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Biomedical subjects

Nagwa S El-Badri

Publications and source records attributed to Nagwa S El-Badri.

8 recordsLinked to original sources
PubMed2006

Cord blood mesenchymal stem cells: Potential use in neurological disorders.

Our previous studies demonstrate enhanced neural protective effects of cord blood (CB) cells in comparison to stem cells from adult marrow. To determine further whether mesenchymal stem cells (MSCs) derived from human umbilical cord blood (hUCB) possess optimal characteristics for neural therapy, we isolated populations of plastic-adherent CB MSCs. These cells generated CD34-, CD45-, CD11b-, CD3-, CD19- cells in culture and failed to produce CFU-M, CFU-GEMM, or CFU-GM hematopoietic colonies in methylcellulose. However, cultured CB MSCs possessed a remarkable ability to support proliferation as well as differentiation of hematopoietic cells in vitro. In addition, supernatants from cultured CB MSCs promoted survival of NT2 N neural cells and peripheral blood mononuclear cells (MNCs) cultured under conditions designed to induce cell stress and limit protein synthesis. After incubation in neural differentiation medium, CB MSCs expressed the neural cell-surface antigen A2B5, the neurofilament polypeptide NF200, the oligodendrocyte precursor marker 04, intermediate filament proteins characteristic of neural differentiation (nestin and vimentin), as well as the astrocyte marker glial fibrillary acidic protein (GFAP) and the neural progenitor marker TUJ-1. We examined the immunomodulatory effects of the CB MSCs after co-culture with murine splenocytes. Whereas spleen cells from normal C57Bl/6 mice exhibited a prominent immunoglobulin M (IgM) response after immunization with the T cell-dependent antigen sheep red blood cells, this response was significantly decreased after incubation with CB MSCs. These data indicate that CB MSCs possess multiple utilities that may contribute to their therapeutic potency in the treatment of neurological disorders.

Animals↗
PubMed2005

Ovarian monocyte progenitor cells: phenotypic and functional characterization.

Leukocytes of the macrophage lineage are abundant in the ovarian tissues and have an important function in both follicular development and regression of postovulatory follicles. In this study, we tested the hypothesis that continuous production of macrophages in the ovarian stroma is maintained by a resident population of progenitors. We established a long-term culture of ovarian follicular stromal cells from BALB/c and green fluorescent protein-transgenic (GFP-TG) C57BL/6 mice. Nonadherent cells were collected and tested for hematopoietic function in vitro and in vivo. Histological and ultrastructural analyses revealed a homogenous population of monocyte-like rounded cells. Nonadherent cells continued to proliferate in culture for several months without senescence. When plated at very low density in methylcellulose, these cells formed colonies consisting of monocyte-like cells. Ovarian monocyte-like cells reacted with CD45, CD11b, CD11c, and Ly6-Gr-1 cell surface markers. A distinct CD45low population within these cells reacted with CD117 (C-kit) surface marker, suggestive of a primitive hematopoietic progenitor. Fifty thousand nonadherent cells failed to provide radioprotection to lethally irradiated mice and thus were not considered to be equivalent to pluripotent hematopoietic stem cells. Ovarian nonadherent stromal cells were positive for alkaline phosphatase but lacked embryonic cell antigens stage-specific embryonic antigen (SSEA-1) and Oct-4. We conclude that in the ovaries, a higher requirement for macrophages is provided by a resident stromal population of progenitors whose progeny is restricted to the production of cells of the monocyte-macrophage lineage.

Alkaline Phosphatase↗
PubMed2005

Umbilical cord blood-derived stem cells and brain repair.

Human umbilical cord blood (HUCB) is now considered a valuable source for stem cell-based therapies. HUCB cells are enriched for stem cells that have the potential to initiate and maintain tissue repair. This potential is especially attractive in neural diseases for which no current cure is available. Furthermore, HUCB cells are easily available and less immunogenic compared to other sources for stem cell therapy such as bone marrow. Accordingly, the number of cord blood transplants has doubled in the last year alone, especially in the pediatric population. The therapeutic potential of HUCB cells may be attributed to inherent ability of stem cell populations to replace damaged tissues. Alternatively, various cell types within the graft may promote neural repair by delivering neural protection and secretion of neurotrophic factors. In this review, we evaluate the preclinical studies in which HUCB was applied for treatment of neurodegenerative diseases and for traumatic and ischemic brain damage. We discuss how transplantation of HUCB cells affects these disorders and we present recent clinical studies with promising outcome.

Animals↗
PubMed2004

Mesenchymal stem cells in autoimmune disease.

Autoimmune diseases afflict more than 3% of the U.S. population. Current therapy for mild to moderate cases is symptomatic, however advanced cases suffer high morbidity and mortality. Advanced patients have benefited from stem cell therapy in the form of bone marrow transplantation in conjunction with high-dose cytotoxic therapy. Broader application of stem cell therapy requires better understanding of how adult stem cells affect development and foster treatment of autoimmune pathologies, and of better ways to manipulate the host immune responses. While extensive research documents the role of hematopoietic stem cells (HSCs) in autoimmune disease, few studies have addressed if and how mesenchymal stem cells (MSCs) contribute to their etiopathology. Recent characterization of MSCs and their role in hematopoiesis and immune modulation suggest that their potential for cell therapy extends beyond their traditional accessory function in HSC engraftment. MSCs contribute significantly to tissue restructuring and immune functioning, in addition to facilitating durable, long-lasting stem cell engraftment. MSCs are relatively easy to obtain and expand in in vitro cultures, rendering them a prime candidate for genetic manipulations for stem cell therapy. They have the potential to differentiate into multiple lineages such as osteoblasts, adipose tissue, cartilage, tendon, and stromal cells. The role of MSCs for autoimmune disease therapy could thus be based both on immune function modulation and contribution to hematopoiesis. In this review, we examine the biology of MSCs, and their potential for cell therapy of autoimmune disease.

Adipose Tissue↗
PubMed2002

Mixed bone marrow or mixed stem cell transplantation for prevention or treatment of lupus-like diseases in mice.

Scientific analyses fortified by interpretations of immunodeficiency diseases as 'experiments of nature' have revealed the specific immune systems to be comprised of T cells subserving cell-mediated immunities plus B cells and plasma cells which produce and secrete antibodies. These two separate cellular systems regularly interact with each other to produce a coordinated defense which permits mammals to live within a sea of microorganisms that threaten the integrity and the survival of individuals. We have shown that bone marrow transplantation (BMT) can be used as a form of cellular engineering to construct or reconstruct the immune systems and cure otherwise fatal severe combined immunodeficiency. When severe aplastic anemia complicated the first BMT which was performed to cure a fatal severe combined immunodeficiency, a second BMT cured for the first time a complicating severe aplastic anemia. Subsequently, BMT has been used effectively to treat some 75 otherwise fatal diseases such as resistant leukemias, lymphomas, inborn errors of metabolism, and genetic anomalies of the hematopoietic development such as sickle cell anemia, thalassemia, congenital neutropenias, and many other diseases. More recently, we have employed BMT in mice both to cure and cause autoimmunities, and, together, these experiments showed that autoimmunities actually reside in the hematopoietic stem cells. We have also found that mixed BMT or mixed hematopoietic stem cell transplantation (HSCT) can be used to prevent and cure the most complex autoimmunities such as those occurring in BXSB mice and in (NZW x BXSB)F1 W/BF1 mice. Untreated, the former develop fulminating lethal glomerulonephritis plus numerous humoral autoimmunities. Mice of the (W/B)F1 strain develop autoimmune thrombocytopenic purpura, coronary vascular disease with myocardial infarction, glomerulonephritis, and numerous autoantibodies. All of these abnormalities are prevented or cured by mixed syngeneic (autoimmune) plus allogeneic (normal healthy) BMT or mixed peripheral blood HSCT. Thus, the most complex autoimmune diseases can be prevented or cured in experimental animals by mixed syngeneic plus allogeneic BMT or HSCT which produce stable mixed chimerism as a form of cellular engineering.

Animals↗