Systemically administered mesenchymal stromal cells transduced with insulin-like growth factor-I localize to a fracture site and potentiate healing.

OBJECTIVE: To determine to the ability of systemically administered pluripotential mesenchymal stromal cells to localize to a fracture site and whether transduction with a therapeutic gene, insulin-like growth factor-I (D1-IGF-I), could potentiate healing. DESIGN: Murine model, basic science study. SETTING: Laboratory. SPECIMENS: Closed, transverse, mid-shaft femur fractures were produced in 108 Balb/c mice after intramedullary stabilization. INTERVENTIONS: A cloned, pluripotential, mesenchymal cell line, termed D1, was stably transfected with either the gene beta-galactosidase (D1-BAG) as a histologic marker or with the gene IGF-I (D1-IGF-I) growth factor. Mice received systemic injections of either D1-BAG cells for in vivo localization or D1-IGF-I for therapeutic intervention. A third group received lactated Ringer's solution and served as control. MAIN OUTCOME MEASUREMENTS: Sections obtained from the fracture site and contralateral femurs were examined histologically and by deoxyribonucleic acid-polymerase chain reaction (DNA-PCR) to detect the presence of transplanted cells at 2, 4, and 6 weeks after fracture. Matrix mineralization and callus maturation were evaluated by histology. RESULTS: At all time points, using histologic staining with X-gal and deoxyribonucleic acid-polymerase chain reaction for marker genes, there was a statistically greater number of transplanted cells ( p< 0.001) and significantly higher DNA-PCR for marker genes ( p< 0.001) in the fractured femurs than in the nonfractured femurs. Mice receiving D1-IGF-I cells demonstrated a greater percent of mineralized callus than controls at two weeks (p < 0.05). At 4 and 6 weeks, treated mice demonstrated on average greater mineralized matrix and accelerated progression to an osseous callus as compared with the control group. CONCLUSIONS: Cell-based gene therapy has the potential to deliver higher therapeutic levels of growth factors specifically at the site of cell localization while minimizing wider systemic side effects. This study demonstrates that systemically injected IGF-I transduced, mesenchymal cells are able to return to and repopulate the bone marrow. More importantly, these cells localize preferentially to a fracture site and accelerated fracture healing.

Postpartum depression, urge urinary incontinence, and overactive bladder syndrome: is there an association?

The purpose of this prospective, cross-sectional study was to determine if there was an association between postpartum depression and symptoms of overactive bladder in postpartum women. At their 6 week postpartum visit, participants completed questionnaires regarding lifestyle, personal health, urinary incontinence, and depression symptoms, including the Urge-Urinary Distress Inventory (URGE-UDI), the Urge-Incontinence Impact Questionnaire (URGE-IIQ), and the Edinburgh Postnatal Depression Scale (EPDS). Past medical history, including obstetric variables, family history, and medications were extracted from the medical record. One hundred patients completed the questionnaires at the University of Michigan Hospital and 46 patients at the University of Virginia Hospital (mean age 29.2+/-6.1 years; 18-47 years) at their postpartum visit (mean time 45.2+/-9.4 days postpartum; 11-79 days). Sixteen percent of the women had depression (EPDS score of >12) or were borderline (EPDS score of 9-12) for postpartum depression. There was no difference in age and race in women with and without depression. Type of delivery, vaginal vs cesarean section did not significantly impact their URGE-UDI or URGE-IIQ score. There was a significant correlation between the URGE-IIQ score and depression (0.24, p=0.003), but not the URGE-UDI score. In this cross-sectional study, we found an association between postpartum depression and symptoms of urge incontinence. Because birth is a predictable event, further studies evaluating the causal relationships and physiologic changes linking depression and incontinence can be studied using this model.