads
Available from
Jun 5, 2014