A subset of human rapidly self-renewing marrow stromal cells preferentially engraft in mice

Lee, Ryang Hwa; Hsu, Shih-Hsin; Munoz, James R.; Jung, Jin Sup; Lee, Na Rea; Pochampally, Radhika; Prockop, Darwin J.

doi:10.1182/blood-2005-07-2701

Cited by 112 publications

(81 citation statements)

References 51 publications

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“…44,45 Sites in which active neurogenesis occurs in adulthood, such as the hippocampus, subventricular zone and olfactory bulb, are often included in these preferred engraftment sites. 6,[46][47][48] In this respect the results of this study are not surprising. However, the non-proportional engraftment of MSCs in the hippocampus and dentate gyrus suggests a possible preference to these sites in 'depressed' FSL rats.…”

Section: Discussionsupporting

confidence: 64%

“…However, the non-proportional engraftment of MSCs in the hippocampus and dentate gyrus suggests a possible preference to these sites in 'depressed' FSL rats. As most studies relate MSC migration and engraftment with the expression of chemokine receptors and adhesion molecules, 45,47 it would be interesting to test their role in the engraftment of MSCs in 'depressed' FSL rats in the future.…”

Section: Discussionmentioning

confidence: 99%

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Mesenchymal stem cells increase hippocampal neurogenesis and counteract depressive-like behavior

et al. 2009

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Adult bone marrow-derived mesenchymal stem cells (MSCs) are regarded as potential candidates for treatment of neurodegenerative disorders, because of their ability to promote neurogenesis. MSCs promote neurogenesis by differentiating into neural lineages as well as by expressing neurotrophic factors that enhance the survival and differentiation of neural progenitor cells. Depression has been associated with impaired neurogenesis in the hippocampus and dentate gyrus. Therefore, the aim of this study was to analyze the therapeutic potential of MSCs in the Flinders sensitive line (FSL), a rat animal model for depression. Rats received an intracerebroventricular injection of culture-expanded and 1,1 0 -dioctadecyl-3,3,3 0 ,3 0 -tetramethylindocarbocyanine perchlorate (DiI)-labeled bone marrow-derived MSCs (10 5 cells). MSC-transplanted FSL rats showed significant improvement in their behavioral performance, as measured by the forced swim test and the dominant-submissive relationship (DSR) paradigm. After transplantation, MSCs migrated mainly to the ipsilateral dentate gyrus, CA1 and CA3 regions of the hippocampus, and to a lesser extent to the thalamus, hypothalamus, cortex and contralateral hippocampus. Neurogenesis was increased in the ipsilateral dentate gyrus and hippocampus of engrafted rats (granular cell layer) and was correlated with MSC engraftment and behavioral performance. We therefore postulate that MSCs may serve as a novel modality for treating depressive disorders.

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Section: Discussionsupporting

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Mesenchymal stem cells increase hippocampal neurogenesis and counteract depressive-like behavior

et al. 2009

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“…A limitation in our study is that our cells are cultivated and their behavior may differ from endogenous BM-MSCs. Notably, a recent study shows that a small subpopulation of bone marrow-adherent cells that are small in size, seen in the colonies of the earliest passages, express high levels of CXCR4, exhibit greater engraftment after systemic infusion (Lee et al, 2006). However, these small cells depend on the larger cells for survival and diminish quickly with successive passages, and they almost disappear in passage 3 (Colter et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

“…␤-Actin gene was used as an internal control to normalized equal loading of DNA per reaction. Assuming each MSC contains one copy of Y chromosome and 5 pg of DNA per diploid nucleus, the numbers of BM-MSCs in the myocardium below the ligation were determined (Lee et al, 2006). …”

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confidence: 99%

Mesenchymal Stem Cells Use Integrin β1 Not CXC Chemokine Receptor 4 for Myocardial Migration and Engraftment

Huang

et al. 2007

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Recent evidence has demonstrated the importance of bone marrow-derived mesenchymal stem cells (BM-MSCs) in the repair of damaged myocardium. The molecular mechanisms of engraftment and migration of BM-MSCs in the ischemic myocardium are unknown. In this study, we developed a functional genomics approach toward the identification of mediators of engraftment and migration of BM-MSCs within the ischemic myocardium. Our strategy involves microarray profiling (>22,000 probes) of ischemic hearts, complemented by reverse transcription-polymerase chain reaction and fluorescence-activated cell sorting of corresponding adhesion molecule and cytokine receptors in BM-MSCs to focus on the coexpressed pairs only. Our data revealed nine complementary adhesion molecules and cytokine receptors, including integrin ␤1, integrin ␣4, and CXC chemokine receptor 4 (CXCR4). To examine their functional contributions, we first blocked selectively these receptors by preincubation of BM-MSCs with specific neutralizing antibodies, and then we administered these cells intramyocardially. A significant reduction in the total number of BM-MSC in the infarcted myocardium was observed after integrin ␤1 blockade but not integrin ␣4 or CXCR4 blockade. The latter observation is distinctively different from that reported for hematopoietic stem cells (HSCs). Thus, our data show that BM-MSCs use a different pathway from HSCs for intramyocardial trafficking and engraftment. INTRODUCTIONCardiac repair and remodeling after ischemic injury involves myocyte hypertrophy, collagen deposition, and possibly ventricular dilatation (Sutton and Sharpe, 2000). Recent provocative data suggest that stem cells, either resident in the heart or originating from the bone marrow, may play an important role in the repair and regeneration of the injured myocardium (Anversa and Nadal-Ginard, 2002). We and others have shown that intramyocardial transplantation of bone marrow-derived stem cells (BMSCs) can promote cardiac repair with resulting functional improvement and reduced infarct size (Kocher et al., 2001;Mangi et al., 2003;Amado et al., 2005). In addition to direct transplantation, mobilization of BMSCs with cytokines such as granulocytecolony stimulating factor (G-CSF) and stem cell factor has been reported to enhance myocardial repair and improve cardiac function (Anversa and Nadal-Ginard, 2002;Askari et al., 2003). However, in a recent trial, the subcutaneous administration of G-CSF after acute myocardial infarction (MI) did not lead to further improvement in ventricular function compared with conventional treatment (Ripa et al., 2006). These controversial findings suggest the need to understand the molecular mechanisms involved with stem cell migration and engraftment into the infarcted myocardium.It has been reported that hematopoietic stem cells (HSCs) migrate in response to stromal-derived factor (SDF)-1␣, the ligand for the CXC chemokine receptor 4 (CXCR4) (Wright et al., 2002), and the up-regulation of SDF-1 in the ischemic myocardium mediates homing of HSCs vi...

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“…MSC can also produce a variety of growth factors, cytokines, chemokines and proteases that are likely to play a role either in their immunomodulatory or in their migratory function [29][30][31]. In this respect, MSC have been shown to express a restricted pattern of chemokine receptors, including CXCR4, allowing them to migrate to tissues upon specific chemotactic triggers [32][33][34][35]. These features are likely to represent the basis for MSC homing to multiple organs where they undergo a program of tissue-specific differentiation [36].…”

Section: Immunological Phenotype and Functions Of Mscmentioning

confidence: 99%

Immunoregulatory function of mesenchymal stem cells

2006

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Mesenchymal stem cells (MSC) are a rare subset of stem cells residing in the bone marrow where they closely interact with hematopoietic stem cells and support their growth and differentiation. MSC can differentiate into multiple mesenchymal and non‐mesenchymal lineages, providing a promising tool for tissue repair. In addition, MSC suppress many T cell, B cell and NK cell functions and may affect also dendritic cell activities. Due to their limited immunogenicity, MSC are poorly recognized by HLA‐incompatible hosts. Based on these unique properties, MSC are currently under investigation for their possible use to treat immuno‐mediated diseases. However, both their condition of immunoprivilege and their immunosuppressive function have recently been challenged when analyzed under particular experimental conditions. Thus, it is likely that MSC effects on the immune system may be deeply influenced not only by cell‐to‐cell interactions, but also by environmental factors shaping their phenotype and functions.

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A subset of human rapidly self-renewing marrow stromal cells preferentially engraft in mice

Cited by 112 publications

References 51 publications

Mesenchymal stem cells increase hippocampal neurogenesis and counteract depressive-like behavior

Mesenchymal stem cells increase hippocampal neurogenesis and counteract depressive-like behavior

Mesenchymal Stem Cells Use Integrin β1 Not CXC Chemokine Receptor 4 for Myocardial Migration and Engraftment

Immunoregulatory function of mesenchymal stem cells

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