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Abstract
Nonunion of fractures remains a challenging and frequently encountered
problem in orthopedic surgery. During normal fracture healing undifferentiated mesenchymal progenitor cells, with aid of bone morphogenic protein (BMPs) and regulatory cytokines proliferate, differentiate into chondrocytes and osteoblasts and form bone, thereby repairing the injury. Some fractures however fail to heal leading to morbidity and functional limitations for the patients. The diagnosis of nonunion is based on a combination of clinical symptoms and physical findings, including pain and motion at fracture site with radiographic
evidence of failure of union. Although there is no universally accepted
definition of nonunion, it can be considered the failure of fracture to heal in six to eight months without any further progress toward healing. The
incidence of nonunion varies by fracture site but can be high as 5% to 20%.
The causes of nonunion are multifactorial and may be categorized by
fracture,host, and surgical factors. There may include soft tissue damage,
loss of vascularity,distraction of fracture fragements,soft tissue
interposition,malnutrition, infection, instability,periosteal stripping, and
systemic disease.
The potential of stem cells for therapeutic clinical use arises from their normal role in tissue repair and their presence in essentially every tissue and organ in the body, including bone and hematopoietic marrow. Stem cells are primitive, unspecialized cells with two main characteristics: the ability for self renewal indefinitely and the ability to differentiate into distinct lineages
of mature cells. The developmental potential of stem cells can be described
as totipotent, pleuripotent or multipotent.
There are two major classes of stem cells based on their origin,
embryonic and adult stem cells. Embryonic stem cells are pleuripotent cells isolated from inner cell mass of blastocyst that can be propagated
indefinitely in an undifferentiated state. Adult stem cells are multipotent
cells found in specific tissue compartment in the body with more limited regenerative capability. The two main types of adult stem cells,
hematopoietic and mesenchymal, both have clinical potential.
Because of their abundance in the body, their tolerance for invitro expansion, and their ability to differentiate into many types of tissue, including bone, tendon, cartilage, ligaments, and other tissue of mesenchymal origin, stem cells hold infinite potential for clinical use in orthopedic surgery, especially in the repair and regeneration of bone.
Stem cells have also been genetically engineered to express transgenes of
osteogenic proteins. This would decrease the number of mesenchymal stem
cells needed for implantation and possibly eliminate the need for in vitro
culture and expansion. The secreted protein exerts autocrine and paracrine
effects, leading to the differentiation of the engineered stem cell and to the
recruitment of host stem cells in vivo. Most often these studies have involved BMPs. Human adipose derived stem cells have been transduced with BMP-2 and applied to collagen-ceramic carrier to heal critical size femoral defects in rats resulted in significant bone formation. Placing adipose derived stem cells alone on the carrier did not result in significant bone formation.