scholarly journals Ernest Armstrong McCulloch. 21 April 1926—20 January 2011

2017 ◽  
Vol 64 ◽  
pp. 317-339
Author(s):  
Tak Wah Mak
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Blood Disorders ◽  
Haematopoietic Stem Cells ◽  
Vast Array ◽  
Cellular Physiology ◽  
Haematopoietic Cells ◽  
The World ◽  
Big Picture ◽  
Dual Capacity

Ernest Armstrong McCulloch was half of the brilliant partnership that discovered haematopoietic stem cells (HSCs) and changed how we think about human tissue generation and regeneration. Based at the Ontario Cancer Institute (now the Princess Margaret Cancer Centre) in Toronto, the haematologist ‘Bun’ McCulloch, together with James E. Till, a physicist with a steel-trap mind, exercised their penchant for adventurous ‘big picture’ thinking in devising experiments to identify stem cells. This exceptional team was the first to demonstrate that HSCs have the dual capacity to self-renew and to differentiate into a vast array of mature haematopoietic cells. Their trainees, as well as investigators elsewhere, built on McCulloch and Till's findings not only to isolate and characterize HSCs and progenitors derived from them, but also to devise therapies for certain blood disorders. Later in his career, Ernest focused on characterizing the malignant cells of human leukaemias and determining the effects of various drugs on leukaemic cell growth. The implications of Till and McCulloch's work continue to be profound and underpin many significant breakthroughs in our knowledge of normal cellular physiology, pathophysiology, tumorigenesis and tissue transplantation. Indeed, regenerative medicine owes its very existence to the stem cell discoveries of McCulloch, Till and others. At times eccentric and demanding, but always well spoken, incisive and erudite, Ernest personified the outstanding research scientist cloaked in Canadian modesty. His legacy lives on in the bright therapeutic future emerging from the rigorous stem cell research being conducted in Canada and around the world.

scholarly journals Expanded mesenchymal stem cell transplantation is safe in both local injection and vein transfusion

2017 ◽  
Vol 4 (3-4) ◽  
pp. 234-235 ◽  
Author(s):  
Vlassov V Salval ◽  
Yone Moto
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Stem Cell ◽  
Clinical Applications ◽  
Local Injection ◽  
Mesenchymal Stem Cell Transplantation ◽  
Routine Treatment ◽  
Drug Products ◽  
The World

More than 500 clinical trials are using mesenchymal stem cells (MSCs) in the world to treat some different diseases. The safety of expanded MSC transplantation is the most important thing to ensure that this therapy can become the routine treatment for human diseases. More than five MSCs based stem cell drug products are approved at various countries demonstrated that expanded MSCs are safe in both local injection and transfusion. Moreover, some recent reports for 5 and 10 years followed-up clinical trials using expanded MSCs confirmed that there is not different tumorigenesis between the patients with and without expanded MSC transplantation. This letter aims to provide some evidences about the safety of expanded MSCs in clinical applications. However, the MSC quality should be stritcly controlled during the in vitro MSC expansion.

scholarly journals Single Cell Phenotyping Reveals Heterogeneity among Haematopoietic Stem Cells Following Infection

2016 ◽  
Author(s):  
Adam L MacLean ◽  
Maia A Smith ◽  
Juliane Liepe ◽  
Aaron Sim ◽  
Reema Khorshed ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Single Cell ◽  
Life History Theory ◽  
Cell Function ◽  
Trichinella Spiralis ◽  
Haematopoietic Stem Cell ◽  
Haematopoietic Stem Cells ◽  
Hsc Niche

AbstractThe haematopoietic stem cell (HSC) niche provides essential micro-environmental cues for the production and maintenance of HSCs within the bone marrow. During inflammation, haematopoietic dynamics are perturbed, but it is not known whether changes to the HSC-niche interaction occur as a result. We visualise HSCs directly in vivo, enabling detailed analysis of the 3D niche dynamics and migration patterns in murine bone marrow following Trichinella spiralis infection. Spatial statistical analysis of these HSC trajectories reveals two distinct modes of HSC behaviour: (i) a pattern of revisiting previously explored space, and (ii) a pattern of exploring new space. Whereas HSCs from control donors predominantly follow pattern (i), those from infected mice adopt both strategies. Using detailed computational analyses of cell migration tracks and life-history theory, we show that the increased motility of HSCs following infection can, perhaps counterintuitively, enable mice to cope better in deteriorating HSC-niche micro-environments following infection.Author SummaryHaematopoietic stem cells reside in the bone marrow where they are crucially maintained by an incompletely-determined set of niche factors. Recently it has been shown that chronic infection profoundly affects haematopoiesis by exhausting stem cell function, but these changes have not yet been resolved at the single cell level. Here we show that the stem cell–niche interactions triggered by infection are heterogeneous whereby cells exhibit different behavioural patterns: for some, movement is highly restricted, while others explore much larger regions of space over time. Overall, cells from infected mice display higher levels of persistence. This can be thought of as a search strategy: during infection the signals passed between stem cells and the niche may be blocked or inhibited. Resultantly, stem cells must choose to either ‘cling on’, or to leave in search of a better environment. The heterogeneity that these cells display has immediate consequences for translational therapies involving bone marrow transplant, and the effects that infection might have on these procedures.

Transcriptional Regulation of the LMO2 T-Cell Leukaemia Oncogene.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2728-2728
Author(s):  
Josette-Renée Landry ◽  
Sarah Kinston ◽  
Kathy Knezevic ◽  
Anthony R. Green ◽  
Berthold Göttgens
Keyword(s):  
Stem Cells ◽  
T Cell ◽  
Cell Lines ◽  
Molecular Mechanisms ◽  
Regulatory Elements ◽  
Proximal Promoter ◽  
Cell Leukaemia ◽  
Haematopoietic Stem Cells ◽  
Haematopoietic Cells

Abstract Transcriptional control has long been identified as a key mechanism regulating the formation and subsequent behaviour of haematopoietic stem cells. We have used a comparative genomics approach to identify transcriptional regulatory elements of the LMO2 gene, a transcriptional cofactor originally identified through its involvement in T-cell leukaemia and subsequently shown to be critical for the formation of haematopoietic stem cells and endothelial development. An initial stringent search for homology between evolutionary distant species demonstrated that, apart from the coding exons, high level of identity between mammalian, amphibian and fish sequences was restricted to the proximal promoter region of LMO2. Real-time RT-PCR expression analysis identified this promoter as the predominant source of transcription in haematopoietic tissue. Transient and stable transfections indicated that the proximal promoter was active in haematopoietic progenitor and endothelial cell lines and this activity was shown to depend on three conserved Ets sites which were bound in vivo by Elf1, Fli1 and Ets1. Transgenic analysis demonstrated that the LMO2 proximal promoter was sufficient for expression in endothelial cells in vivo. However, no haematopoietic expression was observed indicating that additional enhancers are required to mediate transcription from the proximal promoter in haematopoietic cells. To identify additional elements involved in haematopoietic expression of LMO2, we have performed a less restrictive search for conserved sequences by comparing the human, dog, rat and mouse LMO2 loci to the marsupial opossum LMO2 locus. The addition of the opossum locus, and removal of the more distant fish and amphibian sequences from the alignment, resulted in the discovery of eleven conserved regions. These sequences represent candidate haematopoietic regulatory regions as they contain conserved transcription factor binding sites (E boxes, Ets and Gata sites) previously shown to regulate several other haematopoietic genes. We will present results from a systematic analysis of these regions for enhancer activity in both haematopoietic cell lines and transgenic mice, which suggest that several of these elements indeed act as enhancers. Taken together, our experiments will provide a framework for the transcriptional hierarchies within which LMO2 exerts its function in normal haematopoietic cells. Moreover, the current studies will serve as a platform to examine potential molecular mechanisms that can cause ectopic expression of LMO2 in T-cell progenitors with the ultimate consequence of developing T-ALL.

scholarly journals An evolution of stem cell research and therapy in Viet Nam

2018 ◽  
Vol 5 (1) ◽  
Author(s):  
Phuc Van Pham ◽  
Ngoc Bich Vu ◽  
Oanh Thuy Huynh ◽  
Mai Thi-Hoang Truong ◽  
Truc Le-Buu Pham ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Stem Cell Research ◽  
Web Of Science ◽  
Scientific Information ◽  
Clinical Applications ◽  
Viet Nam ◽  
Disease Treatment ◽  
Research Activities ◽  
The World

Stem cell research and therapy are one of the most attractive studies in the biomedicine. Not only in the bench, nowadays stem cells but also become the bustling industry. In Vietnam, biomedical scientists started to study and apply stem cells since 1995. From that, Vietnamese scientists got some significant achievements in stem cell research and therapy, especially in stem cell therapy for disease treatment. This report aimed to provide an overview of stem cell research and therapy from 1995 to date. Stem cell research activities were collected and analyzed based on the publications, projects about stem cells in some databases including Web of Science, Google Scholar, Embase, and national scientific information. The results showed that stem cell research and therapy significantly increased from 2009 to date with more publications about stem cells and more clinical applications. With this growth rate, we hope that Vietnam can develop the stem cell industry and become one the stem cell center in the Asian and the world.

scholarly journals A Mini Review Focused on the Recent Applications of Graphene Oxide in Stem Cell Growth and Differentiation

2018 ◽  
Author(s):  
Alexander Halim ◽  
Qing Luo ◽  
Yang Ju ◽  
Guanbin Song
Keyword(s):  
Stem Cells ◽  
Graphene Oxide ◽  
Stem Cell ◽  
Cell Growth ◽  
Disease Modeling ◽  
Biological Effects ◽  
Stem Cell Differentiation ◽  
Differentiation Potential ◽  
The World ◽  
Cell Growth And Differentiation

Stem cells are undifferentiated cells which can give rise to any types of cells in our body. Hence, they have been utilized for various applications such as drug testing and disease modeling. However, for the successful of those applications, the survival and differentiation of stem cells into specialized lineages should be well controlled. Growth factors and chemical agents are the most common signals to promote the proliferation and differentiation of stem cells. However, those approaches holds several drawbacks such as the negative side effects, degradation or denaturation, and expensive. To address such limitations, nanomaterials have been recently used as a better approach for controlling stem cells behaviors. Graphene oxide is the derivative of graphene, the first 2D materials in the world. Recently, due to its extraordinary properties and great biological effects on stem cells, many scientists around the world have utilized graphene oxide to enhance the differentiation potential of stem cells. In this mini review, we highlight the key advances about the effects of graphene oxide on controlling stem cell growth and various types of stem cell differentiation. We also discuss the possible molecular mechanisms of graphene oxide in controlling stem cell growth and differentiation.

scholarly journals The Detailed Study of CD10: A Stromal Marker in Breast Carcinoma

2021 ◽  
pp. 62-70
Author(s):  
Huidrom Jyotsna Devi ◽  
P. Karkuzhali ◽  
P. K. Baskaran ◽  
S. Mary Lilly
Keyword(s):  
Public Health ◽  
Breast Cancer ◽  
Stem Cells ◽  
Stem Cell ◽  
Breast Carcinoma ◽  
Cell Surface ◽  
Acute Lymphoblastic Leukaemia ◽  
Lymphoblastic Leukaemia ◽  
The World ◽  
Apocrine Sweat Gland

Breast carcinoma is one of the most frequently occurring cancers among women with one million cases. Breast cancer is the primary cause of death in women around the world. It is one of the major concerns in public health due to its high occurrence and growing tendency.   This complex functional structure develops from a highly modified apocrine sweat gland in the female, but remains rudimentary in male. Breast develops embryological into two lines along milk lines extending from axilla to groin. CD-10 is a 90- to 110-kDa cell surface zinc dependent metalloproteinase which is known as “Common Acute Lymphoblastic Leukaemia Antigen” (CALLA). CD-10 acts  as a stem cell regulator in the breast and  prevents uncontrolled proliferation on stem cells The present study is designed to study the expression of CD-10, a breast carcinoma stromal marker and its correlation with ER, PR and HER2/neu status in breast carcinoma.

scholarly journals A Mini Review Focused on the Recent Applications of Graphene Oxide in Stem Cell Growth and Differentiation

Nanomaterials ◽  
2018 ◽  
Vol 8 (9) ◽  
pp. 736 ◽  
Author(s):  
Alexander Halim ◽  
Qing Luo ◽  
Yang Ju ◽  
Guanbin Song
Keyword(s):  
Stem Cells ◽  
Graphene Oxide ◽  
Stem Cell ◽  
Cell Growth ◽  
Disease Modeling ◽  
Biological Effects ◽  
Stem Cell Differentiation ◽  
Differentiation Potential ◽  
The World ◽  
Cell Growth And Differentiation

Stem cells are undifferentiated cells that can give rise to any types of cells in our body. Hence, they have been utilized for various applications, such as drug testing and disease modeling. However, for the successful of those applications, the survival and differentiation of stem cells into specialized lineages should be well controlled. Growth factors and chemical agents are the most common signals to promote the proliferation and differentiation of stem cells. However, those approaches holds several drawbacks such as the negative side effects, degradation or denaturation, and expensive. To address such limitations, nanomaterials have been recently used as a better approach for controlling stem cells behaviors. Graphene oxide is the derivative of graphene, the first two-dimensional (2D) materials in the world. Recently, due to its extraordinary properties and great biological effects on stem cells, many scientists around the world have utilized graphene oxide to enhance the differentiation potential of stem cells. In this mini review, we highlight the key advances about the effects of graphene oxide on controlling stem cell growth and various types of stem cell differentiation. We also discuss the possible molecular mechanisms of graphene oxide in controlling stem cell growth and differentiation.

Stem Cells: A Golden Therapy for Diabetic Wound

2020 ◽  
Vol 16 ◽  
Author(s):  
Shubhangi Buchade ◽  
Shivani Desai ◽  
Ramesh Bhonde ◽  
Heena Kazi ◽  
Shivani Sainani ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Stem Cells ◽  
Stem Cell ◽  
Microvascular Complications ◽  
Foot Ulcer ◽  
Major Complication ◽  
Diabetic Wound ◽  
Organ Systems ◽  
The World

: Diabetes mellitus is the 7 th leading cause of death worldwide. Diabetes can affect the organ systems and lead to serious complication, majorly categorized as macrovascular complications, microvascular complications, and diabetic wound. Foot ulcer develops in 15-25% diabetic patient. In diabetic wound there is impairment in growth factor, neuropeptide, matrix metalloproteinases, angiogenesis, immune system. Many approaches are being experimented to manage this major complication of diabetic foot, but unfortunately with lesser success rate. Stem cell is an upcoming field which is being explored in the world of diabetes. Hence, this review is designed to understand the basic pathogenesis and complications of types of diabetes and the role of stem cells in diabetic wound and the benefits related to it.

Inactivation of p38 MAPK Extends Self-Renewal Capacity of Haematopoietic Stem Cells.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 265-265
Author(s):  
Keisuke Ito ◽  
Atsushi Hirao ◽  
Fumio Arai ◽  
Sahoko Matsuoka ◽  
Keiyo Takubo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
P38 Mapk ◽  
Cell Population ◽  
Critical Role ◽  
Dependent Manner ◽  
Self Renewal ◽  
Haematopoietic Stem Cells ◽  
P38 Inhibitor

Abstract Haematopoietic stem cells (HSCs) undergo self-renewing cell divisions and maintain blood production for their lifetime. Appropriate control of HSC self-renewal is critical for maintenance of haematopoietic homeostasis. Here we show that activation of p38 MAPK limits lifespan of HSCs in response to increasing levels of reactive oxygen species (ROS) in vivo. Although normal quiescent HSCs maintain a low level of oxidative stress, an increase in ROS was observed in HSCs after transplantation as well as in aged mice. In vitro treatment with BSO (Buthionine sulfoximine), which depletes intra-cellular glutathion, increased ROS (H2O2) level in immature hematopoietic cell population, c-kit+Sca1+Lin- (KSL) cells, in a dose-dependent manner. Low dose concentration of BSO suppressed reconstitution capacity of HSCs, whereas higher concentration did not affect progenitors. These data indicate that HSCs are much more sensitive to increased ROS than progenitors and are consistent with our previous results from Atm−/− mice in which ROS level is elevated in vivo. Here we focused on MAPKs for the stem cell dysfunction since it has been shown that several MAPKs are activated in response to ROS. We evaluated effects of MAPK inhibitors for p38, JNK or ERK in incubation of KSL cell with BSO. p38 inhibitor (SB203580), neither JNK nor ERK inhibitor, restored reconstitution capacity of HSCs after transplantation, suggesting that activation of p38 may contributes to defect of stem cell function in vivo. To address the question, we evaluated p38 activation in Atm−/− BM cells by immunohistochemistry. Surprisingly, p38 protein was phosphorylated only in KSL cells, but not other more differentiated cell populations, despite that the ROS levels were comparable among the cell population of mice. In response to activation of p38, p16INK4a was up-regulated only in KSL cells. The data indicates a possibility that stem cell-specific p38 activation negatively regulates self-renewal of HSCs. We then investigated a role of p38 activation on self-renewal of HSCs in vivo. When p38 inhibitor was intraperitoneally administered both before and after BMT, the level of repopulation achieved was comparable to that of the wild-type. Furthermore, Atm−/− mice that received long-term p38 inhibitor treatment did not show either anemia, a decrease in progenitor colony-forming capacity, or reduced frequencies of stem cell subsets. These data demonstrate that the activation of p38 present in HSCs promotes the exhaustion of stem cell pool in response to elevation of ROS. It has been proposed that aging is driven in part by a gradual depletion of stem cell functional capacity. There are evidences that inappropriate production of oxidants is connected to aging and life span. We propose a possibility that p38 activation in response to ROS plays a critical role for limit of stem cell capacity.

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