Allogeneic Mesenchymal Stem Cells as a Treatment for Aging Frailty

As life expectancy is projected to increase in the ensuing decades, individuals of older age continue to exceed the previous generation’s lifespan. Advancing age is associated with a reduction in physical and mental functional capacity, and chronic inflammation is a major factor contributing to this decline. A heightened inflammatory state can lead to exhaustion, weakness, weight loss, slow gate speed, and an overall decrease in activity level. These phenotypes define the onset of the disease process known as frailty. Frailty is a growing epidemic, which severely undermines a person’s ability to deal with outside stressors, and increases their rate of hospitalization, institutionalization, and mortality. Current interventions focus on preventative care by improving exercise capacity, strength, nutritional supplementation, diet, and mobility. However, a biological cure has heretofore remained elusive. Here, we introduce the novel therapeutic principle that mesenchymal stem cell (MSC) therapy may represent a safe, practical, and efficacious both the treatment and prevention of frailty in individuals of advancing age. To date, a phase I safety trial reveals an excellent safety profile and suggests that mesenchymal stem cells can ameliorate signs and symptoms of frailty. These early studies lay the groundwork for future large-scale clinical trials of this exciting and novel therapeutic concept that has the potential to expand health span in the aging population

Allogeneic Mesenchymal Stem Cells as a Treatment for Aging Frailty

As life expectancy is projected to increase in the ensuing decades, individuals of older age continue to exceed the previous generation’s lifespan. Advancing age is associated with a reduction in physical and mental functional capacity, and chronic inflammation is a major factor contributing to this decline. A heightened inflammatory state can lead to exhaustion, weakness, weight loss, slow gate speed, and an overall decrease in activity level. These phenotypes define the onset of the disease process known as frailty. Frailty is a growing epidemic, which severely undermines a person’s ability to deal with outside stressors, and increases their rate of hospitalization, institutionalization, and mortality. Current interventions focus on preventative care by improving exercise capacity, strength, nutritional supplementation, diet, and mobility. However, a biological cure has heretofore remained elusive. Here, we introduce the novel therapeutic principle that mesenchymal stem cell (MSC) therapy may represent a safe, practical, and efficacious both the treatment and prevention of frailty in individuals of advancing age. To date, a phase I safety trial reveals an excellent safety profile and suggests that mesenchymal stem cells can ameliorate signs and symptoms of frailty. These early studies lay the groundwork for future large-scale clinical trials of this exciting and novel therapeutic concept that has the potential to expand health span in the aging population

Off pump coronary artery bypass in patients with an ejection fraction of <20%. What is our strategy?

Patients with left ventricular dysfunction and low ejection fraction (EF) are at high risk of complication and mortality after coronary artery bypass grafting (CABG). The potential success of off‐pump CABG in this high‐risk population has yet to be illustrated. Herein, we present our experience in regards to surgical planning and strategy on how to perform off‐pump CABG in patients with very low EF

Insights Into Signaling in Cell-Based Therapy for Heart Disease

Over the past several decades, stem cell therapy for heart disease has been translated from the bench to the bedside and in clinical trials improves cardiac structure and function in both ischemic and nonischemic cardiac disease. Although the regenerative effects of stem cells in cardiac disease are mediated by both paracrine and cell-to-cell contact mechanisms, many of the downstream signaling pathways remain to be fully elucidated. This review outlines what is currently known about the main signaling pathways involved in mesenchymal stem cell and cardiac stem cell survival, proliferation, and migration and mechanisms of action to repair the damaged heart. </jats:p

Cardiac surgery for Chagas disease

Although Chagas disease is a rare entity in North America, it is associated with significant cardiac morbidity. It is estimated that 20‐30% of those who are infected will eventually develop cardiovascular disease secondary to Chagas disease. We review the literature and share our experience on the surgical management of this challenging patient population

Surgical management of leukoderma after burn: A review

Burns are a common and sometimes devastating injury causing a significant amount of pain, disability, and occasionally death. Burns can have serious aesthetic and functional consequences such as pigmentary changes and formation of scar tissue. Hypopigmentation or depigmentation is often a result of partial- or full-thickness burns, which is referred to as leukoderma after burn. Thus, this study is aimed at systematically reviewing the surgical options for treating leukoderma after burn in order to gain insight into the advantages, disadvantages, and future implications of each surgical technique. The surgical procedures reviewed include dermabrasion with thin split thickness grafting, epidermal cell suspension spray, suction blister epidermal minigrafting, minigrafting, cultured epithelium, noncultured keratinocyte suspension, and chip skin grafting

Abstract 35: Transendocardial Mesenchymal Stem Cell Injection Demonstrates Reverse Remodeling Effects of Global LV Volumes and Enhanced Lateral Papillary Muscle Shortening

Rationale: Secondary mitral regurgitation (MR) carries a poor prognosis despite improvements in surgical and transcatheter interventions. Mesenchymal stem cell (MSC) therapy for heart disease reduces infarct size and left ventricle (LV) dilatation, reverses remodeling, and improves regional contractility and functional capacity. However, it is unknown if the benefits of MSC therapy on LV structure and function apply to lateral papillary muscle shortening, an important predictor of secondary MR severity. Hypothesis: Test the hypothesis that administration of MSCs promotes interpapillary muscle distance (IPMD) shortening. Methods/Results: This retrospective analysis draws on results from autologous or allogeneic MSC injection therapies in a Göttingen swine model of chronic ischemic cardiomyopathy (ICM). MRI was used to measure end-diastolic volume (EDV), end-systolic volume (ESV), diastolic/systolic IPMD, and IPMD shortening. NOGA mapping and angiographic tracings of left ventriculography allowed for assessment of the effect of injection localized to papillary muscles (defined as injection within cardiac segments 4, 6, 10 and 12 in the 16-segment model). Three months after stem cell injection, EDV increased in both placebo- (12.2±3.6 mL; p=0.002) and MSC- (10.2±2.6 mL; p=0.03) treated swine. ESV increased only in placebo- (7.1±2.2 mL; p=0.003) but not MSC- treated swine. Systolic IPMD was maintained with MSC therapy (1.20±0.74 mm; p=0.33) but increased in placebo (1.83±0.60 mm; p=0.01). Systolic IPMD was preserved whether MSC injection was localized to papillary muscle (0.53±0.49 mm; p=0.44) or not (0.22±0.40 mm; p=0.24). Notably, IPMD shortening was significantly greater in MSC- (8.1±5.6%; p=0.02) but not placebo-injected (4.7±5.0%; p=0.69) swine. There were no between group differences in IPMD shortening (p=0.08). Conclusion: This study is the first to show that transendocardial MSC injections significantly enhanced IPMD shortening and lateral interpapillary muscle contraction in a model of chronic ICM. This effect was independent of injection site