Publications

OBJECTIVE

Transdifferentiation of fibroblasts to endothelial cells (ECs) may provide a novel therapeutic avenue for diseases, including ischemia and fibrosis. Here, we demonstrate that human fibroblasts can be transdifferentiated into functional ECs by using only 2 factors, Oct4 and Klf4, under inductive signaling conditions.

APPROACH AND RESULTS

To determine whether human fibroblasts could be converted into ECs by transient expression of pluripotency factors, human neonatal fibroblasts were transduced with lentiviruses encoding Oct4 and Klf4 in the presence of soluble factors that promote the induction of an endothelial program. After 28 days, clusters of induced endothelial (iEnd) cells seemed and were isolated for further propagation and subsequent characterization. The iEnd cells resembled primary human ECs in their transcriptional signature by expressing endothelial phenotypic markers, such as CD31, vascular endothelial-cadherin, and von Willebrand Factor. Furthermore, the iEnd cells could incorporate acetylated low-density lipoprotein and form vascular structures in vitro and in vivo. When injected into the ischemic limb of mice, the iEnd cells engrafted, increased capillary density, and enhanced tissue perfusion. During the transdifferentiation process, the endogenous pluripotency network was not activated, suggesting that this process bypassed a pluripotent intermediate step.

CONCLUSIONS

Pluripotent factor-induced transdifferentiation can be successfully applied for generating functional autologous ECs for therapeutic applications.

OBJECTIVE

The objective of the study was to assess the adherence to hormonal contraception (pill, patch, ring, or injectable) among women veterans and examine the relationships between race/ethnicity and the months of contraceptive supply dispensed with contraceptive adherence.

STUDY DESIGN

We conducted a retrospective analysis of the Department of Veterans Affairs (VA) national databases to examine the adherence to hormonal contraception over 12 months among women aged 18-45 years who had hormonal contraceptive coverage during the first week of fiscal year 2008. We examined several adherence indicators including gaps between refills and months of contraceptive coverage. Descriptive statistics and multivariable models were used to examine the associations between race/ethnicity and contraceptive supply dispensed with adherence.

RESULTS

Our cohort included 6946 women: 47% were white, 6% were Hispanic, 22% were black, and 25% were other race or had missing race information. Most women (83%) received a 3 month supply of contraception at each fill. More than 64% of women had at least 1 gap in coverage of 7 days or longer. Only 22% of women received a full 12 months of contraception without any gaps (perfect adherence). Compared with whites, Hispanics were significantly more likely to experience gaps (64% vs 70%; P = .02), and Hispanics and blacks received fewer months of contraceptive coverage (9.3 vs 8.9 and 9.0, P < .001). Compared with women receiving 3 month supplies, those receiving 1 month supplies had a higher likelihood of a gap (63% vs 72%, P < .001), fewer months of coverage (9.3 vs 6.9, P < .001), and a lower likelihood of perfect adherence (22% vs 11%, P < .001).

CONCLUSION

Adherence to hormonal contraception among women veterans is poor. Efforts to improve contraceptive adherence and lower risk of unintended pregnancy are needed; dispensing more months of supply for hormonal contraception may be a promising strategy.