Effective Healing of Leprosy Chronic Plantar Ulcers by Application of Human Amniotic Membrane Stem Cell Secretome Gel.

BACKGROUND: Chronic plantar ulcers are common problems for leprosy patients with numb feet due to their prolonged healing time. Chronic plantar ulcers affect the quality of life of patients and can lead to more serious complications, such as disability and deformity, if not handled appropriately. Wound-care products in the market, however, give unsatisfactory results. One factor in the delayed healing of chronic plantar ulcers due to leprosy is the lack of growth factors and cytokines in the wound due to reduced blood supply. We speculated that application of human amniotic membrane stem cell (hAMSC) secretome, which contains growth factors and cytokines, could improve wound healing. AIM: To evaluate the effect of topical application of a hAMSC secretome gel on wound healing of chronic plantar ulcers due to leprosy. MATERIALS AND METHODS: We recruited 11 patients after leprosy treatment with chronic plantar ulcers due to leprosy. hAMSC secretome gel was applied topically to ulcers every 3 days for up to 2 months. Ulcer size and possible side effects or complications from gel application were evaluated weekly. RESULTS: The ulcers of 8 of 11 patients (72.7%) completely healed, the ulcers of 2 patients (18.2%) partially healed, and the ulcers of 1 patient (9.1%) persisted. No ulcers became worse. CONCLUSION: hAMSC secretome was found to be an efficacious and well-tolerated alternative therapy for chronic plantar ulcers due to leprosy.

Lactobacillus plantarum IS-10506 activates intestinal stem cells in a rodent model.

This study investigated the probiotic effect of Lactobacillus plantarum IS-10506 in activating and regenerating leucine-rich repeat-containing G-protein-coupled receptor (Lgr)5- and B lymphoma Moloney murine leukaemia virus insertion region (Bmi)1-expressing intestinal stem cells in rodents following Escherichia coli serotype 055:B5 lipopolysaccharide (LPS) exposure. Male Sprague-Dawley rats (n=64) were randomised into control (KN), LPS (KL), probiotic + LPS (KL-Pr), and sequential probiotic + LPS + probiotic (KPR-7L) groups. Microencapsulated L. plantarum IS-10506 (2.86×1010 cfu/day) was administered via a gastric tube once daily for up to 7 days, and LPS (250 ng/kg body weight) was administered via a gastric tube on the first day of the experiment to all but the KN group. On day 3, 4, 6, and 7, four rats per group were sacrificed, and Lgr5, Bmi1, extracellular signal-regulated kinase (ERK), and ß-catenin expression in the ileum was assessed by immunohistochemistry. LPS treatment reduced Lgr5 (P≤0.05) and Bmi1 (P=0.000) levels in intestinal epithelial cells, whereas probiotic treatment increased levels of Lgr5 (KPR-7L, P=0.008) and Bmi1 (KL-Pr, P=0.008; and KPR-7L, P=0.000). Lgr5 expression was upregulated in the KL-Pr group on day 3, 4, 6, and 7 (P=0.056). Additionally, ERK levels were elevated in Bmi1- and Lgr5-expressing cells in rats treated with probiotics (KL-Pr and KPR-7L), whereas ß-catenin levels were increased in Lgr5-expressing cells from KPR-7L rats and in Bmi1-expressing cells from KL-Pr and KPR-7L rats on day 3 and 4. These results demonstrated that the probiotic L. plantarum IS-10506 activated intestinal stem cells to counter inflammation and might be useful for maintaining intestinal health, especially when used as a prophylactic agent.

The efficacy of topical human amniotic membrane-mesenchymal stem cell-conditioned medium (hAMMSC-CM) and a mixture of topical hAMMSC-CM + vitamin C and hAMMSC-CM + vitamin E on chronic plantar ulcers in leprosy:a randomized control trial.

BACKGROUND: Healing of chronic plantar ulcers in leprosy (CPUL) typically takes a long time due to impaired neurological function, thereby reducing the levels of growth factors and cytokines. Cytokines can be found in metabolite products from amniotic membrane stem cells. Chronic ulcers are frequently characterized by high levels of reactive oxygen species. Vitamin E (α-tocopherol) is widely used in skin lesions, owing to its antioxidant and anti-inflammatory properties. Vitamin C also has antioxidant, anti-inflammatory, and collagen synthesis properties which are useful in wound healing. Herein, we compared the effects of topical human amniotic membrane-mesenchymal stem cell-conditioned medium (hAMMSC-CM) alone and with vitamins C and E on healing of CPUL. METHODS: In this randomized controlled trial, topical agents were applied every 3 days for up to 8 weeks. Ulcer size, side-effects, and possible complications were monitored weekly. RESULTS: Healing percentage increased each week in all groups. Mean difference in ulcer size was highest in the hAMMSC-CM + vitamin E group, implying better progress of wound healing. There were no side-effects or complications. CONCLUSIONS: hAMMSC-CM + vitamin E is best for healing of CPUL.

First isolates of infectious human Borna disease virus from patients with mood disorders.

Borna disease virus (BDV), an unique type of non-segmented negative-stranded enveloped RNA virus, is known as an animal pathogen that causes behavioral diseases in higher vertebrates. Past studies have found antibodies to BDV as well as BDV proteins and genomic transcripts in peripheral blood mononuclear cells (PBMCs) of infected animals and human psychiatric patients. Here, we present the first isolation of infectious BDV from such patients' PBMCs. Isolation attempts were conducted with randomly collected PBMC samples from 33 psychiatric inpatients, by co-cultivation and long-term passaging with a human cell line. BDV isolates were identified by infectivity, analysis of viral antigens, sequencing of one viral gene, and successful infection of animals. Three individual isolates could be recovered. They originated from two bipolar patients with acute depression, and one patient with a chronic obsessive-compulsive disorder. Rescue of human BDV required PBMC samples with strong viral antigen expression, and at least 11 subcultures per sample. Genetic and biological properties point to a close relationship of human and animal strains, but also to the uniqueness of each human isolate. Isolation of BDV from patients with major mood disorders at a time of acute depression strengthens the possibility that BDV infection is one of the environmental factors that contributes to recurrent depressive illnesses in man. These isolates represent the first three defined strains of the infectious human BDV.