Several studies have shown that mesenchymal stromal/stem cells (MSCs) exert their neuroprotective and neurorestorative efficacy via the secretion of neurotrophic factors. Based on these studies, many clinical trials using MSCs for the treatment of neurological disorders have been conducted, and results regarding their feasibility and efficacy have been reported.
Reference | Disease | Source | Number | Mean Age (Range), Year | Route of Administration | Number of Cells | Number of Treatments | Results | Adverse Events | |
---|---|---|---|---|---|---|---|---|---|---|
Trial | Control |
Reference | Disease | Source | Number | Mean Age (Range), Year | Route of Administration | Number of Cells | Number of Treatments |
---|
Reference | Disease | Source | Results | Number | Mean Age (Range), Year | Route of Administration | Number of Cells | Adverse Events | |
---|---|---|---|---|---|---|---|---|---|
Number of Treatments | Results | Adverse Events |
Reference | Disease | Source | Number | Mean Age (Range), Year | Route of Administration | Number of Cells | Number of Treatments | Results | Adverse Events | ||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Trial | Control | ||||||||||||
Trial | Control | ||||||||||||
Trial | Control | ||||||||||||
Chung et al. [48][19] | Ischemic stroke (Phase 3) |
BM | 39 | ||||||||||
Gu et al. | 15 | [67] | 68 | (28–83) | IV | ||||||||
Xiao et al. [56][27[ | 1 × 10 | 6 | /kg | 1 | ] | 38 | |||||||
Berry et al. [71][ | Spinal cord injury (Phase 1) | Lower extremity motor functional recovery | UCB | 42]2 | 0 | ] | ALS28, 30 | Transplantation into the lesion with collagen scaffolds | 4 × 107 cells | 1after 3 months | Motor functional recovery after 3, 6, 12 months No |
||
Sensory functional recovery after 2, 4, 12 months | Cerebral palsy | No | (Phase 1/2) | UC | 19 | 20 |
4.29 | IV | (Phase 2)4.5–5.5 × 10 | BM-NTF | 367 | 12 cells at 7-day intervals |
4 |
Mazzini et al. | |||||||||||||
[ | |||||||||||||
78 | |||||||||||||
] | |||||||||||||
[49] | ALS (Phase 1) | BM | 19 | 0 | 20–75 | Direct injection into spinal cord | 7–152 × 106 cells | 1 | No long-term adverse effect after nearly 9 years | No |
Reference | Disease | Source | Number | Mean Age (Range), Year | Route of Administration | Number of Cells | Number of Treatments | Results | Adverse Events | |
---|---|---|---|---|---|---|---|---|---|---|
Trial | Control | |||||||||
Petrou et al. [79][50] | 51.1 | Multiple sclerosis (Phase 2) | (26–71) | BM | 16, 16 |
16IM + IT | 47.6 (37.9–57.3) |
IT orIM: 48 × 106 cells IT: 125 × 106 cells | ||
IV | ||||||||||
1–2 × 10 | ||||||||||
6 | ||||||||||
/kg | 1 | Improvement in the imaging studies after 6 months | No | |||||||
Macular rash, self-limiting infections | ||||||||||
Reference | Disease | Source | Number | Mean Age (Range), Year | Route of Administration | Number of Cells | Number of Treatments | Results | Adverse Events |
---|
Reference | Disease | Source | Number | Mean Age (Range), Year | Route of Administration | Number of Cells | Number of Treatments | Results | Adverse Events | ||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Trial | Control | ||||||||||||||||||||||||||||
Gross motor and comprehensive functional recovery and improvement in the ADL after 3, 6, 12 months | No | ||||||||||||||||||||||||||||
Trial | Control | ||||||||||||||||||||||||||||
1 | Improvement in the rate of disease | progression after 6 months | Headache, fever, back pain, injection site bruising | ||||||||||||||||||||||||||
IV | 1 × 10 | 6 | /kg at 6-month intervals | ||||||||||||||||||||||||||
Canesi et al. [89][60] | Progressive supranuclear palsy (Phase 1) | 1 or 2 | BM | ||||||||||||||||||||||||||
Wang et al. [91][ | 5 | 0 | 60–68 | 62] | Traumatic brain injury (Phase 2) |
UCIA (intra-arterial) via catheterization | 1.7 (1.2–2.0) × 106/kg | 1 | 20 | 20 | 27.5 ± 9.4Clinical stabilization for at least 6 months during the one-year follow-up | 28.6 ± 10.1 |
IT | 6.0 × 107 cellsImprovement in the course of the disease and comprehensive functional recovery after 3, 6, 12 months. |
4IT is more efficacious than IV | Comprehensive functional recovery and improvement in the ADLNo | Transient left hemiparesis | after 6 months | |||||||||||
Bhasin et al. [49][20] | Ischemic stroke | BM | 6 | Syková et al. [6 | 73][42.8 (20–60) |
IV | 5–6 × 107 cells | 1 | Improvement in the activities of daily living (ADL) after 156 and 208 weeks | No | |||||||||||||||||||
Ahn et al. [68][39] | 44Intraventricular hemorrhage (Phase 1) |
] | ALS (Phase 1/2)UCB |
BM | 26 | 0 | |||||||||||||||||||||||
Fernández et al. | |||||||||||||||||||||||||||||
Li et al. | |||||||||||||||||||||||||||||
Mild dizziness, headache | 9 | [81 | 0 | ][52] | Carstens et al. [90][6111.6 51.2 (33–64) |
] | Parkinson’s disease (Case studies) |
AD MSC-derived stromal vascular fraction | 2IT | Multiple sclerosis (phase 1/2)(7–15)15 ± 4.5 × 106 cells |
1 | Slowing down of the diseaseprogression after 3, 6, 9 months | ADHeadache | ||||||||||||||||
10, | 9 | (days) | 11 | 44.8 47.8 46.3 |
0IV | 72, 50 | Facial and nasal transplantation1 × 10 | ||||||||||||||||||||||
Tian et al. [92][63] | 6 | /kg | or | 4 × 10 | 6/kg | 6.0 × 101 | Partial efficacy in the imaging studies and evoked potentials after 12 months | 7urinary infection | cells | 1 | Subjective functional recovery after 2 weeks and up to 5 years | Traumatic brain injuryNo | BM | 97 | 0 | - | IT | 3.0–5.0 × 106 cells | 1 | Improvement of consciousness and motor function after 14 days | No | NSPC 6 × 106 cells at one-week interval | 4 | Staff et al. [75][46] |
ALS (Phase 1) |
AD | 27 | ||
Riordan et al. [80][51] | 0 | Multiple sclerosis (phase 1/2) | or | UC | 2036–75 | IT | 1 × 107, 5 × 101 + 3 | Improvement in the neurological functions and ADL after 3, 12, 24 months | Fever, dizziness | ||||||||||||||||||||
0 | 7 | 41.15 | , 5 × 10 | IV | 7 | × 2, 1 × 10 | 20 × 1068, 1 × 108 × 2 | 1 or 2 | cells at 1–4-day intervalsOnly safety assessment | Temporary back and leg pain in the highest dose | Jiang et al. [53] | ||||||||||||||||||
7 | Comprehensive functional recovery after one month | Headache, fatigue | [24] | Petrou et al. [72][43Ischemic and hemorrhagic stroke | UC | 4 | ] | ALS (Phase 1/2) |
BM-NTF | 26 | 0 | 48.1, 50.8 | |||||||||||||||||
Harris et al. [82][53] | Multiple sclerosis (Phase 1) |
BM MSC -derived neural progenitors | 200 | 40–59 | IA (intra-arterial) via catheterization | 2 × 107 cells | 1 | Motor functional recovery and improvement in the ADL after 3 and 6 months | No | ||||||||||||||||||||
Bhasin et al. [50][21] | Ischemic stroke | BM | 20 MSC6 MNC14 |
20 | 45.1 | IV | 5–6 × 107 cells | 1 | Improvement in the ADL after 8 and 24 weeks | ||||||||||||||||||||
Vaquero et al. [54][25] | Spinal cord injury (Phase 2) |
BM | 11 | 0 | 44.91 (28–62) |
IT | Intraventricular100 × 106 cells at 3 months interval | 5 × 103 | 6/kg or 1 × 107/kgMotor, sensory and bladder–bowel functional recovery after 4, 7, 10 months |
No | 1 | Only safety assessment | No | Qiao et al. [52][23] | Ischemic stroke (Phase 1/2) |
UC | 6 | ||||||||||||
Vaquero et al. | 0 | [58][ | 56.17 | (3–85) | IVIV + IC | 29]IV:MSC 0.5 × 10 | Post-traumatic syringomyelia30] | ||||||||||||||||||||||
Huang et al. [65][36] | (Phase 2) |
Cerebral palsy (Phase 1/2) | 6 | /kg | IC:MSC 5 × 10 | 6 cells | BM | 6 | 0 | 39 (30–50) |
UCB | 27 | 27Direct injection into the lesion |
7.4 300 × 106 cells |
1 | (3–12)Achieving reduction of syrinx and valiable clinical improvements after 6 months | No | ||||||||||||
IV | 5 × 10 | 7 | cells at 7-day intervals | 4 | Gross motor and comprehensive functional recovery after 3, 6, 12, 24 months | No | Vaquero et al. [59][ | Spinal cord injury (Phase 2) |
0(23–65) | IM IT IM + IT |
27–65IM: 2.4–4.8 × 107 cells IT: 1.0–2.0 × 10 |
IT | 5.3–10 × 1066 /kg | 1 | Improvement in the rate of disease progression after 6 months | cells at 3-month intervals | 3Fever, |
Motor, bladder and comprehensive functional recovery after 3 monthsvomiting, headache |
No | ||||||||||
headache, fever | Rushkevich et al. [76][47] | ALS | BM-MSC and neural induced MSC | 10 | 15 | 54.5, 55.0 | |||||||||||||||||||||||
Dahbour et al. [ | Honmou et al. [51][22] | Ischemic stroke (Phase 1) |
BM | 12 | 0 | 59.2 (41–73) |
IV | 0.6–1.8 × 108 cells | 1 | Incremental daily rate of change in the disability scales during 12 months |
Fever, nausea, itching |
BM | |||||||||||||||||||||||
10 | |||||||||||||||||||||||
0 | 42.2 | (34–59) | |||||||||||||||||||||
Liu et al. [ | IT | 66][37] | Cerebral palsy (Phase 1/2) |
BM | MSC 33 MNC34 |
35 | 7–132 (months) |
IT30 × 106 cells at 3-months interval | 4 | 1 × 106/kg at 3–4-day intervalsMotor, sensory and bladder–bowel functional recovery after 3, 6, 9, 12 months | 4Headache, puncture pain |
||||||||||||
Motor functional recovery after 12 months | No | Satti et al. [60][31] | |||||||||||||||||||||
Wang et al. [69][ | Spinal cord injury (Phase 1) |
BM | 9 | 0 | 31.6 (24–38) |
IT | 1.2 × 106/kg at 4 weeks interval | 2 or 3 | 40Only safety assessment | No | |||||||||||||
] | 83Cerebral palsy (Phase 4) |
UC | 16 (8 twins) | 0 | ][546.29 (3–12) |
IT | ] (37–66)1–2 × 106 cells at 3–5-day intervals |
IV + IT | 0.5–1.5 × 10 | Multiple sclerosis (Phase 1/2)6/kg4 |
5.0–9.7 × 10Motor functional recovery after 1 and 6 months |
6No | cells at 5–7-month intervals |
BM1 or 2 | Slowing down of the disease progression after 12 months |
Fever, headache | |||||||
MSC-CM | 10 | 0 | 34.9 | (18–54) | IT | 93–168 × 106 cells CM:13–20 mL at 1-month intervals |
1 + 1 | Comprehensive functional recovery after 12 months | Pain, headache, fever | Oh et al. [57][28] | Oh et al. [74][45Spinal cord injury (Phase 3) |
BM | ]16 | 0 | 40.9 (18–65) |
Direct injection into the lesion + IT | |||||||
Wang X et al. [70][41] | 1.6 × 10 | 7 | Cerebral palsy | cells | BM | 463.2 × 107 cells | 1 | ALS 0 |
(Phase 1)6–180 (months) |
BMIT Intra-Parenchymal |
2 × 107 | 8 cells | |||||||||||
Llufriu et al. [ | 0 | 84][55 | 45.7 | (29–62) | IT | ]1 × 10 | Very weak therapeutic efficacy after 6 months | 4 × 107 cells at 5-day intervals |
2 + 1Sensory deterioration, muscle rigidity, tingling sense | ||||||||||||||
6 | /kg at | 26-day intervals | or | 2 | Multiple sclerosis (Phase 2) |
BM | 9 | 0 | 36.8 (23–48)4 |
Gross motor functional recovery after 1, 6, 18 months | No | No efficacy after 6 months | Fever, pain, headache | Hur et al. [55][26] | Spinal cord injury (Phase 1) |
AD | 14 | 0 | 41.9 (20–66) |
IT | |||
Kim et al. [77][48] | 3 × 10 | ALS | 7 | BM | 37 | 0 | at 1-month interval | [3 | 85Motor and sensory functional recovery after 8 months | 52.7, 48.8 | ][56IT | 1 × 106/kg atNausea, vomit, headache | |||||||||||
one-month intervals | ] | Multiple sclerosis | UC | 13 | 10 | 2 | Trophic factors associated with a positive response to treat | No | |||||||||||||||
41.7, 39.4 | IV | 4 × 10 | 6 | cells/kg at 2-week intervals | 3 | Improvement in the overall symptoms and | fewer incidences of relapse during 12 months | No | Mendonça et al. [61][32] | ||||||||||||||
Bonab et al. [86][57 | Spinal cord injury (Phase 1) |
BM | 14 | 0 | ] | Multiple sclerosis (Phase 2)35.7 |
BM (23–61) |
Direct injection into the lesion | 5 × 106 cells/cm3 per lesion volume | 1 | Motor, sensory, and bladder–bowel functional recovery after 6 months | 25Low-intensity pain at the incision site, cerebrospinal fluid leak |
|||||||||||
0 | 34.7 | (23–50) | IT | 2.95 × 10 | 7 | cells | 1 | Improvement or stabilization in the course of the disease during 12 months |
Fever, nausea, weakness in the lower limbs, headache | Cheng et al. [62][33] | |||||||||||||
Lee et al. [87][58 | Spinal cord injury (Phase 2) |
UC | ]10 | 34 | Multiple sclerosis 35.3 (19–57) |
Direct injection into the lesion | 2 × 107 cells at 10 days interval | 2 | Motor, sensory, and bladder functional recovery after 6 months Superior efficacy than that of rehabilitation therapy |
Radiating neuralgia | |||||||||||||
(Phase 2) | BM | 16 | 17 | 56.1, 55.8 | IA (intra-arterial) + IV | IA: 4 × 10 | 7 cells IV: 4 × 107 cells at 30-day intervals |
1 + 3 | Efficacy in preventing the progression of neurological deficits during 12 months | Small ischemic lesions |
Dai et al. [63][34] | ||||||||||||
Connick et al. [88][59] | Spinal cord injury (Phase 1/2) |
Multiple sclerosis BM |
20 | 20 | 22–54 | Direct injection into the lesion | 20 × 106 cells | 1 | Motor, sensory, and bladder functional recovery after 6 months | Fever, headache, pain | |||||||||||||
(Phase 2) | BM | 10 | 0 | 48.8 | (40–53) |
IV | 1.6 × 106 | Karamouzian et al. [64][35] | Spinal cord injury (Phase 1/2) |
BM | 11 | 20 | 33.2 (23–48) |
IT | 0.7–1.2 × 106 cells | 1 | Possible efficacy in the motor and sensory function | No |
/kg |
1 |
Visual functional recovery after 10 months |