TABLE 3.
Summary of the regenerative role of MSCs in clinical trials
| Disease | Patient profile | MSC Source | Dose (×106) | Administration | Outcome | Ref [MFR ref] |
|---|---|---|---|---|---|---|
| Cardiovascular disorders | ||||||
| Ac myocardial infarction | n = 27 | Auto BM-MSC | Low = 50 (n = 6), high = 700 (n = 21) | Intracoronary | Dose did not affect outcome. Marked improvement in LVEF in patients with low pCO2 and HCO3. | 80 [80] |
| Ac myocardial infarction | n = 53 (MSC n = 39, Ctrl n = 21). | Allo BM-MSC | 0.5, 1.6, 5/kg | IV | GSS and EF significantly better (p = 0.027) in MSC versus Ctrl, with an average AE rate of 5.3 and 7, respectively. | 81 [prochymal] |
| Ac myocardial infarction | AMI with PCI (n = 16) | Auto BM-MSC | 12.2 ± 1.77 (grp-l), 13.2 ± 1.76 (grp-lI) | LAD Group I (n = 8), RCA Group II (n = 8) | Symptomatic improvement at t = 6 months, with MSC infusion. No patient died, was readmitted, or had another MI. No angiographic in-stent restenosis detected in either group. | 82 [82] |
| Ac myocardial infarction | AMI with PCI (MSC n = 35; Ctrl n = 35) | Auto BM-MSC | 8 × 103−1 × 104/mL | Intracoronary | Significant improvement (p < 0.05) in cardiac function in MSC versus Ctrl at t = 3 months and t = 6 months. | 83 [5] |
| Myocardial infarction (old) | MSC n = 8; Ctrl n = 8 | Auto BM-MSC | 5.55 (2.1–9.1) | Injected at CABG or PCI | Significant improvement in NYHA class (p < 0.000), SPECT scan (p < 0.002), and LVEF (<0.005) in MSC versus Ctrl. | 84 [84] |
| Myocardial infarction (old and recent) | MSC n = 11; Ctrl n = 11 | Auto BM-MSC and EPCs | 1–2 | Intracoronary | Intracoronary use of MSCs is feasible, safe, and helps in local regeneration of myocardial tissue early or late following MI. | 85 [85] |
| Refractory angina | n = 31 | Auto BM-MSC | NA | Intramyocardial | All showed significant improvement (p < 0.001) in LVEF and exercise tolerance from baseline level. | 86 [86] |
| Ischemic cardiomyopathy | LV dysfunction with remote Ml (n = 8) | Auto BM-MNC (n = 4), BM-MSC (n = 4) | 200 | TEC injection | MNCs and MSCs help to reverse remodeling of chr, myocardial scar. Significant declines in systolic and diastolic volumes, obscuring → EF Chamber size, MI size, or regional function more likely to improve with treatment. | 87 [87] |
| Dilated cardiomyopathy | n = 40 (PBEP n = 11, BM-MNCs n =29) | Auto-PBEP and BM-MNCs | 5 mL (100 to 1000 cells/mL) | EC n = 9, IC n = 25, IP n = 6 | Significant improvement in EF (25%) at t = 6 months. Repeated stem cell infusion required for sustained improvement. | 88 [88] |
| Ischemic cardiomyopathy | MSC n = 22; Ctrl n = 23 | Auto BM-MSCs | NA | Intracoronary | Significant improvement in exercise tolerance, ↓ reversible defects (p < 0.05) at t = 12 months in MSCs versus baseline and Ctrl. | 89 [89] |
| Dilated cardiomyopathy | MSC n = 12; Ctrl n = 12 | Auto BM-MSCs | NA | Intracoronary | Significant ↓ in plasma BNP levels (p < 0.05) and improvement in 6-minute walk test in MSC versus baseline and Ctrl. | 90 [90] |
| Limb or skin disorders | ||||||
| Type 2 diabetes with limb ischemia | n = 41 (82 limbs): MSC n = 20, MNC n = 21, Ctrl n = 41 | Auto BM-MSCs and MNCs | MSCs, 930 ± 110; MNCs, 960 ± 110 | Intramuscular injection | Marked improvement in rest pain (p< 0.05) and pain free walking in both groups from baseline. MSC Group showed better (p < 0.02) ulcer healing and collateral formation than MNC Group. | 95 [95] |
| Type 2 diabetes with limb ischemia | Limb ischemia (n = 10) | Auto BM-MSCs and MNCs | MSCs and MNCs, 30 | Intramuscular injection | Marked improvement in rest pain (p< 0.05) and pain-free walking from baseline. Better (p < 0.02) ulcer healing and collateral formation. | 96 [96] |
| Cutaneous wound healing | Acute (n = 5); chronic (n = 8) | Auto BM-MSCs | 2/cm2 wound surface area | LA, 4× fibrin polymer spray | All acute (skin cancer surgery) wounds showed complete recovery at 6 weeks. Only three of six chronic wounds showed complete closure, | 98 [98] |
| Nonhealing ulcers (chronic) | BGD (MSC = 9, Ctrl = 9), DM (MSC = 3, Ctrl = 3) | Auto BM-MSCs | 40–50 (>106 cells/cm2 of ulcer) | Intramuscular injection | Marked decrease in ulcer size (p < 0.001) and improvement in pain free walking (p <0.001) in MSC versus Ctrl. | 97 [97] |
| Hepatic disorders | ||||||
| Decompensated liver cirrhosis | Chr-HBV (MSC n = 30, Ctrl n = 15) | UC-MSCs | 0.5 | IV | Significant Improvement liver function and ↓ in ascites vol, for MSC versus Ctrl (p < 0.05). | 91 [108] |
| End-stage liver cell failure | Chr-HCV (MSC n = 20, Ctrl n = 20) | Auto BM-MSCs | 20 hep-lineage (total 200 MNCs) | IS n = 10, IH n = 10 | Improved child score, MELD score, fatigue scale, and ↓ ascites In vol, in MSC versus Ctrl, Route of Infusion not related to outcome. | 92 [92] |
| 4 HBV, 1HCV, 1 alcoholic, 2 crypto LF | Auto BM-MSCs | 30–50 | Peripheral or portal vein | MELD score showed marked improvement (p <0.05) in liver function versus baseline. | 93 [93] | |
| Decompensated liver cirrhosis | n = 4 | Auto BM-MSCs | 31.73 | Peripheral vein | 2/4 patients showed improvement In MELD score >with an overall ↑ QOL in all. | 94 [109] |
| Neurologic disorders | ||||||
| Ischemic stroke | n = 12 | Auto BM-MSCs | 0.6–1.6 | IV, 36–133 days after stroke | Marked Improvement (p< 0.001) In NIHSS change. Mean lesion volume ↓ >20% at 1 week after Infusion. | 99 [110] |
| Ischemic stroke | MSC n = 16, Ctrl n = 36 | Auto BM-MSCs | 50 (2 doses) | IV, 2 weeks apart | MSC group showed clinical Improvement (MRS score p < 0.05) versus Ctrl. Death in 25% of patients In MSC grp and 58.3% In Ctrl at follow-up. | 100 [100] |
| Parkinson’s disease | n =7 (MDD 14.7 ±7.56 years) | Auto BM-MSCs | 1 /kg | Stereotaxic lat, ventrlc, zone | 37 patients with Improved UPDRS. 22.9 and 38% Increase in mean “off” and “on” score versus baseline. Marked ↓ in dose noted in 2. | 111 [111] |
| Spinal cord injury | n = 30 (cervical or thoracic levels) | Auto BM-MSCs | 1 /kg | Lumbar puncture | Auto BM-MSCs are safe and feasible in spinal cord Injury patients. | 102 [102] |
| Ischemic stroke | n = 30 (MSC n = 5, Ctrl | Auto BM-MSCs | 50 (2 doses) | IV, 2 weeks apart | Barthel index in MSC grp better than Ctrl at t = 3, 6, and 12 months In (p = 0.011,0.017, 0.115) and MRS score (p = 0.076, 0.171, 0.286) | 101 [101] |
| Bone and cartilage disorders | ||||||
| Osteoarthritis (knee) | n = 25) n = 4 | Auto BM-MSCs | 8–9 | Intraarticular | Subjective clinical Improvement. No objective evidence of cartilage repair on X-ray. | 103 [103] |
| Osteoarthritis (AVN-F head) | 16 hips; A-Core, n = 8, B-MSC+ Core, n = 8 | Auto BM-MSCs | Not specified | Injected Into femur head | Marked difference in necrosis area of femoral head between group A and B at 12 months (p < 0.05). | 104 [104] |
| Osteoarthritis (knee) | n = 41 | Auto BM-MSCs | 5/mL | Artic, cartilage collagen sheet. | Primarily safety and feasibility study. | 105 [105] |
| Osteoarthritis (knee) | n = 1 | Auto BM-MSCs | 22.4 | Intraarticular | Significant cartilage and menlscal growth on MRI, ↑ In range of motion, ↓ in VAS pain scores. | 112 [112] |
| IOOD | n = 6 (dental implant placement) | Auto BM-MSCs | 400/cc scaffold | Implantation through scaffold | Viable bone substitute leading to bone formation In mice after SC implant. Same construct failed to form bone In IOOD patients. | 106 [106] |
| Miscellaneous | ||||||
| MLD and MPS-IH | MPS-IH (n = 5) MLD (n = 6; post-BMT) | Allo BM-MSCs (ID sib) | 2–10/kg | IV | No clinical Improvement in mental or physical development after MSC infusion, except ↑ in conduction velocity In MLD patients. | 107 [107] |
Ac. = acute; AE = adverse event; Allo = allogeneic; AMI = acute myocardial infarction; Auto = autologous; AWMI = anterior wall myocardial Infarction; BGD = Berger’s disease; CABG = coronary artery bypass graft; CAD = coronary artery disease; Chr, = chronic; Ctrl = control group; DM = diabetes mellitus; EC = eplcardial; grp = group; GSS = global symptom score; 1C = intracoronary; IH = Intrahepatlc; IOOD = intraoral osseous defect; IP = Intrapulmonary; IS = Intrasplenlc; LVEF = left ventricular ejection fraction; MELD = model for end-stage liver disease; MFR ref = MSC manufacturing protocol designed previously and followed in this study; MRS = modified Rankin score; NIHSS = National Institute of Health Stroke Scale; PBEP = peripheral blood endothelial progenitors; PCI = percutaneous coronary implant; QOL = quality of life; TEC = transendocardial; UC-MSC = umbilical cord-derived mesenchymal stem cells, Adverse events—Nil.