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CD146 expression on primary nonhematopoietic bone marrow stem cells is correlated with in situ localization.

ABSTRACT: Nonhematopoietic bone marrow mesenchymal stem cells (BM-MSCs) are of central importance for bone marrow stroma and the hematopoietic environment. However, the exact phenotype and anatomical distribution of specified MSC populations in the marrow are unknown. We characterized the phenotype of primary human BM-MSCs and found that all assayable colony-forming units-fibroblast (CFU-Fs) were highly and exclusively enriched not only in the lin?/CD271?/CD45?/CD146? stem-cell fraction, but also in lin?/CD271?/CD45?/CD146(?/low) cells. Both populations, regardless of CD146 expression, shared a similar phenotype and genotype, gave rise to typical cultured stromal cells, and formed bone and hematopoietic stroma in vivo. Interestingly, CD146 was up-regulated in normoxia and down-regulated in hypoxia. This was correlated with in situ localization differences, with CD146 coexpressing reticular cells located in perivascular regions, whereas bone-lining MSCs expressed CD271 alone. In both regions, CD34? hematopoietic stem/progenitor cells were located in close proximity to MSCs. These novel findings show that the expression of CD146 differentiates between perivascular versus endosteal localization of non-hematopoietic BM-MSC populations, which may be useful for the study of the hematopoietic environment.

SUBMITTER: Tormin A

PROVIDER: S-EPMC3109533 | biostudies-other | 2011 May

REPOSITORIES: biostudies-other

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CD146 expression on primary nonhematopoietic bone marrow stem cells is correlated with in situ localization.

Tormin Ariane A Li Ou O Brune Jan Claas JC Walsh Stuart S Schütz Birgit B Ehinger Mats M Ditzel Nicholas N Kassem Moustapha M Scheding Stefan S

Blood 20110317 19

Nonhematopoietic bone marrow mesenchymal stem cells (BM-MSCs) are of central importance for bone marrow stroma and the hematopoietic environment. However, the exact phenotype and anatomical distribution of specified MSC populations in the marrow are unknown. We characterized the phenotype of primary human BM-MSCs and found that all assayable colony-forming units-fibroblast (CFU-Fs) were highly and exclusively enriched not only in the lin⁻/CD271⁺/CD45⁻/CD146⁺ stem-cell fraction, but also in lin⁻/ ...[more]

PMID: 21415267

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Project description:IntroductionPremature ovarian insufficiency (POI) is a challenging issue in terms of reproduction biology. In this study, therapeutic properties of bone marrow CD146+ mesenchymal stem cells (MSCs) and CD144+ endothelial cells (ECs) were separately investigated in rats with POI.MethodsPOI rats were classified into control POI, POI + CD146+ MSCs, and POI + CD144+ ECs groups. Enriched CD146+ MSCs and CD144+ ECs were directly injected into ovarian tissue (15 × 104 cells/10 μL) in relevant groups. After 4 weeks, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) levels were measured in blood samples. Ovarian tissues were collected and subjected to Hematoxylin-Eosin and Masson's trichrome staining. The expression of angp-2, vegfr-2, smad-2, -4, -6, and tgf-β1 was studied using qRT-PCR analysis. Histopathological examination indicated an increased pattern of atretic follicles in the POI group related to the control rats (P<0.0001).ResultsData indicated that injection of POI + CD146+ MSCs and CD144+ ECs in POI rats reduced atretic follicles and increased the number of normal follicles (P<0.01). Along with these changes, the content of blue-colored collagen fibers was diminished after cell transplantation. Besides, cell transplantation in POI rats had the potential to reduce increased FSH, and LH levels (P<0.05). In contrast, E2 content was increased in POI + CD146+ MSCs and POI + CD144+ ECs groups compared to control POI rats, indicating restoration of follicular function. CD144+ (smad-2, and -4) and CD146+ (smad-6) cells altered the activity of genes belonging TGF-β signaling pathway. Unlike POI + CD146+ MSCs, aberrant angiogenesis properties were significantly down-regulated in POI + CD144+ ECs related to the control POI group (P<0.05).ConclusionThe transplantation of bone marrow CD146+ and CD144+ cells can lead to the restoration of ovarian tissue function in POI rats via modulating different mechanisms associated with angiogenesis and fibrosis.

Project description:BACKGROUND: The human cysteine rich protein 61 (CYR61, CCN1) as well as the other members of the CCN family of genes play important roles in cellular processes such as proliferation, adhesion, migration and survival. These cellular events are of special importance within the complex cellular interactions ongoing in bone remodeling. Previously, we analyzed the role of CYR61/CCN1 as an extracellular signaling molecule in human osteoblasts. Since mesenchymal stem cells of bone marrow are important progenitors for various differentiation pathways in bone and possess increasing potential for regenerative medicine, here we aimed to analyze the expression of CCN family members in bone marrow-derived human mesenchymal stem cells and along the osteogenic, the adipogenic and the chondrogenic differentiation. RESULTS: Primary cultures of human mesenchymal stem cells were obtained from the femoral head of patients undergoing total hip arthroplasty. Differentiation into adipocytes and osteoblasts was done in monolayer culture, differentiation into chondrocytes was induced in high density cell pellet cultures. For either pathway, established differentiation markers and CCN-members were analyzed at the mRNA level by RT-PCR and the CYR61/CCN1 protein was analyzed by immunocytochemistry.RT-PCR and histochemical analysis revealed the appropriate phenotype of differentiated cells (Alizarin-red S, Oil Red O, Alcian blue, alkaline phosphatase; osteocalcin, collagen types I, II, IX, X, cbfa1, PPARgamma, aggrecan). Mesenchymal stem cells expressed CYR61/CCN1, CTGF/CCN2, CTGF-L/WISP2/CCN5 and WISP3/CCN6. The CYR61/CCN1 expression decreased markedly during osteogenic differentiation, adipogenic differentiation and chondrogenic differentiation. These results were confirmed by immuncytochemical analyses. WISP2/CCN5 RNA expression declined during adipogenic differentiation and WISP3/CCN6 RNA expression was markedly reduced in chondrogenic differentiation. CONCLUSION: The decrease in CYR61/CCN1 expression during the differentiation pathways of mesenchymal stem cells into osteoblasts, adipocytes and chondrocytes suggests a specific role of CYR61/CCN1 for maintenance of the stem cell phenotype. The differential expression of CTGF/CCN2, WISP2/CCN5, WISP3/CCN6 and mainly CYR61/CCN1 indicates, that these members of the CCN-family might be important regulators for bone marrow-derived mesenchymal stem cells in the regulation of proliferation and initiation of specific differentiation pathways.

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CD146 expression on primary nonhematopoietic bone marrow stem cells is correlated with in situ localization.

Publications

CD146 expression on primary nonhematopoietic bone marrow stem cells is correlated with in situ localization.

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