TEM CELLS ARE UNDIFFERENTIated cells that through replication have the capability of both self-renewal and differentiation into mature specialized cells. In broad terms, there are 2 types of stem cells, embryonic stem cells and adult stem cells. Human embryonic stem cells are isolated from a 50-to 150-cell, 4-to 5-dayold postfertilization blastocyst. Embryonic stem cells generate every specialized cell in the human body and, while capable of indefinite ex vivo proliferation, exist only transiently in vivo (during embryogenesis). Adult stem cells are located in tissues throughout the body and function as a reservoir to replace damaged or aging cells. Under physiologic conditions, adult stem cells are traditionally thought to be restricted in their differentiation to cell lineages of the organ system in which they are located. Embryonic stem cells have great promise and versatility but, compared with adult stem cells, are currently difficult to control due to their tendency to form tumors containing all types of tissue, ie, teratomas. Embryonic stem cell biology has been associated with ethical controversy, and feeder cellfree and xenogeneic-free culture methods approved by the US Food and Drug Administration are still being per-Author Affiliations are listed at the end of this article.

clinicaltrials.gov Identifier: NCT01408901.

Functional impairment, functional decline, and mobility loss are major public health problems in people with lower extremity peripheral artery disease (PAD). Few medical therapies significantly improve walking performance in PAD. We describe methods for the PROgenitor cell release Plus Exercise to improve functionaL performance in PAD (PROPEL) Study, a randomized controlled clinical trial designed to determine whether granulocyte-macrophage colony stimulating factor (GM-CSF) combined with supervised treadmill walking exercise improves six-minute walk distance more than GM-CSF alone, more than supervised treadmill exercise alone, and more than placebo plus attention control in participants with PAD, respectively. PROPEL Study participants are randomized to one of four arms in a 2 by 2 factorial design. The four study arms are GM-CSF plus supervised treadmill exercise, GM-CSF plus attention control, placebo plus supervised exercise therapy, or placebo plus attention control. The primary outcome is change in six-minute walk distance at 12-week follow-up. Secondary outcomes include change in brachial artery flow-mediated dilation (FMD), change in maximal treadmill walking time, and change in circulating CD34+ cells at 12-week follow-up. Outcomes are also measured at six-week and six-month follow-up. Results of the PROPEL Study will have important implications for understanding mechanisms of improving walking performance and preventing mobility loss in the large and growing number of men and women with PAD.

Objective To examine the association between use of statin and non-statin cholesterol-lowering medications and risk of nontraumatic major lower-extremity amputations (LEA) and treatment failure (LEA or death). Design of Study A retrospective cohort of patients with Type I and Type 2 diabetes mellitus (diabetes) was followed for five years between 2004 and 2008. The follow-up exposure duration was divided into 90-day periods. Use of cholesterol-lowering agents, diabetic medications, hemoglobin A1c, body mass index, and systolic and diastolic blood pressures were observed in each period. Demographic factors were observed at baseline. Major risk factors of LEA including peripheral neuropathy, PAD, and foot ulcers were observed at baseline and were updated for each period. LEA and deaths were assessed in each period and their hazard ratios were estimated. Setting US Department of Veterans Affairs Healthcare system (VA) Subjects Cholesterol drug-naïve patients with Type I or II diabetes who were treated in the VA in 2003 and were <65 years old at the end of follow-up. Results Of 83,593 patients in the study cohort, 217 (0.3%) patients experienced a major LEA and 11,716 (14.0%) patients experienced an LEA or death (treatment failure) after a mean follow-up of 4.6 years. Compared to patients who did not use cholesterol-lowering agents, statin users were 35% - 43% less likely to experience an LEA (HR = 0.65; 95% CI, 0.42–0.99) and a treatment failure (HR = 0.57; 95% CI, 0.54–0.60). Users of other cholesterol-lowering medications were not significantly different in LEA risk (HR = 0.95; 95% CI, 0.35–2.60) but had a 41% lower risk of treatment failure (HR = 0.59; 95% CI, 0.51–0.68). Conclusions This is the first study to report a significant association between statin use and diminished amputation risk among patients with diabetes. In this non-randomized cohort, beneficial effects of statin therapy were similar to that seen in large-scale clinical trial experience. For LEA risk, those given non-statins did not have a statistically significant benefit and its effect on LEA risk was much smaller compared to statins.. Unanswered questions to be explored in future studies include a comparison of statins of moderate versus high potency in those with high risk of coronary heart disease and an exploration of whether the effects seen in this study are simply effects of cholesterol-lowering or possibly pleiotropic effects.