Therapeutic Lymphangiogenesis Is a Promising Strategy for Secondary Lymphedema.

Secondary lymphedema is caused by lymphatic insufficiency (lymphatic drainage failure) following lymph node dissection during the surgical treatment or radiation therapy of breast or pelvic cancer. The clinical problems associated with lymphedema are reduced quality of life in terms of appearance and function, as well as the development of skin ulcers, recurrent pain, and infection. Currently, countermeasures against lymphedema are mainly physical therapy such as lymphatic massage, elastic stockings, and skin care, and there is no effective and fundamental treatment with a highly recommended grade. Therefore, there is a need for the development of a fundamental novel treatment for intractable lymphedema. Therapeutic lymphangiogenesis, which has been attracting attention in recent years, is a treatment concept that reconstructs the fragmented lymphatic network to recover lymphatic vessel function and is revolutionary to be a fundamental cure. This review focuses on the translational research of therapeutic lymphangiogenesis for lymphedema and outlines the current status and prospects in the development of therapeutic applications.

Therapeutic angiogenesis for patients with no-option critical limb ischemia by adipose-derived regenerative cells: TACT-ADRC multicenter trial.

BACKGROUND: Patients with critical limb ischemia (CLI) still have a high rate of lower limb amputation, which is associated with not only a decrease in quality of life but also poor life prognosis. Implantation of adipose-derived regenerative cells (ADRCs) has an angiogenic potential for patients with limb ischemia. OBJECTIVES: We investigated safety, feasibility, and efficacy of therapeutic angiogenesis by cell transplantation (TACT) of ADRCs for those patients in multicenter clinical trial in Japan. METHODS: The TACT-ADRC multicenter trial is a prospective, interventional, open-labeled study. Patients with CLI (Fontaine class III-IV) who have no other option for standard revascularization therapy were enrolled in this study. Thirty-four target ischemic limbs of 29 patients were received freshly isolated autologous ADRCs implantation. RESULTS: The overall survival rate at a post-operative period and at 6 months follow-up was 100% at any time points. As a primary endpoint for efficacy evaluation, 32 limbs out of 34 (94.1%) were free from major amputation for 6 months. Numerical rating scale (from 6 to 1) as QOL score, ulcer size (from 317 mm2 at to 109 mm2), and 6-min walking distance (from 255 to 369 m) improved in 90.6%, 83.3%, and 72.2% patients, respectively. CONCLUSIONS: Implantation of autologous ADRCs could be safe and effective for the achievement of therapeutic angiogenesis in the multicenter settings, as a result in no major adverse event, optimal survival rate, and limb salvage for patients with no-conventional option against critical limb ischemia. TRN: jRCTb040190118; Date: Nov. 24th, 2015.

Gut microbial metabolite short-chain fatty acids and obesity.

Over the past decade, the gut microbiota has emerged as an essential mediator in the pathophysiology of obesity and related metabolic disorders. In this context, the reciprocal interactions of the gut microbiota structure and their metabolite profiles with host metabolism predisposing to a range of pathological conditions (e.g., insulin resistance) related to energy homeostasis have been increasingly discussed in various animal models and human cohorts. Remarkably, as the role of gut microbial metabolites as critical signaling molecules that function through the complementary host receptors has come to be appreciated, tremendous attention has been focused on the proposed diet-gut microbiota-host homeostasis axis, entailing extensive cross-disciplinary efforts in medical, pharmaceutical, and agricultural sciences. This review will discuss the recent advances in understanding the mechanisms whereby the gut microbiota modulates the effects of diet and shapes the host metabolism either towards or away from obesity and related metabolic conditions. In particular, the interactions of short chain fatty acids (SCFAs), a subset of key gut microbial metabolites, with their specific receptors will be reviewed in relation to host energy homeostatic regulation and evaluated for potential as novel therapeutic targets for diet-induced obesity.