A team of scientists has described potential approaches for new treatments to address the root cause of weak and brittle bones in a study (“Engraftment of skeletal progenitor cells by bone directed transplantation improves osteogenesis imperfecta murine bone phenotype”) published in the journal Stem Cells.

The research resulted from a concerted effort involving Brya Matthews, PhD, a researcher at the University of Auckland, New Zealand; and lead investigator Ivo Kalajzic, MD, PhD, the study’s senior author, and his team in the Center for Regenerative Medicine and Skeletal Development in the department of reconstructive sciences at the University of Connecticut School of Dental Medicine.

The researchers noted that Osteogenesis imperfecta (OI) is a genetic disorder most commonly caused by mutations associated with type I collagen, resulting in a defective collagen bone matrix. Current treatments for OI focus on pharmaceutical strategies to increase the amount of defective bone matrix, but do not address the underlying collagen defect.

“Introducing healthy donor stem cells that differentiate into osteoblasts producing normal collagen in OI patients has the potential to increase bone mass and correct the mutant collagen matrix. In this study, donor bone marrow stromal cells (BMSCs, also known as bone marrow mesenchymal stem cells) expressing both αSMACreERT2/Ai9 progenitor reporter and osteoblast reporter Col2.3GFP were locally transplanted into the femur of OI murine (OIM) mice. One month post‐transplantation, 18% of the endosteal surface was lined by donor Col2.3GFP expressing osteoblasts indicating robust engraftment. Long‐term engraftment in the marrow was observed three and six months post‐transplantation,” the investigators wrote.

“The presence of Col1a2‐expressing donor cell derived cortical bone matrix was detected in transplanted OIM femurs. Local transplantation of BMSCs increased cortical thickness (+12%), the polar moment of inertia (+14%), bone strength (+30%), and stiffness (+30%) three months post‐transplantation,” the scientists added. “Engrafted cells expressed progenitor markers CD51 and Sca‐1 up to three months post‐transplantation. Most importantly, three months post‐transplantation donor cells maintained the ability to differentiate into Col2.3GFP+ osteoblasts in vitro, and in vivo following secondary transplantation into OIM animals. Locally transplanted BMSCs can improve cortical structure and strength, and persist as continued source of osteoblast progenitors in the OIM mouse for at least six months.”

Added Kalajzic: “This is a basic research study with potential for future translation into practice.”

The researchers transplanted healthy donor bone marrow cells directly into the femur of mice with OI. One month post-transplantation, the researchers found that 18% of the surface that was injected with the donor cells expressed osteoblasts that indicated engraftment, or growth. Long-term engraftment was then observed three and six months post-transplantation. The researchers found that healthy donor cells that replace mutant collagen have the ability to help improve bone strength and structure.

The study proved that healthy donor stem cells that produce normal collagen in OI patients have the potential to increase bone mass and correct the mutant collagen matrix, explained Kalajzic, adding that the findings unlock the potential for new therapies to help correct the adverse effects of OI.

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