Stem cell transplantation before birth – a realistic option for treatment of osteogenesis imperfecta?

Abstract

Osteogenesis imperfecta (OI) is characterized by severe bone deformities, growth retardation and bones that break easily, often from little or no apparent cause. OI is a genetic disorder primarily with defective type I collagen with a wide spectrum of clinical expression. In the more severe cases, it can be diagnosed before birth. Transplantation of mesenchymal stem cells (MSC) has the potential to improve the bone structure and stability, growth and fracture healing. Prenatal and postnatal cell transplantation has been investigated in preclinical and clinical studies of OI and suggests that this procedure is safe and has positive effects. Cell transplantation resulted in improved linear growth, mobility and reduced fracture incidence. However, the effect is transient and for this reason re-transplantation may be needed. So far there is limited experience in this area, and proper studies are required to accurately determine if MSC transplantation is of clinical benefit in the treatment of OI. In this review, we summarize what is currently known in this field.

Whole exome sequencing as a diagnostic adjunct to clinical testing in fetuses with structural abnormalities

“…In the future, with the turnaround time getting faster and the cost reducing, couples with fetuses with congenital malformation might be provided with WES in order to make a definitive prenatal diagnosis as early on in pregnancy as possible. This is important for informing parental choice and, where appropriate, guiding delivery plans, treatment on delivery or even in‐utero therapy. Only a minority of the cohort that underwent WES was assessed as trios; this limits the clinical utility of information and detection rate, especially if the genetic sources of variation are deficient.…”

Rapid prenatal diagnosis using targeted exome sequencing: a cohort study to assess feasibility and potential impact on prenatal counseling and pregnancy management

“…Furthermore, definitive molecular diagnosis will be a prerequisite for novel in utero treatment trials such as the Boost Brittle Bones Before Birth study (BOOSTB4), 11 which will offer in utero mesochymal stem cell therapy for osteogenesis imperfecta (OI) types III and IV. 12 A high-throughput multigene sequencing approach is the only way to achieve rapid diagnoses in this time-limited situation. 13 Here, we explored the use of targeted exome sequencing for the rapid genetic diagnosis of fetuses with a suspected skeletal dysplasia as an exemplar of how exome sequencing can be used as an aid to prenatal diagnosis and pregnancy management.…”

Pharmacological and biological therapeutic strategies for osteogenesis imperfecta

“…Bone marrow transplantation was attempted in both animal models and OI patients, with the intention of introducing bone‐forming cells that produce normal type I collagen. Despite low levels of mesenchymal stem cell engraftment, most results showed an increase in BMD, accelerated growth rate, and decreased fracture risk following transplantation, suggesting that the introduction of even a low amount of normal type I collagen may be beneficial to improve the impaired bone quantity and quality in OI [Horwitz et al, ; Otsuru et al, ; Götherström et al, ; Westgren and Gotherstrom, ]. However, this therapeutic approach is currently still considered experimental and controversial with respect to the risks and benefits in patients with OI.…”