Cardiac cell-repair therapy: clinical issues.
The possibility that cardiac cell-repair therapy might become a clinical reality is a challenge worthy of the current state of technological and scientific expertise at the start of the 21(st) century. The success of preclinical and early clinical studies is a strong inducement to move ahead with larger clinical trials, but caution is warranted given our lack of understanding of the potential mechanisms by which cell-repair therapy exerts a benefit on ventricular function, perfusion, and infarct size, irrespective of the type of cell, method, site, and disease entity. There are multiple clinical, mechanistic, and safety questions requiring answers, and these will be forthcoming only if the design of clinical trials is carefully tailored to answer specific questions. These questions, in turn, will require the use of different and multiple end points, depending on the specific issue and study. Accordingly, this review addresses the limitations of current clinical studies, the design of future trials, and the concept of a hierarchical series of end points that might provide answers to a host of different questions. Clinical and basic scientists need to approach the next generation of trials in partnership.
Gersh
Bernard J
BJ
Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic College of Medicine, Mayo Clinic and Mayo Foundation, Rochester, MN 55905, USA. gersh.bernard@mayo.edu
Simari
Robert D
RD
D000818:Animals; D002986:Clinical Trials as Topic; D023381:Endpoint Determination; D006331:Heart Diseases / Q000628:therapy*; D006801:Humans; D044968:Regenerative Medicine / Q000639:trends; D012107:Research Design; D033581:Stem Cell Transplantation / Q000009:adverse effects*