Table 2.
Clinical studies using bone marrow stromal stem cells for regenerative medicine.
| Musculoskeletal Conditions | |||||||
|---|---|---|---|---|---|---|---|
| Reference | No. of patients | Study design | Indication | Source | Administration | Outcome | Follow-up |
| Kitoh et al. 2007 [25] | 46 | Case control | Distraction osteogenesis of the long bones | Autologous | Combination of SSCs and PRP injected into the distracted callus | Reduced treatment period and associated complications, accelerated new bone formation | NK |
| Horwitz et al. 2002 [27] | 6 | Case series | Osteogenesis imperfecta | Allogeneic | Infusion | No toxicity, engraftment in bone, marrow stroma, and skin, acceleration of growth | 3–6 months |
| Cahill et al. 2007 [28] | 1 | Case report | Infantile hypophosphatasia | Bone fragments from donor father and cultured osteoblasts | ip, sc, iv infusion | Improved skeletal mineralization, no premature loss of deciduous teeth | 7 years |
| Wong et al. 2013 [42] | 56 | Phase II RCT | Cartilage repair (knees) | Autologous | Intra-articular injection | Improved clinical and radiologic outcomes | 2 years |
| Cardiovascular Diseases | |||||||
| Rodrigo et el. 2013 [45] | 9 | Case series | Acute MI | Autologous | Intramyocardial injection | No adverse events, improvement of LV function similar to percutaneous coronary intervention | 5 years |
| Lee et al. 2014 [46] | 58 | Phase I-II RCT | Acute MI | Autologous | Intracoronary injection | No significant adverse events, modest improvement in LV ejection fraction | 6 months |
| Chen et al. 2004 [47] | 69 | Phase II RCT | Acute MI | Autologous | Intracoronary injection | Safe, improved LV function | 6 months |
| Katritsis et al. 2005 [48] | 22 | Cohort study | Recent and old anteroseptal MIs | Autologous | Intracoronary infusion | Safe, improved myocardial contractility | 4 months |
| Hare et al. 2009 [49] | 53 | Phase I-II RCT | Acute MI | Allogeneic (Prochymal) | Intravenous | Safe, increased LV ejection fraction and led to reverse remodeling | 6 months |
| Williams et al. 2011 [50] | 8 | Case series | Ischemic cardiomyopathy | Autologous | Intramyocardial injection | Improved regional contractility of a chronic myocardial scar | 1 year |
| Mathiasen et al. 2012 [51] | 60 | Phase II RCT | Chronic ischemic heart failure | Autologous | Intramyocardial injection | Confirms the results from previous openlabeled clinical trials | 1 year |
| Ascheim et al. 2014 [52] | 30 | Phase I-II RCT | End-stage heart failure | Allogeneic | Intramyocardial injection | Safe, increased successful temporary wean off device | 12 months or until cardiac transplant |
| Heldman et al. 2014 [53] | 65 | Phase I-II RCT | Ischemic cardiomyopathy | Autologous | Transendocardial injection | No treatment-emergent serious adverse events, improved regional myocardial function, reduced infarct size | 1 year |
| Karantalis et al. 2014 [54] | 6 | Case series | Chronic ischemic left ventricular dysfunction secondary to MI | Autologous | Transepicardial delivery | Increased LV ejection fraction and decreased scar mass | 18 months |
| Hare et al. 2012 [55] | 31 | Phase I-II randomized comparison | Ischemic cardiomyopathy | Autologous and allogeneic | Transendocardial injection | Both were safe and improved patient functional capacity, quality of life, and ventricular remodeling | 13 months |
| Chin et al. 2011 [57] | 10 | Case series | Severe dilated cardiomyopathy (ischemic and non-ischemic) | Autologous | Intramyocardial and intracoronary injection | Safe, improvement in left ventricular parameters, scar reduction | 1 year |
| Mushtaq et al. 2014 [58] | 36 | Phase I-II randomized pilot study | Non-ischemic dilated cardiomyopathy | Autologous and allogeneic | Transendocardial injection | Designed to compare allogeneic vs. autologous mesenchymal stem cell therapy | 1 year |
| Mathiasen et al. 2013 [59] | 31 | Non-randomized prospective phase I-II clinical trial | Severe stable coronary artery disease and refractory angina | Autologous | Intramyocardial injection | Clinical improvements in exercise time, angina class, weekly number of angina attacks and use of nitroglycerine, reduced hospital admissions, long term safety | 3 years |
| Henry et al. 2014 [56] | 61 | Phase II RCT | Ischemic and non-ischemic cardiomyopathy | Autologous | Minithoracotomy catheter injection, intramyocardial injection | Ixmyelocel-T intramyocardial injection reduced major adverse cardiovascular events only in patients with ischemic dilated cardiomyopathy | 1 year |
| Liver and Kidney Diseases | |||||||
| Amer et al. 2011 [61] | 40 | Phase I-II RCT | End-stage liver failure due to hepatitis C | Autologous | Intrasplenic and intrahepatic administration | Safety, short-term efficacy, no difference between intrasplenic and intrahepatic groups | 6 months |
| El-Ansary et al. 2012 [62] | 25 | Phase II clinical trial | Hepatitis C induced liver cirrhosis | Autologous | iv infusion | Partial improvement of liver function tests (elevation of prothrombin and serum albumin levels, decline of elevated bilirubin) | 6 months |
| Jang et al. 2014 [63] | 12 | Phase II clinical trial | Alcoholic cirrhosis | Autologous | Injection through the hepatic artery | No side effects, histological improvement of hepatic fibrosis | 12 weeks |
| El-Ansary et al. 2012 [65] | 30 | Case series | Chronic kidney disease | Autologous | Intravenous infusion | Reduction of serum creatinine, elevation of creatinine clearance levels | 6 months |
| Diabetes | |||||||
| Carlsson et al. 2015 [70] | 20 | Phase I-II RCT | Type 1 diabetes | Autologous | Intravenous infusion | No side effects, preserved β-cell function | 1 year |
| Bhansali et al. 2014 [71] | 10 | Phase I-II RCT | Type 2 diabetes | Autologous | Injection into the superior pancreaticoduodenal artery | Increase in glucagon-stimulated C-peptide, decrease in insulin requirement | 1 year |
| Lu et al. 2011 [73] | 41 | Phase I-II RCT | Diabetic critical limb ischemia and foot ulcer | Autologous | Intramuscular injection | Well tolerated, increased lower limb perfusion and foot ulcer healing | 24 weeks |
| Neurological Diseases | |||||||
| Slavin et al. 2008 [77] | 12 | Case series | MS, ALS | Autologous | Intrathecal and iv injection | Safe procedure, no major risks | 1 year |
| Oh et al. 2015 [78] | 7 | Phase I trial | ALS | Autologous | Intrathecal injection | No serious adverse events of repeated intrathecal injections of autologous SSCs | 1 year |
| Wang et al. 2013 [79] | 52 | Open-labeled, self-controlled trial | Cerebral palsy | Autologous | Intrathecal or intraparenchymal infusion | No side effects, improved motor function | 18 months |
| Chen et al. 2013 [80] | 60 | Phase I-II controlled clinical trial | Cerebral palsy | Autologous | Injection into the subarachnoid cavity | No adverse events, increase in motor function | 6 months |
| Venkataramana et al. 2010 [81] | 7 | Case series | Parkinson’s disease | Autologous | Transplantaion into the sublateral ventricular zone by stereotaxic surgery | No serious adverse events, subjective improvement in facial expression, gait, and freezing episodes | 10–36 months |
| Pal et al. 2009 [82] | 30 | Case series | Spinal cord injury/paraplegia | Autologous | Lumbar puncture | No serious adverse events | 1–3 years |
| Zhang et al. 2008 [83] | 7 | Case series | Traumatic brain injury | Autologous | Direct application during cranial surgery, iv infusion | No toxicity, significantly improved neurologic function | 6 months |
HA: Hydroxyapatite; β-TCP: Beta-tricalcium phosphate; iv: Intravenous; ip: Intraperitoneally; sc: Subcutaneously; MI: Myocardial infarction; LV: Left ventricular; ALS: Amyotrophic lateral sclerosis; MS: Multiple sclerosis; GVHD: Graft vs. host disease; CR: Complete response; PR: Partial response; MR: Mixed response; GI: Gastrointestinal; SLE: Systemic lupous erythematosus NK: Not known