Current Issue : January - March Volume : 2014 Issue Number : 1 Articles : 5 Articles
Introduction: Microspheres fabricated from natural materials serve as a promising biodegradable and\r\nbiocompatible carrier in a small volume for efficient cell delivery to the lesion of the injured neural tissue to\r\ngenerate biological functions. As the major component of extracellular matrix and due to its natural abundance\r\nwithin the body, collagen may be fabricated into microspheres and improve the ability of pre-seeded cells on the\r\nmicrospheres to encounter the hostile micro-environment in the lesion.\r\nMethods: In this study, collagen microspheres were fabricated using the water-in-oil emulsion technique and crosslinked\r\nwith 1-ethyl-3-(3-dimethylaminopropryl) carbodiimide. Oligodendrocyte progenitor cells isolated from\r\npostnatal day P1 to 2 rats were cultured and differentiated on the microspheres. The microspheres carrying the\r\noligodendrocyte progenitor cells were co-cultured with dorsal root ganglions from 15-day-old rat embryos. The\r\nmyelination formation was studied for the co-culture of oligodendrocyte progenitor cells and dorsal root ganglions.\r\nResults: We showed that the viability of oligodendrocyte progenitor cells, B104 cells and PC12 cells grown on\r\nmicrospheres was not significantly different with those in cell culture plates. Oligodendrocyte progenitor cells\r\ndifferentiated into oligodendrocytes on collagen microspheres. The oligodendrocytes grown on microspheres\r\nextended processes that wrapped the axons of dorsal root ganglion neurons and the formation of myelin sheath\r\nwas observed in the co-culture.\r\nConclusions: This study demonstrates the feasibility of collagen microspheres in further applications for the\r\ndelivery of neural progenitor cells for neural regeneration...
Introduction: Knowing the repertoire of cell signaling receptors would provide pivotal insight into the\r\ndevelopmental and regenerative capabilities of bone marrow cell (BMC)-derived hematopoietic stem/progenitor\r\ncells (HSPCs) and bone marrow mesenchymal stromal cells (BMMSCs).\r\nMethods: Murine HSPCs were enriched from fluorescence-activated cell sorting (FACS)-sorted Linââ?¬â??c-Kit+Sca-1+\r\nBMCs isolated from the tibia and femoral marrow compartments. Purified BMMSCs (CD73+, CD90+, CD105+, and\r\nCD45ââ?¬â??, CD34ââ?¬â??, CD31ââ?¬â??, c-Kitââ?¬â??) with extensive self-renewal potential and multilineage differentiation capacity\r\n(into different mesodermal cell lineages including osteocytes, chrondrocytes, adipocytes) were derived from\r\nadherent BMC cultures after CD45+ cell depletion. Adherent colony-forming cells were passaged two to three times\r\nand FACS analysis was used to assess cell purity and validate cell-specific surface marker phenotype prior to\r\nexperimentation. Gene transcripts for a number of cell signaling molecules were assessed using a custom\r\nquantitative real-time RT-PCR low-density microarray (94 genes; TaqManÃ?® technology).\r\nResults: We identified 16 mRNA transcripts that were specifically expressed in BMC-derived HSPC (including Ptprc,\r\nc-Kit, Csf3r, Csf2rb2, Ccr4, Cxcr3 and Tie-1), and 14 transcripts specifically expressed in BMMSCs (including Pdgfra,\r\nDdr2, Ngfr, Mst1r, Fgfr2, Epha3, and Ephb3). We also identified 27 transcripts that were specifically upregulated\r\n(=2-fold expression) in BMMSCs relative to HSPCs (Axl, Bmpr1a, Met, Pdgfrb, Fgfr1, Mertk, Cmkor1, Egfr, Epha7, and\r\nEphb4), and 19 transcripts that were specifically upregulated in HSPCs relative to BMMSCs (Ccr1, Csf1r, Csf2ra, Epor,\r\nIL6ra, and IL7r). Eleven transcripts were equally expressed (<2-fold upregulation) in HSPCs and BMMSCs (Flt1, Insr,\r\nKdr, Jak1, Agtrl1, Ccr3, Ednrb, Il3ra, Hoxb4, Tnfrsf1a, and Abcb1b), whilst another seven transcripts (Epha6, Epha8,\r\nMusk, Ntrk2, Ros1, Srms, and Tnk1) were not expressed in either cell population.\r\nConclusions: We demonstrate that besides their unique immunophenotype and functional differences, BMC-derived\r\nHSPCs and BMMSCs have different molecular receptor signaling transcript profiles linked to cell survival, growth, cell\r\ndifferentiation status, growth factor/cytokine production and genes involved in cell migration/trafficking/adhesion that\r\nmay be critical to maintain their pluripotency, plasticity, and stem cell function....
Introduction: Cell-based therapy represents a new frontier in the treatment of a wide variety of human diseases\r\ntraditionally associated with morbidity outcomes, including those involving inflammation, autoimmunity, tissue\r\ndamage, and cancer. However, the use of mesenchymal stem cells (MSCs) to treat multiple myeloma (MM) bone\r\ndisease has raised concerns. Specifically, evidence has shown that infused MSCs might support tumor growth and\r\nmetastasis.\r\nMethods: In this study, we used a standard disseminated MM model in mice to identify the in vivo effects of\r\nintravenous MSC infusion. In addition, a series of in vitro co-culture assays were preformed to explore whether\r\nFas/Fas ligand (Fas-L) is involved in the inhibitory effects of MSCs on MM cells.\r\nResults: In the MM mouse model, treatment of MSCs with highly expressed Fas ligand (Fas-Lhigh MSCs) showed\r\nremarkable inhibitory effects on MM indenization in terms of extending the mouse survival rate and inhibiting\r\ntumor growth, bone resorption in the lumbus and collum femoris, and MM cell metastasis in the lungs and kidneys.\r\nIn addition, reduced proliferation and increased apoptosis of MM cells was observed when co-cultured with\r\nFas-Lhigh MSCs in vitro. Furthermore, mechanistically, the binding between Fas and Fas-L significantly induced\r\napoptosis in MM cells, as evidenced through an increase in the expression of apoptosis marker and Fas in MM cells.\r\nIn contrast, Fas-Lnull MSCs promote MM growth.\r\nConclusions: These data suggest that Fas/Fas-L-induced MM apoptosis plays a crucial role in the MSC-based\r\ninhibition of MM growth. Although whether MSCs inhibit or promote cancer growth remains controversial, the\r\nlevels of Fas-L expression in MSCs determine, at least partially, the effects of MSCs on MM cell growth....
Introduction: Treatment of chronic skin wounds is difficult and largely ineffective. Little improvement has been\r\nshown in promoting the healing of these wounds in the past few decades. Innovative treatments to enhance\r\nchronic wound healing process are therefore needed.\r\nMethods: In this study, we examined the efficacy of angiopoietin-1 gene-modified bone marrow mesenchymal\r\nstem cells (Ang1-MSCs) on the promotion of cutaneous wound healing in rats. Excisional full-thickness wounds\r\nwere treated with Ang1-MSCs, a recombinant adenovirus encoding angiopoietin-1 (Ad-Ang1), unmodified bone\r\nmarrow mesenchymal stem cells (MSCs), or vehicle medium (sham).\r\nResults: The results showed that Ang1-MSCs significantly promoted wound healing with increased epidermal and\r\ndermal regeneration, and enhanced angiogenesis compared with MSCs, Ad-Ang1 or sham treatment. Moreover,\r\nAng1-MSCs expressed CD31 in the wound, suggesting a direct contribution of Ang1-MSCs to angiogenesis.\r\nConclusions: Here we show that Ang1-MSCs accelerate wound healing by promoting skin regeneration and\r\nangiogenesis, compared with MSCs or Ad-Ang1 alone....
Introduction: Potential stem cell niches (SNs) were recently reported in intervertebral discs (IVDs) and knee joints\r\n(KJs) in different mammals (located adjacent to the epiphyseal plate; EP). The aim here was to examine further\r\npossible cellular migration and migration directions of cells originating from niches possibly involved in\r\nregeneration of cartilaginous tissues in the IVD and in the KJ regions in adult mammals.\r\nMethods: In total, 33 rabbits were used in studies A through C.\r\nA. IVD cells were sorted; fluorescence-activated cell sorting (FACS) by size (forward scatter; =10 �µm or >10 �µm or\r\nGDF5 cells (anti-GDF5 antibody). Sorted cells, labeled with cell tracer (carboxyfluorescein-diacetatesuccinimidyl\r\nester; CDFA-SE) were applied on IVD explants in vitro. Migrating cells/distance was evaluated by\r\nfluorescence- and confocal-microscopy (FC).\r\nB. DNA labeling was performed with BrdU (oral administration). Animals were killed (14 to 56 days), KJs collected,\r\nand BrdU cells visualized with immunohistochemistry (IHC)/anti-BrdU antibody in SN and articular cartilage (AC).\r\nC. Cell tracer: (Fe-nanoparticles: Endorem) were injected into SNs of IVDs (LI-LV) and KJs (tibia). Animals were\r\nkilled after 2 to 6 weeks. Fe-labeled cells were traced by ferric-iron staining (Prussian blue reaction; Mallory\r\nmethod).\r\nResults: A. GDF5 cells and =10-�µm cells displayed the best migration capability in IVD explants. GDF5 cells were\r\ndetected at a tissue depth of 1,300 �µm (16 days). B. BrdU cells were observed in early time points in niches of KJs,\r\nand at later time points in AC, indicating a gradual migration of cells. C. Fe cells were detected in IVDs; in annulus\r\nfibrosus (AF) in 11 of 12 animals and in nucleus pulposus (NP) in two of 12 animals. In AC (tibia), Fe cells were\r\ndetected in six of 12 animals. In the potential migration route (PMR), from niches toward the IVD, Fe cells (three of\r\n12 animals) and in PMR toward AC (KJs) (six of 12 animals) were detected.\r\nConclusions: Results indicate similar cellular migration patterns in cartilage regions (IVD and KJs) with migration\r\nfrom stem cell niche areas into the mature cartilaginous tissues of both the KJs and the IVD. These findings of a\r\ncellular migration pattern in mature cartilage are of interest from tissue-repair and engineering perspectives....
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