Table 1.
Trials with Published Clinical Results
Study reference/Country | Study design | Route | Cell type | Type of stroke | Age range (mean) | Time range from stroke onset to transplantation | No. of treated patients (No. of controls) | No. of cells injected | Infusion volume, rate and duration | Follow-up |
---|---|---|---|---|---|---|---|---|---|---|
Kondziolka et al., 2000/United States | Phase I, nonrandomized, single-blind | IC | NT2N cells | Ischemic stroke in basal ganglia (8 cases) or cortex and basal ganglia (4 cases) | 44–75 | 7 to 55 months (mean 27 months) | 12 (no controls) | 2×106 (8 patients); 6×106 (4 patients) | Not specified | 52–60 months |
Rabinovich et al., 2005/Russia | Case series, nonrandomized, open label | IT | Human Fetal Cells | Hemorrhagic (3 cases) in MCA and ischemic (7 cases) in MCA or MCA+ACA | 35–56 | 4 to 24 months (mean 12.1 months) | 10 (10 historical controls) | 1 (5 patients) or 2 (5 patients) infusions of 2×108 | Not specified | 6 months |
Kondziolka et al., 2005/United States | Phase II, randomized, single-blind | IC | NT2N cells | Ischemic (9 cases) or hemorrhagic (9 cases) involving basal ganglia | 40–70 | 1 to 5 years (mean 3.5 years) | 14 (4 controls without injection) | 5×106 (7 patients); 1×107 (7 patients) | Not specified | 18 to 29 months |
Savitz et al., 2005/United States | Phase I, nonrandomized, open label | IC | Fetal Porcine cells | Ischemic involving the striatum | 25–52 (mean 39.8) | 4 to 10 years (mean 4.9 years) | 5 (no controls) | Up to 5 injections of 107 | 10 μL/min, 106 cells/μL | 4 years |
Man et al., 2006/China | Case series, nonrandomized, open label | IV | Allogeneic UC-MNCs | Ischemic (6 cases) or hemorrhagic (4 cases) | 35–75 (mean 56) | 3 months to 7 years (mean 23.5 months) | 10 (no controls) | 6 infusions of≥1×108, 1 to 7 days apart | Not specified | 3 months |
Mendonca et al., 2006; Correa et al., 2007/Brazil | Case reports on phase I, nonrandomized, open label | IA | Autologous BM-MNCs | MCA ischemic stroke | 54 and 37 | 5 (1 patient) and 9 days (1 patient) | 2 (no controls) | 1×108 (1 patient) and 3×107 (1 patient) | 3 mL in 10 min (first patient) | 2–4 months |
Suarez-Monteagudo et al., 2009/Cuba | Case series, nonrandomized, open label | IC | Autologous BM-MNCs | Ischemic or hemorrhagic in thalamus, basal ganglia or cortex | 41–64 (mean 51.4) | 3 to 8 years (mean 5 years) | 5 (no controls) | 1.4×107to 5.5×107 (mean 3.4×107) | 8 seeds of 2.5 μL | 1 (4 cases) and 5 years (1 case) |
Lee et al., 2010 (cont. of Bang et al., 2005)/South Korea | Phase I/II, randomized, single-blind | IV | Autologous BM-MSCs | MCA ischemic stroke | Mean 64 | Injections 19 to 37 days (median 32.5 days) and 2 weeks later | 16 (36 controls without injection) | 5×107 (2 doses 2 weeks apart) | Not specified | 5 years |
Battistella et al., 2011; Rosado-de-Castro et al., 2013/Brazil | Phase I, nonrandomized, open label | IA or IV | Autologous BM-MNCs | MCA ischemic stroke | 24–68 (mean 58.5) | 19 to 89 days (mean 64.5) | 12 (no controls) | 1×108 to 5×108 (mean 3.1×108) | 10 mL in 10 min (1 mL/min) | 6 months |
Honmou et al., 2011/Japan | Phase I, nonrandomized, open label | IV | Autologous BM-MSCs | Ischemic gray matter, white matter and mixed lesions | 41–73 (mean 59.2) | 36 to 133 days (mean 68 days) | 12 (no controls) | 0.6×108 to 1.6×108 (mean 1.1×108) | In 30 min; volume not specified | 12 months |
Savitz et al., 2011/United States | Phase I, nonrandomized, open label | IV | Autologous BM-MNCs | MCA ischemic stroke | Mean 55 | 24 to 72 h | 10 (79 historical controls) | 7×108/kg to 1×109/kg (mean 9.6×108/kg) | In 30 min; volume not specified | 6 months |
Han et al., 2011/South Korea | Not specified | IT | Allogeneic UC-MSCs | Ischemic in pons, midbrain and right superior cerebellum | 17 | 35 days | 1 (no controls) | 3.6×107 | Not specified | 2 months |
Bhasin et al., 2011, 2012a, 2012b/India | Phase I, nonrandomized, single-blind (fMRI) | IV | Autologous BM-MSCs or BM-MNCs | MCA ischemic or hemorrhagic stroke | Mean 45 | mean 9.6 months | 20 (14 BM-MNC group; 6 BM-MSC group; 20 controls without injection) | 5×107 to 6×107 | 250 mL in 3 h (1.4 mL/min) | 6 months |
Friedrich et al., 2012/Brazil | Phase I/II, nonrandomized, single-blind (CT) | IA | Autologous BM-MNCs | MCA ischemic stroke | 30–78 (mean 63) | 3 to 10 days (mean 6 days) | 20 (no controls) | 5.1×107 to 6×108 (mean 2.2×108) | 15 mL in 30 min (0.5 mL/min) | 6 months |
England et al., 2012, United Kingdom | Subgroup of phase IIb, randomized, controlled trial with | IV | Autologous CD34+ PB-HPSCs | Ischemic stroke | Not specified for sub-group | 3 to 30 days | 8 (6 G-CSF group; 2 placebo group; no controls) | 2×107 to 4.3×108 | Not specified | 3 months |
Sharma et al., 2012/India | Not specified | IT | Autologous BM-MNCs | Left thalamic hemorrhagic stroke | 69 | 1 year | 1 (no controls) | 5×107 | Not specified | Not specified |
Moniche et al., 2012/Spain | Phase I/II, nonrandomized, single-blind | IA | Autologous BM-MNCs | MCA ischemic stroke | Mean 66.9 | 5 to 9 days (mean 6.4 days) | 10 (10 controls without injection) | mean 1.6×108 | 0.5 to 1 mL/min; duration not specified | 6 months |
Prasad et al., 2012/India | Phase I, nonrandomized, open label | IV | Autologous BM-MNCs | MCA or MCA+ACA ischemic stroke | 30–70 (mean 51.5) | 8 to 29 days (mean 17 days) | 11 (no controls) | 1.9×108 to 1.9×109 (mean 8×107) | In 5 min; volume not specified | 12 months |
Li et al., 2012/China | Phase I, nonrandomized, single-blind | IC | Autologous BM-MNCs | Basal ganglia hemorrhagic stroke | 39–74 (mean 56.3) | 5 to 7 days (mean 5.9 days) | 60 (40 controls with saline) | 2.5×108 to 2.3×109 (median 1.3×109) | 3.5 mL; duration not specified | 6 months |
Jiang et al., 2012/China | Phase I, non-randomized, open label | IA | Allogeneic UC-MSCs | MCA ischemic (3 cases) or hemorrhagic (1 case) stroke | 40–59 (mean 49) | 11 to 50 days (mean 25.5) | 4 (no controls) | 2×107 | 20 mL in 20 min (1 mL/min) | 6 months |
IC, intracerebral; IA, intra-arterial; IV, intravenous; IT, intrathecal; BM-MNCs, bone marrow mononuclear cells; BM-MSCs, bone marrow-derived mesenchymal stem cells; UCB-MNCs, umbilical cord blood mononuclear cells; UC-MSCs, umbilical cord-derived mesenchymal stem cells; MCA, middle cerebral artery; ACA, anterior cerebral artery; NT2N, human teratocarcinoma-derived neurons; PB-HSPCs, peripheral blood hematopoietic progenitor/stem cells.