From: Mesenchymal stem cells (MSCs) as skeletal therapeutics–an update
References | Sample size | Cell type | Delivery route | Treatment outcomes |
---|---|---|---|---|
Osteogenesis Imperfecta | ||||
Horwitz et al., 2001 [67] | 3 | 5.5-6.2 × 108 cells per Kg, Allogeneic bone marrow stromal cells (MSCs) | Transplantation | Total body bone mineral content improved from 45 % to 77 % above baseline. Growth velocity improved. The rate of fractures reduced as documented by radiographs. |
Horwitz et al., 2002 [68] | 6 | 1-5 × 106 cells per Kg, MSCs transduced with retroviruses | Intravenous infusions, two doses with 8–21 days apart | Patients experienced significant improvement in growth velocity without concomitant increase in bone mineral content |
Le Blanc et al., 2005 [69] | Prenatal female fetus | 6.5 × 106, HLA mismatched fetal MSCs | Intra-uterine injection | X-ray absorptiometry showed 48 % skeletal mineralization compared to age matched counterpart |
Götherström et al., 2014 [70] | Female fetus with type IV OI | 30 × 106 cells per kg followed by postnatal dose of 10 × 106, Human fetal MSCs | Intrauterine implantation at 31 weeks of gestation. Thereafter, i.v infusion at 13 month age | Patient was followed for her normal growth trajectory with no alloreactivity from received MSCs |
Infantile Hypophosphatasia | ||||
Whyte et al., 2003 [75] | 8 mo old girl | 2.1 × 106 followed by SCB of 2.92 × 107 mononuclear cells per Kg recipient weight, Haplo-identical marrow stromal cells | Bone marrow transplantation | Striking improvements were seen in skeletal mineralization soon after SCB |
Cahill et al., 2007 [72] | 8 mo old girl | Four bone fragments (2 mm × 10 mm) + MSCs | Two fragments intraperitonealy and two subcutaneously | Bone mineral contents were increased upto 46 % revealed by x-ray absorptiometry. No change in serum alkaline phosphatase levels was observed |
Osteoporosis | ||||
Stenderup et al., 2001 [76] | 13 | 1 × 105 cells per cm2, MSCs from Bone marrow aspirate | - | Bone remodeling and turnover occurred at faster rate in osteoporotic patients. However, it was dependent on the continuous availability of osteoprogenitor cells, growth factors and hormones. |
Osteoarthritis | ||||
Wakitani et al., 2002 [91] | 12 | 1.3 × 107, Autologous MSCs | Surgical implantation | No significant improvement was seen on clinical evaluation, Histological examination revealed hyaline like cartilage |
Centeno et al., 2008 [93] | 1 | 22.4 × 106, MSCs in PBS + PL + dexamethasone | Percutaneous injection | MRI showed improvement in volume of meniscus and cartilage |
Pak, 2011 [92] | 2 | 8.3 cm3, mixture of Autologous ADSCs, PRP, dexamethasone, hyaluronic acid | Intra-articular injection | At 12 week, significant improvement in pain (more than 90 %) and flexion of knee was experienced by patients. MRI revealed improved cartilage thickness |
Davatchi et al., 2011 [94] | 4 | 8-9 × 106, Autologous MSCs | Intra-articular injection | Mild improvement in subjective and objective symptoms was observed. |
Orozco et al., 2013 [95] | 12 | 40 × 106, Autologous MSCs | Intra-articular injection | Algofunctional indices strongly indicated clinical efficacy of injected MSCs. T2 mapping demonstrated significantly improved cartilage quality in 11 out of 12 patients. |
Jo et al., 2014 [96] | 18 | 1.0 × 108 Adipose tissue derived MSCs | Intra-articular Injection | 6 months follow up showed reduction in WOMAC score, MRI findings revealed reduction in the size of cartilage defect |
Vega et al., 2015 [97] | 15 | 40 × 106 allogenic MSCs | Intra-articular Injection | Significant improvements in algofunctional indices versus controls and improvements in the quality of cartilage as assessed by T2 measurements |