**1. Introduction**

A limited number of pluripotent stem cells are mainly located in the bone marrow, and give rise to all blood cell 1ineages. Because of their relatively short lifespan, circulating cells must be continually replaced in living body throughout the life. The task performed by hematopoietic stem cells is shared in two main features, that is, the capacity of regeneration which prevents depletion of the cells and the ability of preservation of blood homeostasis. The mechanisms behind the critical choice between lineage-commitment and maintenance of the stem-cell pool involve a number of complex interactions between hematopoietic progenitor cells at different stages of maturation, stromal cells and their extracellular matrix, as well as a variety of stimulatory or inhibitory cytokines provided by the microenvironment.

Hematopoietic growth factors were first identified in the 1960s as soluble agents produced in spleen, uterus or lung, and found to maintain the formation of differentiated colonies from hematopoietic progenitor cells in semisolid culture systems. Hence they were named colony-stimulating factors, CSFs (Schneider and Dy, 1999). Most of these molecules have been purified and their genes have been sequenced. They are currently available in recombinant form and have been used with success in clinical trials.

Hematopoietic growth factors or CSFs can be divided into two categories, according to their target cell specificity (Figure 1). One group comprises the factors whose activity is relatively restricted to particular cell types, such as macrophage colony-stimulating factor (M-CSF) for macrophages, granulocyte colony-stimulating factor (G-CSF) for neutrophils, interleukin-5 (IL-5) for eosinophils and B cells, and thrombopoietin (Tpo) for megakaryocytes and erythropoietin (Epo) for the erythroid lineage. The second category of growth factors has a

© 2012 Hayashi, licensee InTech. This is an open access chapter distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2012 Hayashi, licensee InTech. This is a paper distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2012 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

relatively wide spectrum of activities, such as IL-3 and granulocyte-macrophage colonystimulating factor (GM-CSF). The factors target a heterogeneous population of cells, including both primitive and lineage-committed progenitors. Action of these two molecules can be modulated by a number of cytokines which are not essentially growth factors. Among these, IL-1, IL-6, IL-9, IL-1l and leukemia inhibitory factor (LIF) are involved. An interleukin 6 class cytokine or stem cell factor (SCF) plays a particularly important role in the amplification of early stem cell commitment. IL-7 is also noteworthy in this context, with respect to its crucial role in lymphopoiesis, as evidenced by the strong lymphopenia in IL7 deficient mice. Hematopoiesis can be also regulated negatively by a heterogeneous set of molecules, such as interferon, tumor necrosis factor-alpha (TNF-α), transforming growth factor beta (TGFβ) and compounds like prostaglandins, ferritin and lactoferrin.

Proliferation and Differentiation of Hematopoietic Cells and Preservation of Immune Functions 121

In the chapter, we focus on relations and networks of cytokines, induced by ingesting *in-vivo* study of *Spirulina* and by *in-vitro* cultured cells, to differentiation of hematopoietic cells and preservation of immune functions, and discuss the possibility of their medicinal application

*Spirulina platensis* is a helicoidal filamentous blue-green alga (cyanobacterium) and has a history of being used as food for over a thousand years, and has been commercially produced for more than 40 years as a food supplement (Ciferri, 1983; Gershwin and Belay, 2008). *Spirulina platensis* is prokaryote and belongs to the class Cyanophyceae, or Cyanobacteria. In its commercial use, the common name, *Spirulina*, refers to the cyanobacterium, *Arthrospira platensis*, and is a whole product of biological origin. In its taxonomic use, *Spirulina* is a name used to describe mainly two species of Cyanobacteria, *Arthrospira platensis* and *A. maxima*, which are commonly used as food, dietary supplement, and feed supplement (Vadiraja et al., 1998) . These and other *Arthrospira* species forming helical trichomes were once combined and classified into a single genus, *Spirulina* (Geitler, 1932). Before Geitler, on the basis of the presence of septa or division in the trichomes, the two genera were placed separately, that is, the *Spirulina* species being without septa and the *Arthrospira* species with septa. Recent morphological, physiological, and biochemical studies have shown that these two genera are distinctively different and that the edible forms commonly referred to as *Spirulina platensis* have little in common with other much smaller species. This distinction has been also based on results from the complete sequence of the 16S ribosomal RNA gene and the internal transcribed spacer (ITS) between the 16S and 23S rRNA genes determined for two *Arthrospira* strains and one *Spirulina* strain (Nelissen et al., 1992) showing that the two *Arthrospira* strains formed a close cluster distant from the *Spirulina* strain. Blue green algae *Spirulina platensis* (*Arthrospira platensis*) is gaining more and more attention as a nutraceutical and source of potential pharmaceuticals. *Spirulina* is known to have nutritional advantages of high-quality protein contents and other components such as vitamins; minerals, and essential fatty acids, including γ-linolenic acid, and β-carotene (Belay et al., 1993) , and has been approved its safety in the report from United Nations International Development Organization, UNIDO (Chamorro-Cevallos, 1980). Moreover, sulfated polysaccharides, called calcium-spirulan (Ca-Sp) and isolated from a hot-water extract of *Spirulina*, exhibit immunomodulatory activity and inhibit metastasis of melanoma cells to the lungs (Mishima et al., 1998) , and can also inhibit virus entry (Hayashi et al., 1996). Immolina, a high-molecularweight polysaccharide fraction of *Spirulina*, promotes chemokine expression in human monocytic THP-1 cells (Grzanna et al., 2006). *Spirulina* contains phycocyanin (CPC; Cphycocyanin), a blue, 270-kDa photosynthetic pigment protein, which accounts for

approximately 15% of the dry weight of *Spirulina* (Ciferri, 1983).

involving immune functions have also been reported (Belay, 2002).

Recently, more attention has been given to the study of the therapeutic effects of *Spirulina*. In addition to its effectiveness in reducing hyperlipidemia, diabetes, and high blood pressure in humans and animals, anti-viral and anti-cancer effects of orally administered *S. platensis*

for sustaining a healthy state.

**2.** *Spirulina*

The precise function of cytokines during constitutive hematopoiesis in a healthy organism is still unclear, although much evidence has been accumulated from the study using genetically modified mice. The purpose of hematopoiesis, however, is not only the maintenance of homeostasis, but also a rapid and controlled response to stress situations. The immune response induced by infection, the number of circulating white blood cells can be remarkably increased (Schneider and Dy, 1999). In the process, the cytokines generated by sensitized lymphocytes and activated cells of the immune system play a crucial role in the recruitment and the differentiation of hematopoietic cells.

**Figure 1.** Simplified haematopoietic differentiation scheme and cytokines (modified from Elk and Dy, 1999)

In the chapter, we focus on relations and networks of cytokines, induced by ingesting *in-vivo* study of *Spirulina* and by *in-vitro* cultured cells, to differentiation of hematopoietic cells and preservation of immune functions, and discuss the possibility of their medicinal application for sustaining a healthy state.
