Intra-arterial bone marrow mononuclear cells in ischemic stroke: a pilot clinical trial

Stroke. 2012 Aug;43(8):2242-4. doi: 10.1161/STROKEAHA.112.659409. Epub 2012 Jul 3.

Abstract

Background and purpose: Bone marrow mononuclear cell (BM-MNC) intra-arterial transplantation improves recovery in experimental models of ischemic stroke. We aimed to assess the safety, feasibility, and biological effects of autologous BM-MNC transplantation in patients with stroke.

Methods: A single-blind (outcomes assessor) controlled Phase I/II trial was conducted in patients with middle cerebral artery stroke. Autologous BM-MNCs were injected intra-arterially between 5 and 9 days after stroke. Follow-up was done for up to 6 months and blood samples were collected for biological markers. The primary outcome was safety and feasibility of the procedure. The secondary outcome was improvement in neurological function.

Results: Ten cases (BM-MNC-treated) and 10 control subjects (BM-MNC-nontreated) were consecutively included. Mean National Institutes of Health Stroke Scale before the procedure was 15.6. Mean BM-MNCs injected were 1.59×10(8). There was no death, stroke recurrence, or tumor formation during follow-up, although 2 cases had an isolate partial seizure at 3 months. After transplantation, higher plasma levels of beta nerve growth factor (β-nerve growth factor) were found compared with control subjects (P=0.02). There were no significant differences in neurological function at 180 days. A trend to positive correlation between number of CD34+ cells injected and Barthel Index was found (r=0.56, P=0.09).

Conclusions: Intra-arterial BM-MNC transplantation in subacute ischemic stroke is feasible and seems to be safe. Larger randomized trials are needed to confirm the safety and elucidate the efficacy of BM-MNC transplantation.

Clinical trial registration url: www.clinicaltrials.gov. Unique identifier: NCT00761982.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, CD34
  • Bone Marrow Transplantation / adverse effects
  • Bone Marrow Transplantation / methods*
  • Brain Ischemia / therapy*
  • Female
  • Granulocyte Colony-Stimulating Factor / blood
  • Hemodynamics / physiology
  • Humans
  • Infarction, Middle Cerebral Artery / complications
  • Infarction, Middle Cerebral Artery / therapy
  • Male
  • Middle Aged
  • Nerve Growth Factor / blood
  • Neurologic Examination
  • Pilot Projects
  • Safety
  • Stroke / therapy*
  • Treatment Outcome
  • Young Adult

Substances

  • Antigens, CD34
  • Granulocyte Colony-Stimulating Factor
  • Nerve Growth Factor

Associated data

  • ClinicalTrials.gov/NCT00761982