American journal of stem cells最新文献

The successful generation of the first iPSCs about ten years ago has provided deeper insight into previously unknown disease mechanisms and therapeutic opportunities for many diseases. In particular, iPSCs are becoming an important tool in advancing modeling and therapeutic intervention for Alzheimer's disease. In this manuscript, we assess the research climate surrounding the application of iPSCs to familial and sporadic Alzheimer's disease, including the generation and isolation of individualized neural stem cells, the introduction of neural stem cell transplants using iPSCs, and an estimation of the potential use of iPSCs as research models for Alzheimer's treatments and therapies. The clinical application of stem cells in the treatment of Alzheimer's disease appears promising, but much of the recent experimentation has been conducted using animal models or embryonic stem cells. As induced pluripotent stem cell research advances, iPSCs will likely provide investigators with a more applicable tool to progress advances in research and treatment for Alzheimer's and other neurodegenerative diseases.

Although umbilical cord blood (UCB) hematopoietic stem cell transplantation (UCBT) has emerged as a promising haematological reconstitution therapy for leukemias and other related disorders, the insufficient UCB stem cell dosage still hinders better clinical outcomes. Previous research efforts, by focusing on ex vivo UCB expansion capabilities have sought to benefit from well-known mechanisms of self-renewal characteristics of UCB stem cells. However, the long-term (> 21 days) in vitro culture period and the low neutrophil recovery significantly reduce the transplantability of such ex vivo expanded UCB stem cells. To overcome the latter hurdles in this study, a post-thaw, short-term ex vivo expansion methodology of UCB mononuclear (UCB-MN) and CD34(+) cells has been established. Notably, such effort was achieved through pharmacological preconditioned of UCB cultures by filgrastim agent already used in the clinical setting. In crucial cell populations implicated in the promotion of functional engraftment, the progression of free survival rates (PFS), a marked increase of 6.65 to 9.34 fold for UCB-MN and 35 to 49 fold for CD34(+) cells has been noticed. Overall, these results indicate that transplantation of pharmacologically-preconditioned ex vivo expansion of UCB stem and progenitor cells keep high promise upon transplantation to enhance therapeutic potential in everyday clinical practice.

Acute kidney injury (AKI) is the rapid onset of decreased kidney function that ultimately increases mortality and morbidity. Stem cell research is a promising avenue for curative and preventative therapies of kidney injury, however, there are many types of stem cells under investigation. Currently there is no research to compare the value of one stem cell method over another. Induced pluripotent stem cells (iPSCs) and spermatogonial stem cells (SSCs) have been shown to differentiate into renal cells, though further clinical research is needed to fully explore potential therapeutic strategies. Mesenchymal stem cells (MSCs) have long been investigated in the preclinical setting and have recently been successful in Phase I clinical trials. MSCs may represent a promising new therapeutic approach to treat AKI as they demonstrate renoprotective effects post-injury via the secretion of promitotic, anti-apoptotic, anti-inflammatory, and immunomodulatory factors. Given the most current research, MSCs appear to offer a promising course of treatment for AKI.

Historically, research into congenital defects has focused on maternal impacts on the fetal genome during gestation and prenatal periods. However, recent findings have sparked interest in epigenetic alterations of paternal genomes and its effects on offspring. This emergent field focuses on how environmental influences can epigenetically alter gene expression and ultimately change the phenotype and behavior of progeny. There are three primary mechanisms implicated in these changes: DNA methylation, histone modification, and miRNA expression. This paper provides a summary and subsequent review of past research, which highlights the significant impact of environmental factors on paternal germ cells during the lifetime of an individual as well as those of future generations. These findings support the existence of transgenerational epigenetic inheritance of paternal experiences. Specifically, we explore epidemiological and laboratory studies that demonstrate possible links between birth defects and paternal age, environmental factors, and alcohol consumption. Ultimately, our review highlights the clinical importance of these factors as well as the necessity for future research in the field.

Hearing impairment most often involves loss of sensory hair cells and auditory neurons. As this loss is permanent in humans, a cell therapy approach has been suggested to replace damaged cells. It is thus of interest to generate lineage restricted progenitor cells appropriate for cell based therapies. Human long-term self-renewing neuroepithelial stem (lt-NES) cell lines exhibit in vitro a developmental potency to differentiate into CNS neural lineages, and importantly lack this potency in vivo, i.e do not form teratomas. Small-molecules-driven differentiation is today an established route obtain specific cell derivatives from stem cells. In this study, we have investigated the effects of three small molecules SB431542, ISX9 and Metformin to direct differentiation of lt-NES cells into sensory neurons. Exposure of lt-NES cells to Metformin or SB431542 did not induce any marked induction of markers for sensory neurons. However, a four days exposure to the ISX9 small molecule resulted in reduced expression of NeuroD1 mRNA as well as enhanced mRNA levels of GATA3, a marker and important player in auditory neuron specification and development. Subsequent culture in the presence of the neurotrophic factors BDNF and NT3 for another seven days yielded a further increase of mRNA expression for GATA3. This regimen resulted in a frequency of up to 25-30% of cells staining positive for Brn3a/Tuj1. We conclude that an approach with ISX9 small molecule induction of lt-NES cells into auditory like neurons may thus be an attractive route for obtaining safe cell replacement therapy of sensorineural hearing loss.

Pulmonary artery remodelling it is a major feature of pulmonary hypertension (PH). It is characterised by cellular and structural changes of the pulmonary arteries causing higher pulmonar vascular resistance and right ventricular failure. Abnormal deposition of smooth muscle-like (SM-like) cells in normally non-muscular, small diameter vessels and a deregulated control of endothelial cells are considered pathological features of PH. The origin of the SM-like cells and the mechanisms underlying the development and progression of this remodelling process are not understood. Endothelial cells within the intima may migrate from their organised layer of cells and transition to mesenchymal or SM-like phenotype in a process called endothelial-mesenchymal transition (EnMT). Traditionally, Waddington's epigenetic landscape illustrates that fates of somatic cells are progressively determined to compulsorily follow a downhill differentiation pathway. EnMT induces the transformation of cells with stem cell traits, therefore contrasting Waddington's theory and confirming that cell fate seems to be far more flexible than previously thought. The prospect of therapeutic inhibition of EnMT to delay or prevent PH may represent a promising new treatment modality.

Amyotrophic Lateral Sclerosis (ALS) is a rapidly progressive neurodegenerative disorder with fatal prognosis. Cellular therapy has been studied for ALS in various animal models and these advances have highlighted its potential to be a treatment modality. This is a retrospective controlled cohort study of total 57 patients. Out of these, 37 patients underwent autologous bone marrow mononuclear cell transplantation in addition to standard rehabilitation and Riluzole. Control group consisted of 20 patients who did not receive cell transplantation. The survival duration since the onset of the disease for both the groups was computed using a Kaplan-Meier Survival analysis and compared using log-rank test. Effect of age at onset, type of onset and lithium on survival duration in the intervention group was analyzed. Mean survival duration of patients in intervention group was 87.76 months which was higher than the control group mean survival duration of 57.38 months. Survival duration was significantly (p = 0.039) higher in people with the onset of the disease below 50 years of age. Limb onset and lithium also showed positive influence on the survival duration. Mean survival duration of the intervention group was also higher than the survival duration of ALS patients in previous epidemiological studies. In addition to the standard treatment with Riluzole, early intervention with combination of BMMNCs transplantation and Lithium may have a positive effect on the survival duration in ALS. Prospective randomized controlled studies with a larger sample size and rigorous methodology are required for conclusive findings.

Adipose tissue derived stem cells (ASCs) are mesenchymal stem cells which can be obtained from different adipose tissue sources within the body. It is an abundant cell pool, which is easy accessible and the cells can be obtained in large numbers, cultivated and expanded in vitro and prepared for tissue engineering approaches, especially for skeletal tissue repair. In the recent years this cell population has attracted a great amount of attention among researchers in human as well as in veterinary medicine. In the meantime ASCs have been well characterized and their use in regenerative medicine is very well established. This review focuses on the characterization of ASCs for their use for tissue engineering approaches especially in veterinary medicine and also highlights a selection of clinical trials on the basis of ASCs as the relevant cell source.