Disease relevance of MSC

• The activated B-cell factor (ABF)-1 cDNA was initially isolated from Epstein-Barr virus (EBV)-infected B cells and codes for a DNA-binding protein belonging to the basic helix-loop-helix (bHLH) family of transcription factors [1].
• We injected primary MSC or saline into mice that lack the alpha3-chain of type IV collagen (COL4A3), a model of chronic kidney disease with close similarities to human Alport disease [2].
• Weekly injections of MSC from week 6 to 10 of life prevented the loss of peritubular capillaries and reduced markers of renal fibrosis, that is, interstitial volume, numbers of smooth muscle actin-positive interstitial cells, and interstitial collagen deposits as compared to saline-injected COL4A3-deficient mice [2].
• However, renal function, that is, blood urea nitrogen, creatinine levels, proteinuria as well as survival of COL4A3-deficient mice were not affected by MSC injections [2].
• RESULTS: Human MSC showed an extensive invasion into glioma spheroids [3].

High impact information on MSC

• These findings provide a molecular model of how LTA expression may be genetically regulated by allele-specific recruitment of the transcriptional repressor ABF-1 [4].
• We found that activated B-cell factor-1 (ABF-1) binds to this site in vitro and suppresses reporter gene expression, but only in the presence of the LTA+80A allele [4].
• Intrinsic inhibition of transcription factor E2A by HLH proteins ABF-1 and Id2 mediates reprogramming of neoplastic B cells in Hodgkin lymphoma [5].
• The B cell-specific transcription factor program was disrupted by overexpression of the helix-loop-helix proteins ABF-1 and Id2 [5].
• In the hMSC-treated diabetic mice, there was an increase in pancreatic islets and beta cells producing mouse insulin [6].

Chemical compound and disease context of MSC

• A senna and docusate sodium preparation (Senokot-S Tablets; SKS) was used to alleviate opioid-induced constipation; consequently there was a significantly lower (p = 0.02) incidence of constipation during treatment with MSC [7].
• HMSC were cultured under physiologically relevant oxygen environments (2% O2) in three-dimensional (3D) constructs for up to 1 month in order to investigate the combined effects of chronic hypoxia and 3D architecture on hMSC tissue-development patterns [8].

Biological context of MSC

• ABF-1 contains a transcriptional repression domain and is capable of inhibiting the transactivation capability of E47 in mammalian cells [9].
• Using a yeast two-hybrid screen, we have identified a new bHLH transcription factor, ABF-1, from a human B-cell cDNA library [9].
• Transient transfection of ABF-1 deletion mutants demonstrated that the N-terminal amino acids 1 to 40 and the bHLH domain function together to achieve maximum repression of E2A activity [1].
• Taken together, these results indicate that ABF-1 is a nuclear transcriptional repressor with two distinct regions that function in a synergistic fashion to attenuate E2A-mediated gene activation [1].
• The aim of this study was to define pelvic floor function in patients with multiple sclerosis and bowel dysfunction, either incontinence (MSI) or defecation difficulties without incontinence (MSC) [10].

Anatomical context of MSC

• BACKGROUND: Whether aging modifies mesenchymal stem cell (MSC) properties is unknown [11].
• Characterization of ABF-1, a novel basic helix-loop-helix transcription factor expressed in activated B lymphocytes [9].
• Furthermore, a heterodimeric complex containing ABF-1 and E2A can be detected in EBV-immortalized lymphoblastoid cell lines [9].
• OBJECTIVES: To determine the biological characteristics of human embryonic MSC (hMSC) and their potential for differentiation into epithelial cells [12].
• Multipotent mesenchymal stem or stromal cells (MSC) have shown to improve outcome of acute renal injury models, but whether MSC can delay renal failure in chronic kidney disease is not known [2].

Associations of MSC with chemical compounds

• MSC were transduced using retroviral vectors encoding the neomycin resistance gene (Neo(R)) and a second gene encoding either the human soluble tumor necrosis factor receptor (hsTNFRII) or beta-galactosidase (beta-Gal) [13].
• The aim of this study was to investigate the effects of 17beta-estradiol (E2) and testosterone in human-bone-marrow-derived mesenchymal stem cell (MSC) cultures from both female and male donors of various ages [14].
• Interferon-gamma, in combination with interleukin-1beta or lipopolysaccharide, evoked a transient (4 h < time < 24 h) iNOS mRNA expression in human MSC and preadipocyte-derived adipocytes, respectively [15].
• The aim of this study was to use silane-modified surfaces to control MSC adhesion and differentiation in vitro and evaluate the use of such techniques to control MSC behaviour both in basal and stimulated conditions [16].
• In this study, we examined whether modifying highly adsorbent materials like hydroxyapatite (HA) with RGD peptides would improve mesenchymal stem cell (MSC) adhesion [17].

Regulatory relationships of MSC

• A recent study by Dörken and colleagues provides an interesting insight into the mechanisms for this reprogramming by demonstrating that the key B-cell-determining transcription factor E2A is inhibited in HRS cells by the deregulated expression of its inhibitors activated B-cell factor (ABF)-1 and inhibitor of differentiation and DNA binding (Id)2 [18].
• Type I interferon (IFN) is shown to control the reversible quiescence of a primitive human bone marrow mesenchymal stem cell (MSC) subpopulation [19].

Other interactions of MSC

• After stimulation and in vivo transplantation, hMSC possess the potential to differentiate into epidermal cells with the production of keratin 19 and E-cadherin [12].
• Characterization of a basic helix-loop-helix protein, ABF-1: nuclear localization, transcriptional properties, and interaction with Id-2 [1].
• To study tissue-specific homing, murine CD34- MSC lines showing concordant chemokine receptor expression were either transiently labeled with CMFDA, or were stably transfected with green fluorescent protein (GFP) expression plasmids [20].
• A range of characterised clean glass silane-modified surfaces, methyl (-CH(3)), amino (-NH(2)), silane (-SH), hydroxyl (-OH) and carboxyl (-COOH), were produced and cultured in contact with human MSC, in conjunction with a clean glass (TAAB) control, for time periods up to 28 days in basal, chondrogenic and osteogenic stimulated media [16].
• Overexpression of MCP-3 1 month after MI restored MSC homing to the heart [21].

Analytical, diagnostic and therapeutic context of MSC

• Using haplotype-specific chromatin immunoprecipitation, we confirmed that ABF-1 is preferentially recruited to the low-producer allele in vivo [4].
• Our results indicate that precursor cells characteristic of a MSC population can be cultured from differentiating hESCs through embryoid bodies, thus holding great promise for a potentially unlimited source of cells for cartilage tissue engineering [22].
• The biological characteristics of hMSC were detected by immunohistochemical methods and flow cytometry [12].
• Myoblasts in contact coculture with MNC or MSC showed no synergistic effect [23].
• We prospectively and randomly allocated 30 patients with cerebral infarcts within the middle cerebral arterial territory and with severe neurological deficits into one of two treatment groups: the MSC group (n = 5) received intravenous infusion of 1 x 10(8) autologous MSCs, whereas the control group (n = 25) did not receive MSCs [24].

References