scholarly journals Cell Therapy of Pathological Gastrointestinal Lesions in Modeled NSAID-Induced Enterocolitis

Biomeditsina ◽  
2021 ◽  
Vol 17 (3) ◽  
pp. 48-55
Author(s):  
R. A. Klesov ◽  
O. I. Stepanova ◽  
V. N. Karkischenko ◽  
O. V. Baranova
Keyword(s):  
Stromal Cells ◽  
Wistar Rats ◽  
Mononuclear Cells ◽  
Bone Marrow Cells ◽  
Multipotent Mesenchymal Stromal Cells ◽  
Simultaneous Administration ◽  
Inflammatory Phase ◽  
Gastrointestinal Lesions ◽  
Regenerative Phase

Wistar rats with NSAID-induced (dexketoprofen) chronic enterocolitis of the gastrointestinal tract were treated with a cultured allogeneic cell suspension consisting of mononuclear cells (40 millions) and multipotent mesenchymal stromal cells (10 millions). The suspension was transplanted intraperitoneally, 2 times with an interval of 30 days. Cultured allogeneic fractions of bone marrow cells accelerate the regeneration of long-term non-healing gastrointestinal lesions by reducing the duration and severity of the inflammatory phase and activating the regenerative phase of the ulcerative process. It was found that the simultaneous administration of the studied cultured stem cells can be used for the treatment of chronic, long-term non-healing, poorly-scarring ulcerative necrotic gastrointestinal pathologies.

scholarly journals Bisecting GlcNAc structure is implicated in suppression of stroma-dependent haemopoiesis in transgenic mice expressing N-acetylglucosaminyltransferase III

1998 ◽  
Vol 331 (3) ◽  
pp. 733-742 ◽  
Author(s):  
Masafumi YOSHIMURA ◽  
Yoshito IHARA ◽  
Tetsuo NISHIURA ◽  
Yu OKAJIMA ◽  
Megumu OGAWA ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Transgenic Mice ◽  
Stromal Cells ◽  
Bone Marrow Cells ◽  
Adherent Cell ◽  
Wild Type ◽  
Spleen Cells ◽  
Bisecting Glcnac ◽  
Marrow Cells

Several sugar structures have been reported to be necessary for haemopoiesis. We analysed the haematological phenotypes of transgenic mice expressing β-1,4 N-acetylglucosaminyltransferase III (GnT-III), which forms bisecting N-acetylglucosamine on asparagine-linked oligosaccharides. In the transgenic mice, the GnT-III activity was elevated in bone marrow, spleen and peripheral blood and in isolated mononuclear cells from these tissues, whereas no activity was found in these tissues of wild-type mice. Stromal cells after long-term cultures of transgenic-derived bone marrow and spleen cells also showed elevated GnT-III activity, compared with an undetectable activity in wild-type stromal cells. As judged by HPLC analysis, lectin blotting and lectin cytotoxicity assay, bisecting GlcNAc residues were increased on both blood cells and stromal cells from bone marrow and spleen in transgenic mice. The transgenic mice displayed spleen atrophy, hypocellular bone marrow and pancytopenia. Bone marrow cells and spleen cells from transgenic mice produced fewer haemopoietic colonies. After lethal irradiation followed by bone marrow transplantation, transgenic recipient mice showed pancytopenia compared with wild-type recipient mice. Bone marrow cells from transgenic donors gave haematological reconstitution at the same level as wild-type donor cells. In addition, non-adherent cell production was decreased in long-term bone marrow cell cultures of transgenic mice. Collectively these results indicate that the stroma-supported haemopoiesis is compromised in transgenic mice expressing GnT-III, providing the first demonstration that the N-glycans have some significant roles in stroma-dependent haemopoiesis.

scholarly journals Long-term Engraftment of Multipotent Mesenchymal Stromal Cells That Differentiate to Form Myogenic Cells in Dogs With Duchenne Muscular Dystrophy

2012 ◽  
Vol 20 (1) ◽  
pp. 168-177 ◽  
Author(s):  
Yuko Nitahara-Kasahara ◽  
Hiromi Hayashita-Kinoh ◽  
Sachiko Ohshima-Hosoyama ◽  
Hironori Okada ◽  
Michiko Wada-Maeda ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Multipotent Mesenchymal Stromal Cells ◽  
Myogenic Cells

scholarly journals Studies in feline long-term marrow culture: hematopoiesis on normal and feline leukemia virus infected stromal cells

Blood ◽  
1992 ◽  
Vol 80 (3) ◽  
pp. 651-662
Author(s):  
ML Linenberger ◽  
JL Abkowitz
Keyword(s):  
Stromal Cells ◽  
Mononuclear Cells ◽  
Clonal Selection ◽  
Leukemia Virus ◽  
Feline Leukemia Virus ◽  
Erythroid Progenitors ◽  
Gag Protein ◽  
Cell Engraftment

To study the effects of feline leukemia virus (FeLV) on the hematopoietic microenvironment, a two-step feline long-term marrow culture (LTMC) system was developed and characterized. The adherent, stromal layer of these cultures is composed of fibroblastoid cells (50% to 80%), macrophages (10% to 30%), fat cells (10% to 20%), and large, polygonal cells that express muscle actin (1% to 2%). When fresh, enriched marrow mononuclear cells (MMNC) were added to 3-week-old irradiated stromal cultures, nonadherent erythroid progenitors (BFU-E) and granulocyte/macrophage progenitors (CFU-GM) could be detected for up to 5 and 12 weeks, respectively. LTMC stromal layers established from marrow cells from cats viremic with either a nonpathogenic strain of FeLV (FeLV-A/61E) or the anemogenic strain FeLV-C/Sarma were morphologically equivalent to uninfected LTMC stromal layers, although more than 80% of the stromal cells expressed FeLV gag protein. When FeLV-infected stromal cultures were recharged with uninfected MMNC, altered patterns of hematopoiesis were observed, compared with recharged, uninfected stromal cultures. In cultures with infected stroma, fewer nonadherent cells (NAC), nonadherent BFU-E, and nonadherent CFU-GM were detected during the first 4 to 5 weeks after recharge. In contrast, greater numbers of NAC and nonadherent CFU-GM were found from weeks 5 to 12 after recharge. When FeLV-infected stromal cultures were recharged with MMNC from a cat heterozygous for the X-chromosome-linked enzyme glucose-6-phosphate dehydrogenase (G-6- PD), the percentage of nonadherent CFU-GM expressing the domestic type G-6-PD isoenzyme remained stable over time (mean % domestic [%d], 53% +/- 3%), and was equivalent to that of nonadherent CFU-GM maintained in uninfected cultures (mean %d, 56% +/- 3%), indicating that clonal drift or clonal selection was not responsible for the enhanced maintenance of CFU-GM. Furthermore, as only 10% to 20% of recharged hematopoietic cells became infected with FeLV in vitro, it is unlikely that the altered pattern was due to progenitor infection. We hypothesize that the increase in NAC and nonadherent CFU-GM in FeLV-infected cultures resulted from enhanced growth factor production by stromal cells. The two-step LTMC system may facilitate the characterization of stromal- derived factors that affect progenitor cell engraftment and proliferation.

Expression of the G-CSF receptor on hematopoietic progenitor cells is not required for their mobilization by G-CSF

Blood ◽  
2000 ◽  
Vol 95 (10) ◽  
pp. 3025-3031 ◽  
Author(s):  
Fulu Liu ◽  
Jennifer Poursine-Laurent ◽  
Daniel C. Link
Keyword(s):  
Bone Marrow ◽  
Stromal Cells ◽  
Bone Marrow Cells ◽  
Hematopoietic Cells ◽  
Cell Types ◽  
Hematopoietic Progenitor Cell ◽  
Hematopoietic Progenitor ◽  
Definitive Evidence ◽  
In Trans

Abstract The mechanisms that regulate hematopoietic progenitor cell (HPC) mobilization from the bone marrow to blood have not yet been defined. HPC mobilization by granulocyte colony-stimulating factor (G-CSF), cyclophosphamide (CY), or interleukin-8 but not flt-3 ligand is markedly impaired in G-CSF receptor–deficient (G-CSFR–deficient) mice. G-CSFR is expressed on mature hematopoietic cells, HPCs, and stromal cells, which suggests that G-CSFR signals in one or more of these cell types was required for mobilization by these agents. To define the cell type(s) responsible for G-CSF–dependent mobilization, a series of chimeric mice were generated using bone marrow transplantation. Mobilization studies in these chimeras demonstrated that expression of the G-CSFR on transplantable hematopoietic cells but not stromal cells is required for CY- or G-CSF–induced mobilization. Moreover, in irradiated mice reconstituted with both wild type and G-CSFR–deficient bone marrow cells, treatment with CY or G-CSF resulted in the equal mobilization of both types of HPCs. This result held true for a broad spectrum of HPCs including colony-forming cells, CD34+lineage− and Sca+ lineage−cells, and long-term culture initiating cells. Collectively, these data provide the first definitive evidence that expression of the G-CSFR on HPCs is not required for their mobilization by G-CSF and suggest a model in which G-CSFR–dependent signals act in trans to mobilize HPCs from the bone marrow.

scholarly journals Persistence of Human Parvovirus B19 in Multipotent Mesenchymal Stromal Cells Expressing the Erythrocyte P antigen: Implications for Transplantation

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4745-4745
Author(s):  
Mikael Sundin ◽  
Anna Lindblom ◽  
Claes Örvell ◽  
A. John Barrett ◽  
Berit Sundberg ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Bone Marrow Cells ◽  
Parvovirus B19 ◽  
Multipotent Mesenchymal Stromal Cells ◽  
Erythema Infectiosum ◽  
Hematopoietic Stem ◽  
Healthy Donors ◽  
Severe Pancytopenia

Abstract Multipotent mesenchymal stromal cells (MSC) are used to improve the outcome of hematopoietic stem cell transplantation (HSCT) and in regenerative medicine. However, human MSC may harbor persistent viruses that may compromise their clinical benefit. Parvovirus B19, known to cause the childhood disease erythema infectiosum (“fifth disease”), can be hazardous to HSCT recipients due to development of a virus mediated severe pancytopenia. Retro spectively screened, 1 of 20 MSC from healthy donors contained B19 DNA. The donors exhibited a seroprevalence of anti-B19 IgG comparable to the reported normal level. Using flow cytometry, we found that human MSC (n=6) expressed the erythrocyte P antigen (also called globoside), reported as the B19 receptor, and Ku 80, a reported B19 co-receptor. After in vitro exposure to plasma derived from B19 viremic patients, MSC (n=3) were found positive for intracellular B19 proteins as determined by immunofluorescence. This demonstrates that MSC can be infected by B19. Further studies revealed that MSC could transmit B19 to bone marrow cells in vitro, suggesting that the virus can persist in the marrow stroma of healthy individuals. Two HSCT patients received the B19 positive MSC as treatment for graft-versus-host disease. Neither developed viremia nor symptomatic B19 infection, even though they where severely immunocompromised by means of subnormal Ig levels, low leukocyte counts and poor responses in mixed lymphocyte cultures. These results demonstrate for the first time that persistent B19 in MSC can infect hematopoietic cells and underscore the importance of monitoring B19 transmission by MSC products.

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