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Stem Cells Signal Mouse's Own Cells To Mend The Fracture

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Treatment with bone marrow-derived stem cells could prove to be an effective strategy for slow healing bone fractures in diabetics, a pre-clinical study suggested.

When nondiabetic human bone marrow-derived mesenchymal stem cells (hMSCs) were administered directly to femur fractures in a murine model of diabetes, the bones healed more efficiently than nontreated bone, reported Cynthia Coleman, PhD, of the National University of Ireland in Galway, and colleagues.

he stem-cell treated bones were also significantly stronger than nontreated bone, they stated in a report at the 2015 European Congress of Endocrinology (ECE) meeting.

Both the metabolic and endocrine impact of diabetes can adversely affect bone quality and may increase fracture risk. Lower bone mass and increased fracture risk have long been recognized as a complication of type 1 diabetes, and fracture is also increasingly recognized as a concern for patients with type 2 diabetes, despite their often higher, obesity-related bone density.

Fractures in patients with both type 1 and type 2 diabetes are also slower to heal, and diabetic patients have an increased risk for suboptimal healing.
In an ECE abstract, Coleman and colleagues wrote that, "given the known deficiencies in diabetic progenitor cell number and differentiation capacity, it is reasonable to hypothesize the etiology of diabetic fracture malunion is dysregulated progenitor function."

To test this hypothesis, they performed a 56-day, dose escalation study in which they administered hMSCs locally to femoral fractures in the diabetic mouse model.

The mice were evaluated weekly, which included monitoring of their weight, blood glucose levels, and terminal levels of circulating HbA1c. Both animals treated with the hMSCs and control animals treated with saline had similar body weight, blood glucose levels, and HbA1c levels over the course of the study.

Micro CT analysis revealed an increase in bone volume, along with a statistically significant decrease in the ratio of bone surface area to bone volume in animals treated with hMSCs, compared with the saline-treated animals.

Additional analysis, using the four-point bending strategy, showed a statistically significant increase in ultimate stress and e-modulus of the repairing bone, the researchers noted.

"Although the local administration of hMSCs did not alter the organismal diabetic condition, treatment of the diabetic fracture with hMSCs resulted in enhanced mechanical integrity of de novo reparative bone," they wrote.

The researchers were also able to determine that the stem cells did not permanently integrate into the mouse host tissue. Instead, the cells produced signals that prompted the mouse's own cells to heal the fracture.

"This basic science study allows us to better understand the role of stem cells in fracture repair and potential use in treating diabetic patients," Coleman noted in a press statement. "Stem cells represent an exciting potential for improving the treatment and lessening the pain and discomfort of diabetic people who break bones."

Source : http://goo.gl/zaZF27

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