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3 Archivum Immunologiae et Therapiae Experimentalis

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Neurokinin receptors: relevance to the emerging immune system

100%

Kang H. S. , Trzaska K. A. , Corcoran K. , Chang V. T. , Rameshwar P.

2004

tom 52

nr 5

338-347

The adult bone marrow (BM) is the major site of the emerging immune system. Hematopoiesis is the process whereby immune cells are generated from a finite number of hematopoietic stem cells. Hematopoiesis is regulated by soluble mediators and intercellular interactions. A major regulatory mechanism of hematopoiesis involves bidirectional crosstalk with the neural system. This communication mainly occurs by the release of neurotransmitters from innervated fibers. The neurotransmitters interact with specific receptors on BM resident cells and release other hematopoietic regulators such as cytokines. Together, the neurotransmitters and cytokines form a complex network to regulate hematopoiesis. Among BM resident cells, the stromal cells are particularly relevant for two reasons: 1) they represent non-neural sources of neurotransmitters, and 2) stromal cells express specific receptors for neurotransmitters. This review focuses on the hematopoietic effects of neurotransmitters belonging to the tachykinins. The two major tachykinins focused in this review are substance P and neurokinin (NK)-A, 11 and 10 amino acid peptides. In BM, the tachykinins interact with two major NK receptors: NK-1 and NK-2. These two receptors appear to limit tachykinin-mediated effects on hematopoiesis. The central roles of NK receptors within a network comprising of cytokines and tachykinins are reviewed.

Simultaneous transplantation of two allogeneic units of cord blood in an adult patient with acute myeloblastic leukemia. A case report

88%

Wiktor-Jedrzejczak W. , Rokicka M. , Urbanowska E. , Torosian T. , Graczyk-Pol E. , Tomaszewska A. , Krol M. , Paluszewska M. , Gronkowska A. , Ziarkiewicz-Wroblewska B. , Jolkowska J. , Witt M.

Archivum Immunologiae et Therapiae Experimentalis

2005

tom 53

nr 4

364-368

The major obstacle to the therapeutic use of hematopoietic transplantation is the unavailability of matched, unrelated marrow donors for the large number of potential patients, although all of them have the chance to find sufficiently matched, unrelated cord blood units. However, the use of cord blood as a source of cells for transplantation is limited by its cell number, usually below 1 billion, which allows for routine transplantation only in children weighting less than 30 kg, while most potential recipients possess a higher body mass. This led to the idea of the simultaneous use of several units of cord blood which, combined, would fulfill the requirements for the necessary cell number for an adult recipient. We attempted to simultaneously transplant an adult patient with refractory acute myeloblastic leukemia utilizing two different cord blood units, one fully matched and one mismatched at one locus. The patient became reconstituted with only one unit, the mismatched, as determined using microsatellite markers, and had no signs of relapse of leukemia. Unfortunately, he died of persistent fungal (brain aspergilloma) infection on day +103. The successful engraftment may suggest that a method based on the principle of using more than one cord blood unit for transplantation is feasible in large adult patients and may reach routine application.

Immunological properties of mesenchymal stem cells and clinical implications

88%

Patel S. A. , Sherman L. , Munoz J. , Rameshwar P.

2008

tom 56

nr 1

1-8

The rapid evolution of experimental data has acknowledged the critical relevance of immune biology in stem cell research. It appears that efficient transfer of stem cells to patients requires robust analyses of the immune properties as well as the responses of the stem cells to immune mediators. This review discusses the biology of adult human mesenchymal stem cells (MSCs) in the context of immunology. MSCs are pluripotent, self-renewing cells with the potential for tissue regeneration, for example the repair of bone, cartilage, tendon, ligament, skeletal muscle, and cardiac muscle. MSCs have also been shown to transdifferentiate into cells of ectodermal origin, such as neurons. MSCs are located in perfused areas of adult bone marrow, whereas hematopoietic stem cells are located in poorly perfused areas of the same organ. MSCs show bimodal, i.e. anti-inflammatory and immune-enhancing, immune responses. MSCs also regulate immune responses such as the regulation of antibody production by B cells, alterations in T cell subtypes, and immune tolerance of allogeneic transplants. MSCs also have the potential for gene delivery. This review explores the diverse clinical potential for MSCs and discusses the limitations and advantages of their immunomodulatory properties.