Talk:Stem Cells 1

From CellBiology


Pluripotent stem cells progressing to the clinic


PMID 26908143


Stability of genomic imprinting in human induced pluripotent stem cells

BMC Genet. 2013 Apr 30;14(1):32. [Epub ahead of print]

Hiura H, Toyoda M, Okae H, Sakurai M, Miyauchi N, Sato A, Kiyokawa N, Okita H, Miyagawa Y, Akutsu H, Nishino K, Umezawa A, Arima T.


BACKGROUND: hiPSCs are generated through epigenetic reprogramming of somatic tissue. Genomic imprinting is an epigenetic phenomenon through which monoallelic gene expression is regulated in a parent-of-origin-specific manner. Reprogramming relies on the successful erasure of marks of differentiation while maintaining those required for genomic imprinting. Loss of imprinting (LOI), which occurs in many types of malignant tumors, would hinder the clinical application of hiPSCs. RESULTS: We examined the imprinting status, expression levels and DNA methylation status of eight imprinted genes in five independently generated hiPSCs. We found a low frequency of LOI in some lines. Where LOI was identified in an early passage cell line, we found that this was maintained through subsequent passages of the cells. Just as normal imprints are maintained in long-term culture, this work suggests that abnormal imprints are also stable in culture. CONCLUSIONS: Analysis of genomic imprints in hiPSCs is a necessary safety step in regenerative medicine, with relevance both to the differentiation potential of these stem cells and also their potential tumorigenic properties.

PMID 23631808

Insights and hopes in umbilical cord blood stem cell transplantations

J Biomed Biotechnol. 2012;2012:572821. doi: 10.1155/2012/572821. Epub 2012 Oct 31.

Shahrokhi S, Menaa F, Alimoghaddam K, McGuckin C, Ebtekar M. Source Department of Immunology, School of Medicine, Lorestan University of Medical Sciences, Khorramabad 381351698, Iran. Abstract

Over 20.000 umblical cord blood transplantations (UCBT) have been carried out around the world. Indeed, UCBT represents an attractive source of donor hematopoietic stem cells (HSCs) and, offer interesting features (e.g., lower graft-versus-host disease) compared to bone marrow transplantation (BMT). Thereby, UCBT often represents the unique curative option against several blood diseases. Recent advances in the field of UCBT, consisted to develop strategies to expand umbilical stem cells and shorter the timing of their engraftment, subsequently enhancing their availability for enhanced efficacy of transplantation into indicated patients with malignant diseases (e.g., leukemia) or non-malignant diseases (e.g., thalassemia major). Several studies showed that the expansion and homing of UCBSCs depends on specific biological factors and cell types (e.g., cytokines, neuropeptides, co-culture with stromal cells). In this review, we extensively present the advantages and disadvantages of current hematopoietic stem cell transplantations (HSCTs), compared to UBCT. We further describe the importance of cord blood content and obstetric factors on cord blood selection, and report the recent approaches that can be undertook to improve cord blood stem cell expansion as well as engraftment. Eventually, we provide two majors examples underlining the importance of UCBT as a potential cure for blood diseases.

PMID 23258957 [PubMed - indexed for MEDLINE] PMCID: PMC3509718

Development of new technologies for stem cell research

J Biomed Biotechnol. 2012;2012:741416. doi: 10.1155/2012/741416. Epub 2012 Nov 26.

Ma X, Zhang Q, Yang X, Tian J. Source Intelligent Medical Research Center, State Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China. Abstract Since the 1960s, the stem cells have been extensively studied including embryonic stem cells, neural stem cells, bone marrow hematopoietic stem cells, and mesenchymal stem cells. In the recent years, several stem cells have been initially used in the treatment of diseases, such as in bone marrow transplant. At the same time, isolation and culture experimental technologies for stem cell research have been widely developed in recent years. In addition, molecular imaging technologies including optical molecular imaging, positron emission tomography, single-photon emission computed tomography, and computed tomography have been developed rapidly in recent the 10 years and have also been used in the research on disease mechanism and evaluation of treatment of disease related with stem cells. This paper will focus on recent typical isolation, culture, and observation techniques of stem cells followed by a concise introduction. Finally, the current challenges and the future applications of the new technologies in stem cells are given according to the understanding of the authors, and the paper is then concluded. PMID 23251081

Concise review: self-renewal in the central nervous system: neural stem cells from embryo to adult

Stem Cells Transl Med. 2012 Apr;1(4):298-308. doi: 10.5966/sctm.2011-0045. Epub 2012 Apr 10.

De Filippis L, Binda E. Source Department of Biotechnology and Biosciences, University of Milan-Bicocca, Italy. Abstract The recent discovery of neural stem cells (NSCs) in the adult mammalian brain has fostered a plethora of translational and preclinical studies to investigate future therapeutic approaches for the cure of neurodegenerative diseases. These studies are finally at the clinical stage, and some of them are already under way. The definition of a bona fide stem cell has long been the object of much debate focused on the establishment of standard and univocal criteria to distinguish between stem and progenitor cells. It is commonly accepted that NSCs have to fulfill two basic requirements, the capacity for long-term self-renewal and the potential for differentiation, which account for their physiological role, namely central nervous system tissue homeostasis. Strategies such as immortalization or reprogramming of somatic cells to the embryonic-like stage of pluripotency indicate the relevance of extensive self-renewal ability of NSCs either in vitro or in vivo. Moreover, the discovery of stem-like tumor cells in brain tumors, such as gliomas, accompanied by the isolation of these cells through the same paradigm used for related healthy cells, has provided further evidence of the key role that self-renewal plays in the development and progression of neurodegenerative diseases and cancer. In this review we provide an overview of the current understanding of the self-renewal capacity of nontransformed human NSCs, with or without immortalization or reprogramming, and of stem-like tumor cells, referring to both research and therapeutic studies. PMID 23197809

Embryonic stem cell-derived trophoblast differentiation: a comparative review of the biology, function, and signaling mechanisms

J Endocrinol. 2013 Feb 25;216(3):R33-45. doi: 10.1530/JOE-12-0433. Print 2013 Mar.

Giakoumopoulos M, Golos TG. Source Wisconsin National Primate Research Center, Department of Obstetrics and Gynecology, University of Wisconsin-Madison, 1223 Capitol Court, Madison, Wisconsin 53715-1299, USA.

Abstract The development of the placenta is imperative for successful pregnancy establishment, yet the earliest differentiation events of the blastocyst-derived trophectoderm that forms the placenta remain difficult to study in humans. Human embryonic stem cells (hESC) display a unique ability to form trophoblast cells when induced to differentiate either by the addition of exogenous BMP4 or by the formation of cellular aggregates called embryoid bodies. While mouse trophoblast stem cells (TSC) have been isolated from blastocyst outgrowths, mouse ESC do not spontaneously differentiate into trophoblast cells. In this review, we focus on addressing the similarities and differences between mouse TSC differentiation and hESC-derived trophoblast differentiation. We discuss the functional and mechanistic diversity that is found in different species models. Of central importance are the unique signaling events that trigger downstream gene expression that create specific cellular fate decisions. We support the idea that we must understand the nuances that hESC differentiation models display so that investigators can choose the appropriate model system to fit experimental needs.

PMID 23291503

Safety of cell therapy with mesenchymal stromal cells (SafeCell): a systematic review and meta-analysis of clinical trials

PLoS One. 2012;7(10):e47559. doi: 10.1371/journal.pone.0047559. Epub 2012 Oct 25.

Lalu MM, McIntyre L, Pugliese C, Fergusson D, Winston BW, Marshall JC, Granton J, Stewart DJ; Canadian Critical Care Trials Group. Source Department of Anesthesiology, University of Ottawa, Ottawa, Canada.

Abstract BACKGROUND: Mesenchymal stromal cells (MSCs, "adult stem cells") have been widely used experimentally in a variety of clinical contexts. There is interest in using these cells in critical illness, however, the safety profile of these cells is not well known. We thus conducted a systematic review of clinical trials that examined the use MSCs to evaluate their safety. METHODS AND FINDINGS: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (to June 2011), were searched. Prospective clinical trials that used intravascular delivery of MSCs (intravenously or intra-arterially) in adult populations or mixed adult and pediatric populations were identified. Studies using differentiated MSCs or additional cell types were excluded. The primary outcome adverse events were grouped according to immediate events (acute infusional toxicity, fever), organ system complications, infection, and longer term adverse events (death, malignancy). 2347 citations were reviewed and 36 studies met inclusion criteria. A total of 1012 participants with clinical conditions of ischemic stroke, Crohn's disease, cardiomyopathy, myocardial infarction, graft versus host disease, and healthy volunteers were included. Eight studies were randomized control trials (RCTs) and enrolled 321 participants. Meta-analysis of the RCTs did not detect an association between acute infusional toxicity, organ system complications, infection, death or malignancy. There was a significant association between MSCs and transient fever. CONCLUSIONS: Based on the current clinical trials, MSC therapy appears safe. However, further larger scale controlled clinical trials with rigorous reporting of adverse events are required to further define the safety profile of MSCs.

PMID 23133515