Background
Large craniofacial bone defects, which are caused by various conditions, including trauma, infection, tumors, congenital disorders, and progressive deforming diseases, are major health issues. To date, the recommended procedure for skeletal repairs is autologous bone graft, a process by which bone fragments are harvested from one anatomic site and transplanted to another site in the same patient. Unfortunately, this process still remains highly challenging due to several limitations such as donor site pain (the most common complication), increased blood loss, increased operative time, infections and limited supply. Alternative approaches have been explored like stem cell-based therapy, but there are still significant hurdles that restrict further advances in this field such as the lack of a cell surface marker to allow for stem cell isolation and the inability to maintain the self-renewal and differentiation characteristics when taken out of the body. Therefore, there is a need to develop new methods to successfully isolate stem cells for later use in bone regeneration and repair.
Technology Overview
Bone morphogenetic proteins (BMPs) have the ability to induce the formation of bone and cartilage. Rochester researchers have identified BMPR1A, a BMP receptor, essential for maintaining stemness (capacity of self-renewal and differentiation) in skeletal stem cells. Because BMPR1A is a cell surface protein (aka CD292) expressed in the skeletal stem cells, it allows for specific isolation of these cells, which can later generate bone at an ectopic site upon transplantation. A new method has also been developed to maintain the stemness of skeletal stem cells in the laboratory. After a long-term culture, transplantation analysis shows the cultured skeletal stem cells are capable of generating bones in vivo.
Benefits
This protocol allows for the culture of skeletal stem cells for an extended period of time while retaining their ability to generate bone tissue upon implantation into a different anatomical site. BMPR1A also serves as a marker to isolate human and mouse skeletal stem cells
Applications
There is an important use of skeletal stem cell-mediated bone regeneration and repair in clinical therapy for various settings related to large bone defects and fracture healings.