Factors | Neural stem/progenitor cells | Bone marrow mononuclear cells | Mesenchymal stem cells | ||||
---|---|---|---|---|---|---|---|
Lead author, year, reference | Savitz, 2005 [2] | Savitz, 2011 [4] | Friedrich, 2012 [5] | Bang, 2005 [6] | Lee, 2010 [7] (STARTING trial) | Honmou, 2011 [8] | Bhasin, 2011 [9] |
Study design | No control group | No control group | No control group | Control, n = 25 | Control, n = 36 | No control group | Control, n = 6 |
Treatment, N = 5 | Treatment, N = 10 | Treatment, N = 20, | Treatment, n = 5 | Treatment, n = 16 | Treatment, n = 12 | Treatment, n = 6 | |
4 years f/u | 6 months f/u | 6 months f/u | 1 year f/u | 5 years f/u | 1 year f/u | 24 weeks | |
Brain infarct | Chronic basal ganglia infarct | Acute (24 to 72 h), large hemispheric | Acute (3 to 7 days), non-lacunar | Subacute, large cortical | Subacute, large cortical | Chronic (36 to 133 days), large cortical | Chronic (3 months to 1 year) |
Cells used | Neural progenitor cells from primordial porcine striatum | Autologous bone marrow mononuclear cells | Autologous bone-marrow-derived mesenchymal stem cells | ||||
Cell dose | 2 × 107 cellsa | 1 × 106 cells/kga | 2.2 × 108 cellsa | 1 × 108 cellsa | 1 × 108 cellsa | 1 × 108 cellsa | 5 to 6 × 107 cellsa |
Manipulation | Fetal porcine striatum was washed, triturated, and dissociated to yield cell suspensions | Isolation using human albumin-containing normal saline | Ex vivo culture expansion using fetal bovine serum | Ex vivo culture expansion using autologous serum | Ex vivo culture expansion using animal serum-free media (Stem Pro SFM) | ||
FDAb | More than minimal manipulation | Minimal manipulation | More than minimal manipulation | ||||
ICMSc | Early investigational cell line | Clinical grade | Clinical grade | Clinical grade | Clinical grade | ||
Mode of application | Intralesional | Intravenous | Intraarterial | Intravenous | |||
Presumed mechanisms | Cell replacement and trophic support | Trophic support | Trophic support | ||||
Efficacy | Not available | mRS 1 shift vs historical control | Good outcome (mRS 0 to 2) in 40% | Barthel index improved at 3 months | Proportion of mRS 0 to 3 increased in MSC but not control group | Improve in daily rate of NIHSS changes | Modest increase in Fugl-Meyer and mRS |
Adverse effect | 1 seizure, 1 worsening of weakness | None | None | None | None | None | None |
Safety test | Cell viability PCR testing for porcine endogenous retrovirus | Cell viability MSC surface markers; bacteria, fungi, mycoplasma culture. | Cell viability | Cell viability MSC surface markers; bacteria, fungi, viral and mycoplasma culture. | Cell viability, MSC surface markers; bacteria, syphilis, fungi, viral, mycoplasma, endotoxin level. | Cell viability; mycoplasma, endotoxin level |