Mesenchymal Stem Cell Based Therapy for the Treatment of Osteogenesis Imperfecta
Phase: PHASE1
Conditions: Osteogenesis Imperfecta
Sponsor: Hospital de Cruces

 
Study design 
The Mesenchymal Stem Cell Therapy for the Treatment of Osteogenesis Imperfecta 
(TERCELOI) study was registered with clinicaltrials.gov (NCT02172885) and 
eudract.ema.europa.eu (2012-002553-38). TERCELOI is an independent multi-center 
phase I clinical trial to evaluate the feasibility, safety and potential efficacy of infused 
sibling HLA-matched MSCs in non-immunosuppressed children with OI. Enrolled 
patients were the following: P01, male, 6 years 1 month of age and P02, female, 8 years 
and 1 month of age.   
P01 was born to a healthy and non-consanguineous Spanish couple. Skeletal dysplasia 
was suspected at 24 weeks of gestation. Cesarean delivery was at 34 weeks. At birth 
weight: 1,770 g (p9, -1.4 SD), length: 39 cm (p<1, -3.38 SD), OCF: 30 cm (p3, -1.96 
SD).  X-ray survey showed multiple fractures involving humeri, femur, tibia, and several 
ribs. A genetic study confirmed the clinical diagnosis of OI. A de novo heterozygous 
missense mutation was identified in exon 16 of COL1A1 gene: c.1031G>A 
(p.Gly344Asp). The patient showed blue sclera and developed dentinogenesis 
imperfecta. He had normal neurodevelopment, sitting unsupported at the age of 9 
months. He could never achieve unaided standing up or walking due to compression 
fractures of the spine and limb deformity. The first orthopedic surgical intervention was 
performed at the age of 4.5 years and consisted of correction of bilateral tibia angulation. 
Compassionate intravenous treatment with biphosphonates was initiated at the age of 
57days. He was treated with pamidronate until the age of 5 years and 4 months when 
zoledronate was prescribed instead. Spontaneous fractures or with minimal trauma and 
chronic bone pain have been common manifestations due to the extreme bone fragility. 
P02 was the first child born to a healthy and non-consanguineous couple. Skeletal 
dysplasia was suspected at 34 weeks of gestation. Cesarean breech delivery was at 38 
weeks of gestation. Weight:  2,820g (p 33; -0.44 SD). OFC: 33 cm (p28; -0.4 SD). OI 
was suspected at birth. She had blue sclera, micrognatia, short lower limbs and fracture 

of one clavicle.  X-ray skeletal assessment showed low bone density and prenatal 
fracture of the contralateral clavicle, 8th rib and unilateral cubitus. Genetic studies 
identified a de novo heterozygous variant in the COL1A2 gene: c.2133+6T>A resulting 
in the skipping of exon 35. At the age of two months, the patient revealed severe 
generalized osteopenia, and angulation of both femur and tibia with several areas of 
sclerosis. Compassionate treatment with pamidronate was initiated at the age of 15 
month until the age of 7 years and 10 months when zoledronate was prescribed instead. 
She had normal social and language development. She could walk at the age of three 
years. Recurrent fractures of long bones of the upper and lower limbs leading to bone 
deformities required several surgical interventions. Mobility was largely wheelchair 
dependent.