Concise Review: Review and Perspective of Cell Dosage and Routes of Administration From Preclinical and Clinical Studies of Stem Cell Therapy for Heart Disease

Stem Cells Transl Med. 2016 Feb;5(2):186-91. doi: 10.5966/sctm.2015-0101. Epub 2015 Dec 18.


An important stage in the development of any new therapeutic agent is establishment of the optimal dosage and route of administration. This can be particularly challenging when the treatment is a biologic agent that might exert its therapeutic effects via complex or poorly understood mechanisms. Multiple preclinical and clinical studies have shown paradoxical results, with inconsistent findings regarding the relationship between the cell dose and clinical benefit. Such phenomena can, at least in part, be attributed to variations in cell dosing or concentration and the route of administration (ROA). Although clinical trials of cell-based therapy for cardiovascular disease began more than a decade ago, specification of the optimal dosage and ROA has not been established. The present review summarizes what has been learned regarding the optimal cell dosage and ROA from preclinical and clinical studies of stem cell therapy for heart disease and offers a perspective on future directions. Significance: Preclinical and clinical studies on cell-based therapy for cardiovascular disease have shown inconsistent results, in part because of variations in study-specific dosages and/or routes of administration (ROA). Future preclinical studies and smaller clinical trials implementing cell-dose and ROA comparisons are warranted before proceeding to pivotal trials.

Keywords: Cardiovascular disease; Cell dosage; Route of administration; Stem cell.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Cardiac Catheters
  • Cell Count
  • Dogs
  • Evaluation Studies as Topic
  • Heart Diseases / pathology
  • Heart Diseases / therapy*
  • Humans
  • Injections, Intralesional
  • Injections, Intravenous
  • Stem Cell Transplantation / methods*
  • Stem Cells / cytology*
  • Stem Cells / physiology
  • Transplantation, Autologous
  • Transplantation, Homologous