Table 1.
Clinical trials of stem cell therapy in stroke patients
| 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 | |
aEquivalent to preclinical studies.
bUS Food and Drug Administration (FDA) regulation on cell therapy.
cClinical staging for cell lines by the International cellular medicine society (ICMS).
f/u follow-up, mRS modified Rankin Score, MSC mesenchymal stem cell, NIHSS National Institutes of Health Stroke Scale, PCR polymerase chain reaction.