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Mechanisms of Cell Therapy for Clinical Investigations  27.01.2016 09:13

An Urgent Need for Large-Animal Models

  1. Jianyi Jay Zhang, MD, PhD

+Author Affiliations

  1. From the Cardiovascular Division, Department of Medicine, University of Minnesota Medical School, Minneapolis.
  1. Correspondence to Jianyi Jay Zhang, MD, PhD, MMC 508, Division of Cardiology, Department of Medicine, University of Minnesota Medical School, Minneapolis, MN 55455. E-mail zhang047@umn.edu
Key Words:

Introduction

Evidence from experiments performed in animal models and from early-stage clinical trials demonstrates that the contractile performance of hearts with severe ischemic injury can be improved by transplanting a variety of cell types into the injured heart1–5 As a result of these investigations, progenitor cells have emerged as a promising therapeutic agent not only for limiting postinfarction left ventricular (LV) remodeling, but also for improving cardiac performance in hearts with severe LV dysfunction secondary to other diseases such as dilated cardiomyopathy and concentric LV hypertrophy.6,7 Some of the most encouraging clinical results were obtained in the Cardiac Stem Cells in Patients With Ischaemic Cardiomyopathy (SCIPIO) trial,4 which investigated the use of autologous cardiac progenitor cells (CPCs) in patients with severe LV dysfunction undergoing coronary artery bypass graft surgery. Although the small patient population and open-label design preclude definitive mechanistic conclusions, CPC infusion was associated with significant improvements in LV ejection fraction from before treatment to 4 months afterward, and even greater improvement was observed at 12 months. These and other promising results could soon lead to the initiation of more definitive, large-scale, phase 2 clinical trials.

Article see p 122

Novel therapies have often been adopted into clinical practice before their mechanisms of action have been completely deciphered, provided that their safety and beneficial effects are reproducible. For the emerging cellular therapy, however, the optimal cell type, dose, timing, and route of administration need to be identified to ensure that cell therapies produce …

Полный текст статьи      http://circ.ahajournals.org/content/128/2/92.full



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