Animal and Plant Stem Cells

This chapter intends to give the audience a basic idea on normal and cancer stem cells, as two essential types of cells in stem cell phenomenology connected by the same feature—“stemness.” This is an introductory conceptual consideration of what these cells are and where are their similarities and differences. The chapter discusses normal and abnormal mechanisms that are working in both type of these cells and make them different. General features of both cell types are given in condensed manner. The development of methodology for their isolation, purification, and segregation from other cell types in normal and cancerous tissues is presented. New methods such as magnetic beads separation, magnetic levitation, detection of microspheres in CSC, the confirmation of CSC entity through injection of the cells in NOD/SCID mice, are described. The impact of the concepts upon development of a new movement in cancer therapy, cancer stem cell targeted therapy is explained.

This chapter is clarifying essential characteristics of stem cells which otherwise one cannot find in other types of cells and why they are regarded so extraordinary, particular, and unique. Their characteristic features of self-renewal and plasticity make them necessary for everyday life of the body which is in constant renewal and recovery and must be maintained in perfect homeostasis in order to stay healthy and alive. The other two features, although present in cells other than stem cell: proliferation and differentiation, are the features that enable them to manifest their extraordinary capacity to exert the building blocks of the tissues and organs which is actually, their fundamental role. We have also emphasized heterogeneity of stem cell populations as well as their “hypoxic” nature.

This chapter describes particular stem cell sources and types of these cells. It emphasizes the distinction between ESCs and FSCs versus adult tissue stem cells. It also comments the questions that are not answered yet, despite the application of stem cells from different sources in clinical arena.

Stemness is still a contraversive entity and the definition is evolving. It can roughly be defined as the most primitive cell state capable of transdifferentiating into divergent functional cell lines. Different stem cells express different stem cell markers which are hallmarks of these cells together with adequate functionality. Sometimes the cells possess/express the markers (phenotype) but the function is lacking and therefore they cannot be considered stem cells. Markers are protein products of clonal expansion, during self-renewal of stem cells, where the entire energy is invested in their multiplication. They are permanent labels of stemness and different in different stem cell types from different sources. Here we are presenting the examples of stem cell markers known so far.

Essential stem cell signaling pathways are described and graphically presented for ESC and adult HSC and MSC. Two distinguishing characteristics of embryonic stem cells (ESCs) are totipotency and the ability to self-renew. These traits, which allow ESCs to grow into any cell type in the adult body and divide continuously in the undifferentiated state (self-renewal), are regulated by a number of cell signaling pathways. Adult stem cells such as HSC and MSC have different pathways involved. This can partially explain their restriction of the potency. Up-to-date knowledge on signaling mechanisms and genetic regulation in human stem cells is provided. Transcriptional and posttranscriptional control is described that enable maintaining the boundaries between pluripotent stem cells and differentiating descendants. The involvement of signaling molecules is emphasized with corresponding schematic view. Several key regulators of stem cell maintenance revealed corresponding genetic and humoral regulation which is briefly presented. Similarities at the molecular level between different animal stem cells, in terms of regulation and maintenance, are depicted.

The chapter describes the ways to expand the insufficient number of stem cells into desired, for clinical application. At first, it was regarded that for example, cord blood stem cells should not be stored at all, since their total yield was low. However, with the time, the methods for expansion have been developed and strongly supported the use of stem cells from different sources in clinical arena. Several approaches to expansion mainly through propagation in culture, are briefly described.

This chapter will discuss origin, classification, features of stem cells and fundaments of stem cell therapy as the segment of cellular-based therapy. Generally, the Stem Cell (SC)—compartment is divided into embryonic and tissue specific or adult SCs. Paul Niehans, M.D., (1882–1971), the originator of cell therapy, wrote: “Cellular therapy is a method of treating the whole organism on a biological basis, capable of revitalizing the human organism with its trillions of cells by bringing to it those embryonic or young cells which it needs. Cells from all organs are at our disposal; the doctor’s art is to choose the right cells. Selective cellular therapy offers new life to the ailing or diseased organism.” The concept of very small embryonic-like stem cells (VSELs) and their phenotypic and functional characteristics are discussed in the light of recent conflicting data. The differences between two adult stem cell compartments (hematopoietic and non-hematopoietic) within the adult bone marrow, (BM) and distant organs are emphasized. The crucial criteria for distinction between these two different pools of stem cells {hematopoietic stem cells (HSCs)}, and VSELs, are presented “hallmarking” VSELs as a separate entity. A possible explanation for the presence of these cells in the adult bone marrow of humans and them impacting stem cell regenerative purposes are summarized, as they are also found in the cord blood (CB). Certain organs/tissues involvement in the VSEL generation and/or storage is also discussed. The experimental approach to this area is analysed, followed by brief description of separation, purification and identification of this cell population in mice and humans. The critical controversies in findings regarding VSELs within the overall stem cell concept/stemness are analysed in depth. The functional role and perspectives of stem cell therapy in the clinical arena using this existing stem cell primitive ancestor are envisioned with regard to their fundamental traits as a great challenge and inspiration for future studies.

The toti—and pluripotency ascribed to ESC were considered the unique qualities of these cells making them the pattern of choice for regenerative and reparative purposes. However, John Gurdon and Shinya Yamanaka, have discovered that nucleus of somatic adult cells can be reprogrammed to lead the cells into their pluripotency [1‐3]. The methods of reprogramming, with focus on the use of nanoparticles, the features of i [1‐3] PCs and their significance for clinical application are described and discussed in this chapter.

The chapter is describing two CSC concepts that are currently actual: the concept of clonal evolution and the concept of cancer cell. The idea is the CSC is tumorigenic as the result of their stemness, and therefore should be targeted by specific approach.

This chapter discusses the basics of vital processes in cytosolic and mitochondrial compartments: metabolic events, and their deviation in cancer cells, based upon metabolic reprogramming which is today regarded as the essence of dramatic mechanisms in cancer stem cells. The genetic mechanisms were so much in trend that the work of Warburg, Pasteur, Crabtree, and Racker which was almost forgotten for several decades, emerges now again as inevitability linked to specificities of cancer stem cell metabolism detected in their time. Disturbances in glycolysis and respiration as well as mitochondrial changes such as uncoupling of respiration and oxidative phosphorylation are today given second look. And with new set of information, the cancer stem cell could be looked at from another angle, explained in this chapter. The metabolic theory of CSC and its roots are described.

The concept of cancer stem cells has inevitably inspired the concept of targeted CSC therapy. Recent identification of surface markers and understanding of molecular feature associated with CSC phenotype helped with the design of effective treatments. This concept envisions CSC as a unique target that should be destroyed with either physical, pharmacological, immunological, or even combined modalities, which do not affect normal cells. This chapter is a consideration of novel strategies aimed at targeting CSCs. The ideas discussed in this review can be summarized as a set of propositions for novel therapeutic approach.

This chapter will deal with fundamentals of typization for the choice of donor and essential principles unclufing immunological genetic basis for that. The role of MSH and HLA systems in diversification of these mechanisms is described and clarified. The significance of good match for successful engraftment is also emphasized. Some aspects of the matter are illustrated.

This chapter is focused to engraftment and use of genetic markers in cellular therapy. It is concisely explaining conditions for homing in recipient and the significance of both in Tissue Engineering and cellular therapy.

There is a tight bond between nanotechnology and stem cell research reflected in many directions. This chapter is a brief description of direct and indirect relationships operating in nuclear reprograming, magnetic bead technology, drug delivery and targeted drug delivery, cancer stem cell therapy, reduction of drug toxicity, remote control, etc.

A very brief overview on five important aspects of stem cell therapy are given in this chapter. The chapter is dealing with criteria for optimization of the pattern for cell-based therapies, extent of regeneration in animals and humans, nuclear reprogramming as a possible modality for treatment with pluripotent adult cells, significance of expansion, and essential role in Tissue Engineering.

The chapter is dealing with expectations and results related to stem cell therapy. It summarizes pros and cons for stem cell therapy, use of particular patterns, and final output in different diseases. The controversive debate about adult stem cell pluripotency is underlined. The encouraging results are presented and critical remarks stated.

Physical aspects of targeted therapy approaches especially of CSCs are the topic of the cancer stem cell research. Whether they will appear to be better then classical chemo and radiotherapy, or as additional treatment, is still a matter of investigation. This is a brief summary with respect to possibilities with emphases on biophotones.

A brief summary on entire matter of animal stem cells is given. The outlines of future research directions are roughly drawn.

This chapter gives definition of plant stem cells, which are located in the organized structures called meristems. Definition, description, and function of different types of meristems (primary and secondary meristems), and their location in a plant are provided.

The structure and organization of the shoot and root apical meristems is presented. Their functional zones and mechanism of functioning are described. The shoot apical meristem is presented as a dynamic structure that changes during leaf and stem formation. The generation of primary roots from the primary (apical) root meristem and of secondary roots from the secondary root meristems is described and schematically presented. Finally, similarities of plant stem cells in different types of meristems, at the molecular level, are presented.

In the plants exhibiting secondary growth (most trees, shrubs and some herbs), besides primary meristems there are secondary (lateral) meristems, which are described in this chapter. Accent is given on the lateral meristems in the stems of woody plants.

This chapter describes the effect of the external factors such as elevated CO₂ or mechanical sensations on the activity of meristems, and adaptive meaning of these relations. The role of modeling in such kind of studies is mentioned.

This chapter presents the up-to-date knowledge on signaling mechanisms and genetic regulation in plant meristems. First, regulation in shoot and root apical meristems is given. Transcriptional and posttranscriptional control is described, that enable maintaining the boundaries between pluripotent stem cells and differentiating descendants. The involvement of signaling molecules, such as hormones auxin and cytokinines, is presented with corresponding schematic view. The regulation in lateral meristems is also described, where several key regulators of stem cell maintenance revealed surprising similarities to the apical meristems. Regulation of grass meristems is further described, since many agricultural plants belong to this group. The shoot architecture in such plants is critical to reproductive success, and thus to agronomic yield. Phyllotaxy, or pattern of leaf initiation, and floral induction is described, since they are important for the members of the grass family. Corresponding genetic and hormonal regulation is briefly presented. Similarities at the molecular level between different plant stem cells, in terms of regulation and maintenance, are depicted.

This chapter describes the role of primary and secondary growth and of related meristems, in establishing the basic body plan of the plant. The evolution of secondary growth and role of corresponding meristems in adaptations to terrestrial life is explained.

This chapter describes advantages of cultivation of plant stem cells as a source of biologically active compounds for potential applications, over wild plants collection, plant cultivation, or non-meristematic plant cell culture propagation.

The energy metabolism in animal normal and cancer stem cells is described. Mitochondria in plant stem cells are characterized, with focus on the specific architecture of mitochondria in shoot apical and leaf primordial meristems, and on the role of dysfunctional mitochondria in meristem regulation. A description of molecular differences in mitochondria between plants and animals is given.