Therapeutic time window and dose response of autologous bone marrow mononuclear cells for ischemic stroke

J Neurosci Res. 2011 Jun;89(6):833-9. doi: 10.1002/jnr.22614. Epub 2011 Mar 15.

Abstract

Although mononuclear cells (MNCs) from bone marrow are being investigated in phase I clinical trials in stroke patients, dose response, therapeutic time window, and biodistribiton have not been well-characterized in animal stroke models. Long Evans rats underwent common carotid artery/middle cerebral artery occlusion (CCA/MCAo) and 24 hr later were randomized to receive saline IV or a bone marrow aspiration followed by an IV infusion of autologous separated MNCs (1 million, 10 million, or 30 million cells/kg). In another experiment, rats underwent CCAo/MCAo and were randomized at 24 hr, 72 hr, or 7 days after stroke to receive a saline injection or 10 million/kg MNCs. All animals were evaluated on the cylinder and corner tests up to 28 days. MNCs were tracked using Q-dot nanocrystals to monitor biodistribution. Animals treated with MNCs at 10 million and 30 million cells/kg at 24 hr after stroke had significant reductions in neurological deficits and lesion size compared with saline controls or animals treated with 1 million cells/kg. There was no difference in neurological deficits in the 10 and 30 million cell/kg groups at 28 days. Animals treated with MNCs at 72 hr but not at 7 days showed a significant reduction in neurological deficits by 28 days. Labeled MNCs were found in the brain, spleen, lung, liver, and kidney at 1 hr and exponentially decreased over the ensuing week. In conclusion, we found a maximum reduction in neurological deficits at 10 and 30 million cells/kg and a therapeutic time window up to 72 hr after stroke. © 2011 Wiley-Liss, Inc.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Bone Marrow Cells / physiology*
  • Bone Marrow Transplantation / methods*
  • Brain Infarction / etiology
  • Brain Infarction / pathology
  • Disease Models, Animal
  • Infarction, Middle Cerebral Artery / complications
  • Infarction, Middle Cerebral Artery / surgery*
  • Injections, Intravenous / methods
  • Male
  • Movement Disorders / etiology
  • Rats
  • Rats, Long-Evans
  • Time Factors
  • Transplantation, Autologous