Side population (SP) cells are an enriched population of stem, and the existence of SP cells has been reported in human cancer cell lines. In this study, we performed an SP analysis using 11 human cancer cell lines and confirmed the presence of SP cells in an embryonic carcinoma cell line, NEC8. NEC8 SP cells showed characteristics of cancer stem cells, such as high growth rate, chemoresistance and high invasiveness. To further characterize the NEC8 SP cells, we used DNA microarrays. Among 38,500 genes, we identified 12 genes that were over-expressed in SP cells and 1 gene that was over-expressed in non-SP cells. Among these 13 genes, we focused on GADD45b. GADD45b was over-expressed in non-SP cells, but the inhibition of GADD45b had no effect on non-SP cells. Paradoxically, the inhibition of GADD45b significantly reduced the viability of NEC8 SP cells. The inhibition of ABCG2, which determines the SP phenotype, had no effect on the invasiveness of NEC8 SP cells, but the inhibition of GADD45b significantly reduced invasiveness. These results suggest that GADD45b, but not ABCG2, might determine the cancer stem cell-like phenotype, such as chemoresistance and the high invasiveness of NEC8 SP cells, and might be a good therapeutic target.

Toshihiko Inowa

Keiichi Hishikawa

Yumi Matsuzaki

Takayuki Isagawa

Takumi Takeuchi

Hiroyuki Aburatani

Tadaichi Kitamura

Toshiro Fujita

GADD45<svg style="vertical-align:-3.56265pt" height="16.6625" version="1.1" viewBox="0 0 10 16.6625" width="10" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
		<g transform="matrix(.017,-0,0,-.017,.062,12.162)">
			<path id="x1D6FD" d="M558 587q0 -32 -14 -61t-40 -53.5t-48.5 -41t-54.5 -36.5q144 -51 144 -174q0 -55 -43.5 -108t-104.5 -87q-77 -42 -131 -42q-31 0 -54 20t-31 47l11 18q48 -29 108 -29q79 0 119.5 43t40.5 109t-44.5 107.5t-119.5 50.5l22 47q34 1 65 21q96 61 96 157q0 42 -24 67.5
t-62 25.5q-24 0 -43.5 -9t-35 -29.5t-27 -44t-22.5 -63t-19.5 -75.5t-18.5 -91q-57 -294 -68 -380q-26 -190 -35 -200q-26 -31 -97 -37l-4 26q19 9 48 170l77 413q23 121 52.5 187.5t83.5 114.5q70 62 148 62q51 0 88.5 -34t37.5 -91z"/>
		</g>
	</svg> Determines Chemoresistance and Invasive Growth of Side Population Cells of Human Embryonic Carcinoma

Bone marrow-derived mesenchymal stem cells (BMDMSC) are emerging as a therapeutic modality in various inflammatory disease states, including acute lung injury (ALI). A hallmark of inflammation, and a consistent observation in patients with ALI, is a perturbation in the systemic redox environment. However, little is known about the effects of BMDMSC on the systemic redox status. The objective of the present study was to determine whether exogenously infused BMDMSC protect against endotoxin-induced oxidation of plasma cysteine (Cys) and glutathione (GSH) redox states. To determine the effect on the redox state if BMDMSC, mice received endotoxin intraperitoneally (1 mg/kg), followed by intravenous infusion of either <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mn>5</mml:mn><mml:mo>×</mml:mo><mml:msup><mml:mn>10</mml:mn><mml:mn>5</mml:mn></mml:msup></mml:math> BMDMSC or an equal volume of saline solution. Control mice received intraperitoneal endotoxin followed by <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mn>5</mml:mn><mml:mo>×</mml:mo><mml:msup><mml:mn>10</mml:mn><mml:mn>5</mml:mn></mml:msup></mml:math> lung fibroblasts given intravenously. Cys, cystine (CySS), GSH, and glutathione disulfide (GSSG) concentrations were determined by HPLC. Results showed sequential preservation of plasma Cys and GSH levels in response to BMDMSC infusion. The data show that BMDMSC infusion leads to a more reducing Cys and GSH redox state. The findings are the first to demonstrate that BMDMSC have antioxidant effects in vivo, and add to our understanding of the systemic effects of BMDMSC in lung injury.

Smita S. Iyer

Edilson Torres-Gonzalez

David C. Neujahr

Mike Kwon

Kenneth L. Brigham

Dean P. Jones

Ana L. Mora

Mauricio Rojas

Effect of Bone Marrow-Derived Mesenchymal Stem Cells on Endotoxin-Induced Oxidation of Plasma Cysteine and Glutathione in Mice

The limited availability of cadaveric human donor pancreata as well as the incomplete success of the Edmonton protocol for human islet allografts fasten search for new sources of insulin the producing cells for substitution cell therapy of insulin-dependent diabetes mellitus (T1DM). Starting from isolated neonatal porcine pancreatic islets (NPIs), we have obtained cell monolayers that were exposed to microencapsulated monolayered Sertoli cells (ESCs) for different time periods (7, 14, 21 days). To assess the development of the cocultured cell monolayers, we have studied either endocrine cell phenotype differentiation markers or c-kit, a hematopoietic stem cell marker, has recently been involved with growth and differentiation  of <svg style="vertical-align:-2.29482pt;width:8.8500004px;" id="M1" height="13.425" version="1.1" viewBox="0 0 8.8500004 13.425" width="8.8500004"  xmlns="http://www.w3.org/2000/svg">
	<g transform="matrix(1.25,0,0,-1.25,0,13.425)">
		<g transform="translate(72,-61.26)">
			<text transform="matrix(1,0,0,-1,-71.95,63.6)">
				<tspan style="font-size: 12.50px; " x="0" y="0">𝛽</tspan>
			</text>

		</g>
	</g>
</svg>-cell subpopulations in human as well as rodent animal models. ESC which were found to either accelerate maturation and differentiation of the NPIs <svg style="vertical-align:-2.29482pt;width:8.8500004px;" id="M2" height="13.425" version="1.1" viewBox="0 0 8.8500004 13.425" width="8.8500004"  xmlns="http://www.w3.org/2000/svg">
	<g transform="matrix(1.25,0,0,-1.25,0,13.425)">
		<g transform="translate(72,-61.26)">
			<text transform="matrix(1,0,0,-1,-71.95,63.6)">
				<tspan style="font-size: 12.50px; " x="0" y="0">𝛽</tspan>
			</text>

		</g>
	</g>
</svg>-cell phenotype or identify an islet cell subpopulation that was marked positively for c-kit. The insulin/c-kit positive cells might represent a new, still unknown functionally immature <svg style="vertical-align:-2.29482pt;width:8.8500004px;" id="M3" height="13.425" version="1.1" viewBox="0 0 8.8500004 13.425" width="8.8500004"  xmlns="http://www.w3.org/2000/svg">
	<g transform="matrix(1.25,0,0,-1.25,0,13.425)">
		<g transform="translate(72,-61.26)">
			<text transform="matrix(1,0,0,-1,-71.95,63.6)">
				<tspan style="font-size: 12.50px; " x="0" y="0">𝛽</tspan>
			</text>

		</g>
	</g>
</svg>-cell like element in the porcine pancreas. Acceleration of maturation and differentiation of our NPI cell monolayers might generate a potential new opportunity to develop insulin-producing cells that may suite experimental trials for cell therapy of T1DM.

Francesca Mancuso

Mario Calvitti

Giovanni Luca

Claudio Nastruzzi

Tiziano Baroni

Stefania Mazzitelli

Ennio Becchetti

Iva Arato

Carlo Boselli

Monique D. Ngo Nselel

Riccardo Calafiore

Acceleration of Functional Maturation and Differentiation of Neonatal Porcine Islet Cell Monolayers Shortly In Vitro Cocultured with Microencapsulated Sertoli Cells

Leech embryogenesis is a model for investigating cellular and molecular processes of development. Due to the unusually large size of embryonic stem cells (teloblasts: 50–300 <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>μ</mml:mi></mml:math>m) in the glossiphoniid leech, <i>Theromyzon tessulatum</i>, and the presence of identifiable stem cell precursors (proteloblasts), we previously isolated a group of genes upregulated upon stem cell birth.  In the current study, we show that one of these genes, designated <i>Theromyzon</i> proliferation (<i>Tpr</i>), is required for normal stem cell genesis; specifically, transient <i>Tpr</i> knockdown experiments conducted with antisense oligonucleotides and monitored by semiquantitative RT-PCR, caused abnormal proteloblast proliferation leading to embryonic death, but did not overtly affect neuroectodermal or mesodermal stem cell development once these cells were born. <i>Tpr</i> encodes a large glutamine-rich (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mo>∼</mml:mo></mml:mrow></mml:math>34%) domain that shares compositional similarity with strong transcriptional enhancers many of which have been linked with trinucleotide repeat disorders (e.g., Huntington's).

Kristi A. Hohenstein

Shirley A. Lang

Tej Nuthulaganti

Daniel H. Shain

A Glutamine-Rich Factor Affects Stem Cell Genesis in Leech

Self-renewing Hematopoietic Stem Cells (HSCs) are responsible for reconstitution of all blood cell lineages. Sca-1 is the &#x201C;stem cell antigen&#x201D; marker used to identify  the primitive murine HSC population, the expression of which decreases upon differentiation to other mature cell types. <svg style="vertical-align:-0.17554pt;width:43.825001px;" id="M1" height="12.7875" version="1.1" viewBox="0 0 43.825001 12.7875" width="43.825001"  xmlns="http://www.w3.org/2000/svg">
	<g transform="matrix(1.25,0,0,-1.25,0,12.7875)">
		<g transform="translate(72,-61.77)">
			<text transform="matrix(1,0,0,-1,-71.95,61.99)">
				<tspan style="font-size: 12.50px; " x="0" y="0">S</tspan>
				<tspan style="font-size: 12.50px; " x="6.9516678" y="0">c</tspan>
				<tspan style="font-size: 12.50px; " x="12.503" y="0">a</tspan>
				<tspan style="font-size: 12.50px; " x="18.054333" y="0">-</tspan>
				<tspan style="font-size: 12.50px; " x="22.217831" y="0">1</tspan>
			</text>

			<text transform="matrix(1,0,0,-1,-43.48,67.16)">
				<tspan style="font-size: 8.75px; " x="0" y="0">+</tspan>
			</text>

		</g>
	</g>
</svg> HSCs maintain the bone marrow stem cell pool throughout the life. Aplastic anemia is a disease considered to involve primary stem cell deficiency and is characterized by severe pancytopenia and a decline in healthy blood cell generation system. Studies conducted in our laboratory revealed that the primitive <svg style="vertical-align:-0.17554pt;width:43.825001px;" id="M2" height="12.7875" version="1.1" viewBox="0 0 43.825001 12.7875" width="43.825001"  xmlns="http://www.w3.org/2000/svg">
	<g transform="matrix(1.25,0,0,-1.25,0,12.7875)">
		<g transform="translate(72,-61.77)">
			<text transform="matrix(1,0,0,-1,-71.95,61.99)">
				<tspan style="font-size: 12.50px; " x="0" y="0">S</tspan>
				<tspan style="font-size: 12.50px; " x="6.9516678" y="0">c</tspan>
				<tspan style="font-size: 12.50px; " x="12.503" y="0">a</tspan>
				<tspan style="font-size: 12.50px; " x="18.054333" y="0">-</tspan>
				<tspan style="font-size: 12.50px; " x="22.217831" y="0">1</tspan>
			</text>

			<text transform="matrix(1,0,0,-1,-43.48,67.16)">
				<tspan style="font-size: 8.75px; " x="0" y="0">+</tspan>
			</text>

		</g>
	</g>
</svg> BM-HSCs (bone marrow hematopoietic stem cell) are significantly affected in experimental Aplastic animals pretreated with chemotherapeutic drugs (Busulfan and Cyclophosphamide) and there is increased Caspase-3 activity with consecutive high Annexin-V positivity leading to premature apoptosis in the bone marrow hematopoietic stem cell population in Aplastic condition. The <svg style="vertical-align:-0.17554pt;width:62.674999px;" id="M3" height="14.275" version="1.1" viewBox="0 0 62.674999 14.275" width="62.674999"  xmlns="http://www.w3.org/2000/svg">
	<g transform="matrix(1.25,0,0,-1.25,0,14.275)">
		<g transform="translate(72,-60.58)">
			<text transform="matrix(1,0,0,-1,-71.95,60.8)">
				<tspan style="font-size: 12.50px; " x="0" y="0">S</tspan>
				<tspan style="font-size: 12.50px; " x="6.9516678" y="0">c</tspan>
				<tspan style="font-size: 12.50px; " x="12.503" y="0">a</tspan>
				<tspan style="font-size: 12.50px; " x="18.054333" y="0">-</tspan>
				<tspan style="font-size: 12.50px; " x="22.217831" y="0">1</tspan>
			</text>

			<text transform="matrix(1,0,0,-1,-43.48,65.97)">
				<tspan style="font-size: 8.75px; " x="0" y="0">b</tspan>
				<tspan style="font-size: 8.75px; " x="4.3759999" y="0">r</tspan>
				<tspan style="font-size: 8.75px; " x="7.4479518" y="0">i</tspan>
				<tspan style="font-size: 8.75px; " x="9.8810081" y="0">g</tspan>
				<tspan style="font-size: 8.75px; " x="14.257008" y="0">h</tspan>
				<tspan style="font-size: 8.75px; " x="18.633007" y="0">t</tspan>
			</text>

		</g>
	</g>
</svg>, that is, &#x201C;more primitive&#x201D; BM-HSC population was more affected than the &#x201C;less primitive&#x201D; BM-HSC <svg style="vertical-align:-0.17554pt;width:57px;" id="M4" height="14.275" version="1.1" viewBox="0 0 57 14.275" width="57"  xmlns="http://www.w3.org/2000/svg">
	<g transform="matrix(1.25,0,0,-1.25,0,14.275)">
		<g transform="translate(72,-60.58)">
			<text transform="matrix(1,0,0,-1,-71.95,60.8)">
				<tspan style="font-size: 12.50px; " x="0" y="0">S</tspan>
				<tspan style="font-size: 12.50px; " x="6.9516678" y="0">c</tspan>
				<tspan style="font-size: 12.50px; " x="12.503" y="0">a</tspan>
				<tspan style="font-size: 12.50px; " x="18.054333" y="0">-</tspan>
				<tspan style="font-size: 12.50px; " x="22.217831" y="0">1</tspan>
			</text>

			<text transform="matrix(1,0,0,-1,-43.48,65.97)">
				<tspan style="font-size: 8.75px; " x="0" y="0">d</tspan>
				<tspan style="font-size: 8.75px; " x="4.3759999" y="0">i</tspan>
				<tspan style="font-size: 8.75px; " x="6.8090558" y="0">m</tspan>
			</text>

		</g>
	</g>
</svg> population. The decreased cell population and the receptor expression were directly associated with an empty and deranged marrow microenvironment, which is evident from scanning electron microscopy (SEM). The above experimental evidences hint toward the manipulation of receptor expression for the benefit of cytotherapy by primitive stem cell population in Aplastic anemia cases.

Sumanta Chatterjee

Pratima Basak

Prosun Das

Madhurima Das

Jacintha Archana Pereira

Ranjan Kumar Dutta

Malay Chaklader

Samaresh Chaudhuri

Sujata Law

Primitive Sca-1 Positive Bone Marrow HSC in Mouse Model of Aplastic Anemia: A Comparative Study through Flowcytometric Analysis and Scanning Electron Microscopy

The characterization and isolation of various stem cell populations, from embryonic through tissue-derived stem cells, have led a rapid growth in the field of stem cell research. These research efforts have often been interrelated as to the markers that identify a select cell population are frequently analyzed to determine their expression in cells of distinct organs/tissues. In this review, we will expand the current state of research involving select tissue-derived stem cell populations including the liver, central nervous system, and cardiac tissues as examples of the success and challenges in this field of research. Lastly, the challenges of clinical therapies will be discussed as it applies to these unique
cell populations.

Leora J. Tesche

David A. Gerber

Tissue-Derived Stem and Progenitor Cells

The report describes the feasibility of the addition of multiple viable HLA-mismatched unrelated cord blood units, to a low cell number matched unrelated cord, to assist clinical engraftment. An ablative stem cell transplant was performed in an adult with relapsed acute lymphoblastic leukaemia (ALL), using a single HLA-matched cord blood unit (mononuclear cell dose <svg style="vertical-align:-0.3135pt;width:58.325001px;" id="M1" height="14.225" version="1.1" viewBox="0 0 58.325001 14.225" width="58.325001"  xmlns="http://www.w3.org/2000/svg">
	<g transform="matrix(1.25,0,0,-1.25,0,14.225)">
		<g transform="translate(72,-60.62)">
			<text transform="matrix(1,0,0,-1,-71.95,60.99)">
				<tspan style="font-size: 12.50px; " x="0" y="0">0</tspan>
				<tspan style="font-size: 12.50px; " x="6.2515001" y="0">.</tspan>
				<tspan style="font-size: 12.50px; " x="9.3772497" y="0">8</tspan>
				<tspan style="font-size: 12.50px; " x="18.404415" y="0">×</tspan>
				<tspan style="font-size: 12.50px; " x="29.182001" y="0">1</tspan>
				<tspan style="font-size: 12.50px; " x="35.433502" y="0">0</tspan>
			</text>

			<text transform="matrix(1,0,0,-1,-30.26,66.16)">
				<tspan style="font-size: 8.75px; " x="0" y="0">7</tspan>
			</text>

		</g>
	</g>
</svg>
), supported by six mismatched cord blood units (one unit per 10&#x2009;kg recipient weight). No adverse reaction occurred following the infusion of mismatched units and engraftment of the suboptimal-dose matched unit occurred rapidly, with no molecular evidence of engraftment of mismatched cords. Early molecular remission of ALL was demonstrated using a novel PCR for a mitochondrial DNA mutation in the leukaemic clone. The cell dose of the matched cord was well below that recommended to engraft a 70&#x2009;kg recipient. We suggest that a factor or factors in the mismatched cords enhanced/supported engraftment of the matched cord.

Stephen J. Proctor

Catherine E. Chapman

Rachel Sharples

Helen L. Lucraft

Jennifer Wilkinson

Jane Conn

Peter G. Middleton

Enhanced Engraftment of a Very Low-Dose Cord Blood Unit in an Adult Haemopoietic Transplant by Addition of Six Mismatched Viable Cord Units

About this journal

<p><em>Stem Cells International</em> publishes papers in all areas of stem cell biology and applications. The journal publishes basic, translational, and clinical research, including animal models and clinical trials.</p>


Journal profile

Meet the editorial board

<p>Chief Editor&nbsp;Professor Li&nbsp;has a background in cardiac stem cell transplantation, using young stem cells to promote tissue repair following injury to rejuvenate the aged individual, and the development of biomaterials that can easily integrate into damaged heart tissue.</p>


Editor spotlight

Submit to Special Issue

We currently have a number of Special Issues open for submission. Special Issues highlight emerging areas of research within a field, or provide a venue for a deeper investigation into an existing research area.

Special Issues

Author guidelines

Editorial board

Databases and indexing

Stem Cells International - Table of contents 2010

title

Stem Cells International publishes papers in all areas of stem cell biology and applications. The journal publishes basic, translational, and clinical research, including animal models and clinical trials.

Stem Cells International