Relocating to a new facility: The challenge of a cord blood banking transferral in Brazil.

BACKGROUND: Our cord blood banking facility planned and executed a transferral of its entire operation to a new site in the South of Brazil. Transporting LN2 freezers is a complex process in which extensive planning is essential to minimize the risks of damaging products or storage units. METHODS: To fulfill this objective, we constructed a detailed relocation plan consisting of four phases and risk mitigation measures, collaborated with the representatives of all departments, regulating agencies, and professionals from the transport company, and assembled a validation plan for cryogenic freezers and the viability of cord blood units. RESULTS: The new facility was prepared in accordance with the project plan, local legislation, quality system program requirements, and accreditation agency guidance. A 12-h operation of moving the cryogenic freezers was conducted successfully, with no loss or damage of client samples or equipment. CONCLUSION: Through the development and execution of a transferral plan, the engagement of appropriate partners, and compliance with security measures from health and government agencies, a successful transferral of a cord blood banking facility operation in its entirety can be successfully accomplished.

Manufacturing Parameters for the Creation of Clinical-Grade Human-Induced Pluripotent Stem Cell Lines From Umbilical Cord Mesenchymal Stromal Cells.

Induced pluripotent stem cells (iPSCs) are reprogrammed cells with a remarkable capacity for unlimited expansion and differentiation into various cell types. Companies worldwide are actively engaged in developing clinical-grade iPSC lines to address the needs of regenerative medicine, immunotherapies, and precision medicine. However, ensuring the safety and quality of iPSCs is essential, with adherence to Good Manufacturing Practices (GMP) and ethical considerations being paramount. Perinatal cell and tissue banks, such as umbilical cord (UC) blood and tissue banks, are emerging as ideal sources for generating iPSCs due to their unique characteristics and GMP compliance. These banks provide access to immature cells with limited environmental exposure, known family and medical histories of donors, and readily available resources, thereby reducing the time and cost associated with personalized treatment strategies. This study describes the establishment of the first clinical-grade iPSC lines from umbilical cord mesenchymal stromal cells in Brazil. The process involved rigorous quality control measures, safety assessments, and adherence to regulatory standards, resulting in iPSCs with the necessary characteristics for clinical use, including sterility, genomic integrity, and stability. Importantly, the study contributes to the development of a Current Good Manufacturing Practice-compliant iPSC production pipeline in Brazil, using commercially available, chemically defined, and xeno-free products, along with validation by national outsourced laboratories, thereby facilitating the adoption of this technology within the country. The study emphasizes Brazil's contribution to the progress of translational medicine and the promotion of scientific advancements within the field of regenerative and precision medicine.

A novel method to pack cryopreserved amniotic membrane for wound dressing-the pathway through validation of a new biological product.

Amniotic membrane (AM) has been widely used as a biological dressing for many pathologies and illnesses worldwide, and products derived from this tissue have been commercially available in several countries. In Brazil, regulatory agencies have recently authorized its clinical use as a non-experimental therapy for burns, diabetic and venous stasis ulcers, and intrauterine adhesions. In this study, we present our pathway through validating the first available service in the country of AM cryopreservation, with a protocol for long-term storage in high-efficiency nitrogen cryogenic freezers and a specific way of packing the tissue for optimal clinical handling and efficient storage space utilization while preserving live cells and the tissue's biological properties. Using gauze as support, cryoprotectant dimethyl sulfoxide and product presentation as a multilayer roll exhibited the best cell viability results and maintained the tissue integrity and presence of stem/progenitor cells. Essential proteins involved in tissue regeneration and immune and antimicrobial control were detected from the secretome of cryopreserved tissue similar to fresh tissue. Furthermore, immunogenic markers, such as human leukocyte antigens, were detected at very low levels in the tissue, confirming their low immunogenicity. Finally, we demonstrate that the tissue can be kept under refrigerated conditions for up to 7 d for further use, maintaining sterility and considerable cell viability. Our cryopreservation and storage protocol kept the AM viable for at least 20 months. In conclusion, this study enabled us to determine a novel efficient protocol for long-term AM preservation for future clinical applications.

Reactive Astrocytes Promote ALS-like Degeneration and Intracellular Protein Aggregation in Human Motor Neurons by Disrupting Autophagy through TGF-ß1.

Amyotrophic lateral sclerosis (ALS) is a fatal and rapidly progressing motor neuron disease. Astrocytic factors are known to contribute to motor neuron degeneration and death in ALS. However, the role of astrocyte in promoting motor neuron protein aggregation, a disease hallmark of ALS, remains largely unclear. Here, using culture models of human motor neurons and primary astrocytes of different genotypes (wild-type or SOD1 mutant) and reactive states (non-reactive or reactive), we show that reactive astrocytes, regardless of their genotypes, reduce motor neuron health and lead to moderate neuronal loss. After prolonged co-cultures of up to 2 months, motor neurons show increased axonal and cytoplasmic protein inclusions characteristic of ALS. Reactive astrocytes induce protein aggregation in part by releasing transforming growth factor ß1 (TGF-ß1), which disrupts motor neuron autophagy through the mTOR pathway. These results reveal the important contribution of reactive astrocytes in promoting aspects of ALS pathology independent of genetic influences.

A uterine cavity-myoma communication after uterine artery embolization: two case reports.

OBJECTIVE: To report two cases of uterine cavity-myoma fistula as a medical complication after uterine artery embolization. DESIGN: Case report. SETTING: Women's Medical Center/Viscomi Institute, Sao Paulo, Brazil. PATIENT(S): Two patients presenting with symptomatic myomatous uterus: a 40-year-old woman with increased abdominal volume and hypermenorrhea, and a 42-year-old woman with pelvic pain and infertility. INTERVENTION(S): Uterine artery embolization, hysteroscopic follow-up, and laparoscopic myomectomy. MAIN OUTCOME MEASURE(S): Hysteroscopic follow-up after uterine artery embolization. RESULT(S): The patients underwent uterine artery embolization. In the months that followed, a subsequent surgical hysteroscopic follow-up was performed to eliminate the necrotic material of the degenerated myomas. The two patients presented the same outcome 1 year after the uterine artery embolization had been performed: a communication between the uterine cavity and a degenerated myoma. Laparoscopic correction of the uterine wall defect was performed afterward. CONCLUSION(S): Because embolization is a growing option for the treatment of leiomyoma, it is important that potential complications be reported, especially if the patients want to become pregnant. The natural history of the fistula and its consequences are unknown, and physicians should be aware of these complications. Hysteroscopic follow-up was important in the diagnosis of the two cases.

Stem cells in dermatology.

Preclinical and clinical research have shown that stem cell therapy could be a promising therapeutic option for many diseases in which current medical treatments do not achieve satisfying results or cure. This article describes stem cells sources and their therapeutic applications in dermatology today.

Intrauterine exposure to diesel exhaust diminishes adult ovarian reserve.

OBJECTIVE: To analyze ovarian and uterine morphologic changes resulting from intrauterine and postnatal exposure to diesel exhaust. DESIGN: Crossover study. Experimental groups: intrauterine and postnatal clean air exposure; intrauterine exposure to diesel only; postnatal exposure to diesel only; and intrauterine and postnatal exposure to diesel. SETTING: Laboratory of Experimental Air Pollution. ANIMAL(S): Swiss mice. INTERVENTION(S): Mice exposed to diesel exhaust with doses that correspond to the daily average PM2.5 levels (fine particles in the ambient air 2.5 µm or less in size) reported by the World Health Organization. MAIN OUTCOME MEASURE(S): Morphometric analyses of the ovaries and uterus were performed to define the relative area occupied by follicles, corpus luteum, and stroma and the proportionate area of glands, epithelial layer, and stroma within the uterine endometrium. RESULT(S): A significant reduction in the proportion of primordial follicles was observed in intrauterine-exposed animals, those exposed during the postnatal period, and in animals exposed during both phases. Primary follicle proportion was reduced in animals exposed during pregnancy. No significant changes were detected in uterine morphology. CONCLUSION(S): Intrauterine exposure to acceptable levels of diesel exhaust compromises the reproductive potential of female mice, diminishing ovarian reserve when sexual maturity is achieved. This effect could increase the risk of premature menopause. The findings raise concern about current environmental guidelines for diesel exposure, warranting more careful examination of this issue in humans by regulatory authorities.

Stem cells in dermatology

Preclinical and clinical research have shown that stem cell therapy could be a promising therapeutic option for many diseases in which current medical treatments do not achieve satisfying results or cure. This article describes stem cells sources and their therapeutic applications in dermatology today.

Efeitos intra-uterinos e pós-natais da exposição crônica ao combustível diesel sobre o aparelho reprodutor humano / Intrauterine and postnatal effects of chronic diesel exhaust exposure on the female reproductive tract

INTRODUÇÃO. Os efeitos da poluição atmosférica sobre a saúde humana são cada vez mais reconhecidos. A exposição ao combustível diesel, que contribui significativamente para a poluição em zonas de tráfego veicular intenso, pode ser ao menos parcialmente, responsável por estes efeitos. Estudos epidemiológicos demonstram maior incidência de pré-eclampsia, prematuridade e baixo peso ao nascer. Maiores taxas de falha de implantação e alterações da morfologia placentária são demonstrados em estudos experimentais. OBJETIVO. Análise morfológica do ovário e do útero de camundongos após exposição crônica ao combustível diesel durante a fase intra-uterina e pós-natal. MÉTODO. Estudo experimental prospectivo com crossover. Camundongos foram expostos durante uma hora a doses de combustão do diesel que correspondem a média diária de material particulado fino (MP2.5) recomendado pela Organização Mundial da Saúde (WHO) e a doses acima da média anual recomendada pela mesma. A dose de exposição a MP2.5 foi abaixo da dose recomendada pela Comissão Nacional do Meio Ambiente (CONAMA). Quatro grupos foram formados: animais expostos a ar filtrado no período intra-uterino e no período pós-natal (CC); animais expostos a diesel apenas no período intra-uterino, sendo que no período pós-natal foram expostos a ar filtrado (EC); animais expostos a ar filtrado no período intra-uterino e a diesel no pós-natal (CE), e animais expostos a diesel nos períodos intra-uterino e pós-natal (EE). A análise morfométrica do ovário e do útero foi realizada para definir a área relativa ocupada por cada tipo de folículo, pelo corpo lúteo e pelo estroma, e a proporção de área ocupada por glândulas, estroma e epitélio no endométrio. RESULTADOS. Uma redução significativa de folículos primordiais foi observada em animais expostos a diesel durante o período intra-uterino (p=0,035) e durante o período pós-natal (p=0,015), assim como em animais expostos a diesel nos dois períodos (p=0.004)...

BACKGROUND. There is growing awareness that ambient air pollution compromises human health. Exposure to diesel exhaust, which significantly contributes to pollution in heavy traffic areas, may be at least partially responsible for the observed effects of pollution on human health. Poor reproductive outcomes, such as preeclampsia, preterm deliveries and low birth weight, are described in epidemiological studies. Moreover, experimental evidence shows increased implantation failure rates and placental morphology alterations in exposed mice. OBJECTIVE. The purpose of this study was to analyse ovarian and uterine morphological changes resulting from chronic intrauterine and postnatal exposure to diesel exhaust in mice. METHODS. A experimental prospective crossover study. Mice were exposed to diesel exhaust with doses that correspond to the daily average PM2.5 levels reported by the World Health Organization (WHO) and above the annual average PM2.5 levels. The diesel exhaust exposure doses were also below daily and annual levels recommended by the National Council of Environment (CONAMA). Four groups were examined: intrauterine and postnatal clean, filtered air exposure; intrauterine exposure to diesel only; postnatal exposure to diesel only; and intrauterine and postnatal exposure to diesel. Morphometric analyses of the ovaries and uterus were performed to define the relative area occupied by follicles, corpus luteum and stroma. These analyses also aimed to determine the proportionate area of glands, the epithelial layer and stroma within the uterine endometrium. RESULTS: A significant reduction in primordial follicles was observed in intra-uterine-exposed animals (p=0.035), those exposed during the postnatal period (p=0.015) and in animals exposed during both phases (p=0.004). Primary follicles were reduced in animals exposed during pregnancy (p=0.04). No significant changes were detected in uterine morphology...