Safety of intrathecal injection of Wharton's jelly-derived mesenchymal stem cells in amyotrophic lateral sclerosis therapy.

Animal experiments have confirmed that mesenchymal stem cells can inhibit motor neuron apoptosis and inflammatory factor expression and increase neurotrophic factor expression. Therefore, mesenchymal stem cells have been shown to exhibit prospects in the treatment of amyotrophic lateral sclerosis. However, the safety of their clinical application needs to be validated. To investigate the safety of intrathecal injection of Wharton's jelly-derived mesenchymal stem cells in amyotrophic lateral sclerosis therapy, 43 patients (16 females and 27 males, mean age of 57.3 years) received an average dose of 0.42 × 106 cells/kg through intrathecal administration at the cervical, thoracic or lumbar region depending on the clinical symptoms. There was a 2 month interval between two injections. The adverse events occurring during a 6-month treatment period were evaluated. No adverse events occurred. Headache occurred in one case only after first injection of stem cells. This suggests that intrathecal injection of Wharton's Jelly-derived mesenchymal stem cells is well tolerated in patients with amyotrophic lateral sclerosis. This study was approved by the Bioethical Committee of School of Medicine, University of Warmia and Mazury in Olsztyn, Poland (approval No. 36/2014 and approval No. 8/2016). This study was registered with the ClinicalTrials.gov (identifier: NCT02881476) on August 29, 2016.

Cartilage Repair in the Knee Using Umbilical Cord Wharton's Jelly-Derived Mesenchymal Stem Cells Embedded Onto Collagen Scaffolding and Implanted Under Dry Arthroscopy.

Cell-based cartilage repair procedures are becoming more widely available and have shown promising potential to treat a wide range of cartilage lesion types and sizes, particularly in the knee joint. More recently, techniques have evolved from 2-step techniques that use autologous chondrocyte expansion to 1-step techniques that make use of mesenchymal stem cells (MSCs) embedded onto biocompatible scaffolding. Our 1-step technique has been further developed to provide cell-based cartilage repair using MSCs that have the potential to be used in an off-the-shelf manner, without the need for autologous tissue harvest. Precursor MSCs can be isolated in abundance from the Wharton's jelly of umbilical cord tissue. These cells have been shown to have the desired capacity for proliferation, differentiation, and release of trophic factors that make them an excellent candidate for use in the clinical setting to provide cell-based restoration of hyaline-like cartilage. Although allogeneic in nature, these cells stimulate little or no host immune response and can be stored for long periods while maintaining viability. We present a technique of cartilage repair in the knee using Wharton's jelly-derived MSCs embedded onto scaffolding and implanted in a minimally invasive fashion using dry arthroscopy.

Immune Abnormalities in Autism Spectrum Disorder-Could They Hold Promise for Causative Treatment?

Autism spectrum disorders (ASD) are characterized by impairments in language and communication development, social behavior, and the occurrence of stereotypic patterns of behavior and interests. Despite substantial speculation about causes of ASD, its exact etiology remains unknown. Recent studies highlight a link between immune dysfunction and behavioral traits. Various immune anomalies, including humoral and cellular immunity along with abnormalities at the molecular level, have been reported. There is evidence of altered immune function both in cerebrospinal fluid and peripheral blood. Several studies hypothesize a role for neuroinflammation in ASD and are supported by brain tissue and cerebrospinal fluid analysis, as well as evidence of microglial activation. It has been shown that immune abnormalities occur in a substantial number of individuals with ASD. Identifying subgroups with immune system dysregulation and linking specific cellular immunophenotypes to different symptoms would be key to defining a group of patients with immune abnormalities as a major etiology underlying behavioral symptoms. These determinations would provide the opportunity to investigate causative treatments for a defined patient group that may specifically benefit from such an approach. This review summarizes recent insights into immune system dysfunction in individuals with ASD and discusses the potential implications for future therapies.

[High plasma folate in patients with phenylketonuria]. / Hiperfolacynemia u chorych na fenyloketonurie.

UNLABELLED: Phenylketonuria is an inborn error of metabolism treated with a closely monitored low phenylalanine diet. Protein substitutes used for treatment are supplemented with vitamins and micronutrients. AIM: The aim of this study was to investigate plasma folic acid concentrations in children with phenylketonuria. MATERIALS AND METHODS: Retrospective analysis of medical records of 73 patients with phenylketonuria and 28 with mild hyperphenylalaninemia (on normal diet) was carried out. Intake of folic acid was calculated on the basis of protein substitute intake. Folate concentrations were analyzed according to their intake, and concentration of homocysteine and phenylalanine. RESULTS: In 76.7% patients with phenylketonuria intake of folic acid exceeded recommended dietary allowance. Serum folic acid concentrations above upper reference level were detected in 75.3% patients with phenylketonuria and only in 25% patients with hyperphenylalaninemia (p<0.0001). Strong positive correlation between daily intake of folic acid (with protein substitute) and concentration plasma folic acid (corr=0.55, p<0.0001) has been observed. CONCLUSIONS: Low phenylalanine diet using protein substitutes currently available in Poland predisposes to high concentration of plasma folic acid. The security of folic acid hipersupplementation in patients with phenylketonuria requires further detailed research.

Stem cell regenerative therapy in alveolar cleft reconstruction.

Achieving a successful and well-functioning reconstruction of craniofacial deformities still remains a challenge. As for now, autologous bone grafting remains the gold standard for alveolar cleft reconstruction. However, its aesthetic and functional results often remain unsatisfactory, which carries a long-term psychosocial and medical sequelae. Therefore, searching for novel therapeutic approaches is strongly indicated. With the recent advances in stem cell research, cell-based tissue engineering strategies move from the bench to the patients' bedside. Successful stem cell engineering employs a carefully selected stem cell source, a biodegradable scaffold with osteoconductive and osteoinductive properties, as well as an addition of growth factors or cytokines to enhance osteogenesis. This review highlights recent advances in mesenchymal stem cell tissue engineering, discusses animal models and case reports of stem cell enhanced bone regeneration, as well as ongoing clinical trials.

[Etiology and own experience in the primary monosymptomatic nocturnal enuresis in children]. / Etiologia i doSwiadczenia wLasne w pierwotnym monosymptomatycznym moczeniu nocnym u dzieci.

UNLABELLED: Primary monosymptomatic nocturnal enuresis (PMNE) is the most frequent (85%) type of enuresis in children. It remains a diagnostic and therapeutic challenge to establish its etiology and implement a proper treatment. AIM: The aim of the study was to establish the causes of PMNE in children on the basis of own investigations and assess factors having influence over PMNE etiology, which would enable the choice of effective therapy. MATERIALS AND METHODS: The study concerned 85 children with PMNE aged from 5 to 15 years. The patients were under the care of Nephrology Outpatient Clinic at Institute of Mather and Child in years 2009-2014. The detailed medical history, physical examination as well as laboratory investigations of blood and urine, and radiological investigations of the urinary tract, were carried out. Statistical analysis was performed using R software. RESULTS: In all patients, we have successfully detected the etiology of children of PMNE. The basic, equally frequent (62.3%), PMNE etiopathogenetic factors turned to be: too small bladder capacity resulting from the detrusor hyperactivity, and night polyuria mainly caused by vasopressin deficiency or abnormal eating and hygienic habits, occurring separately or in conjunction with each other. Too small bladder capacity occurred mainly (37.6%, group C) as the only etiological factor of PMNE, and in 24.7% (group A) in a conjunction with nocturnal polyuria due to decreased excretion of vasopressin. Night polyuria was caused by the deficiency of vasopressin in most cases (37.6%) and occurred mainly (24.7%, group D) in a conjunction with small bladder capacity, and rarely alone (12.9%, group B). In 24.7% (group A) it appeared due to eating and hygienic abnormal habits. We have proved statistically significant differences in mean voiding frequency and volume (p<0.0001) between groups A-B and C-D. Mean morning urine specific gravity (p<0.0001) also differed significantly between group C and B (p<0.0001) as well as C and D (p=0.0004). CONCLUSIONS: PMNE in all patients was attributed to specific causes outside the circle of psychological disorders what reduced patient stigmatization. PMNE etiology is very complex and diverse. It still remains a challenge and requires and individual diagnostic and therapeutic approach. Voiding frequency above 8 daily with voiding volumes usually below 100 ml suggest etiology connected with small bladder capacity, while morning urine specific gravities below 1.021 g/ml can be connected with vasopressin deficiency or excessive fluid intake before the bedtime. The developed diagnostic approach along with borderline values are hints that can aid physicians in establishing PMNE causes.