In 2002, encouraged by the data from preclinical and clinical studies, Karolinska Institutet performed the first prenatal transplantation of human fetal liver MSC with a successful outcome in an immunocompetent fetus suffering from OI type III.
Prenatal transplantation of fetal MSC into the umbilical vein under ultrasound guidance was performed in gestational week 31. The transplantation showed promising clinical results with long-term donor cell engraftment and site-specific differentiation of MSC in the bone that were shown immunologically not to belong to the transplant recipient. Until eight years of age, the patient had only suffered with one fracture and one compression fracture per year.
Remarkably she continued to grow and follow her own height and weight curve at -5 standard deviations (SD), until from age six to eight years when it deteriorated to -6.5 SD. As a result, and due to an increased fracture rate, the patient was re-transplanted with the same-donor MSC intravenously. Over the following two years, she did not suffer any more fractures and her linear growth and mobility improved.
Karolinska Institutet has followed this patient for more than 14 years and she is now on a yearly transplantation program for four years with the same-donor cells in an attempt to improve her height (during years 2013-2016). After each infusion, a clinical effect was noted (reduced frequency of fractures, increased growth and better quality of life according to her parents). A child with an identical mutation that did not receive pre- or postnatal fetal MSC transplantation exhibited a very severe phenotype of OI and died as a result of the disease at five months of age. This is the first suggestion that prenatal fetal MSC transplantation can improve severe OI in humans.