Stem cell transplantation for ischemic stroke.
BACKGROUND
Studies in animal models of ischemic stroke have shown that stem cells transplanted into the brain can lead to functional improvement. However, to date, evidence for the benefits of stem cell transplantation in ischemic stroke patients is lacking.


OBJECTIVE
To assess the efficacy and safety of stem cell transplantation compared with conventional treatments in patients with ischemic stroke.


METHODS
We searched the Cochrane Stroke Group Trials Register (last searched February 2010), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, Issue 3), MEDLINE (1966 to August 2008), EMBASE (1980 to August 2008), Science Citation Index (1900 to August 2008), and BIOSIS (1926 to August 2008). We handsearched potentially relevant conference proceedings, screened reference lists, and searched ongoing trials and research registers (last searched November 2008). We also contacted individuals active in the field and stem cell manufacturers (last contacted December 2008).


METHODS
We included randomized controlled trials (RCTs) recruiting patients with ischemic stroke, in any phase of the disease, and an ischemic lesion confirmed by computerized tomography or magnetic resonance imaging scan. We included all types of stem cell transplantation regardless of cell source (autograft, allograft, or xenograft; embryonic, fetal, or adult; from brain or other tissues), route of cell administration (systemic or local), and dosage. The primary outcome was efficacy (assessed as combined functional outcome or disability and dependency) at longer follow-up (minimum six months). Secondary outcomes included post-procedure safety outcomes (death, worsening of neurological deficit, infections and neoplastic transformation).


METHODS
Two review authors independently extracted data and assessed trial quality. We contacted study authors for additional information.


RESULTS
We identified three very small RCTs. Two are still awaiting classification because only subgroups of patients could be included in this meta-analysis and additional unpublished data are needed. The third trial randomized 30 patients to intravenous transplantation of autologous mesenchymal stem cell (10 participants) or reference group (20 participants) (five participants, initially randomized to the intervention group, refused the treatment and were allocated to the reference group) and found a statistically non-significant functional improvement in treated patients at longer follow-up. No adverse cell-related events were reported.


CONCLUSIONS
No large trials of stem cell transplantation have been performed in ischemic stroke patients and it is too early to know whether this intervention can improve functional outcome. Large, well-designed trials are needed.
Boncoraglio
Giorgio Battista
GB
Department of Neurology, Fondazione IRCCS Istituto Neurologico "Carlo Besta", Via Celoria 11, Milano, Italy, 20133.
Bersano
Anna
A
Candelise
Livia
L
Reynolds
Brent A
BA
Parati
Eugenio A
EA
D000208:Acute Disease; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000534:rehabilitation / Q000601:surgery*; D045164:Mesenchymal Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods; D016032:Randomized Controlled Trials as Topic; D033581:Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D020521:Stroke / Q000601:surgery*