Developmental and Stem Cell Biology in Health and Disease

The question of how could a single cell develop into an animal has been asked for centuries. Since the seventeenth century, epigenesis and preformation theories have been two persistent ways seeking to explain the development of individual organic form. Nowadays, it is proved that both zygote’s genome and cytoplasmic determinants control development. Cell division, cell differentiation and morphogenesis then take place. To build an animal’s body, fertilization is the first step where a diploid number of chromosomes is restored. Fusion of egg and sperm activates the egg. Three stages then follow; cleavage, gastrulation and organogenesis. Cleavage pertains to the repeated mitotic division of a zygote into smaller cells, blastomeres. More cleavage results in a solid ball of cells called morula. With further cleavage a hollow ball of cells, the blastocyst, is produced. Gastrulation is a necessary event in developing a multicellular animal. During this process, the embryonic cells are rearranged to form a three layered embryo. Accordingly, cells acquire new positions enabling them to interact with cells that were initially far away from them. Many inductive interactions then occur to start neurulation and organogenesis. Early in vertebrate organogenesis, the notochord which forms in mesoderm leads to neural plate induction from the covering ectoderm. This neural plate forms the neural tube that will become the central nervous system. All other organs develop from folds, splits and condensations of cells. Thorough understanding of early mammalian development has initiated the era of embryonic stem cell generation and its use in medicine.

Recent developments have revealed more about the signaling pathways governing hematopoietic stem cell (HSC) fate; several developmentally conserved pathways were identified, including Notch, Smad pathways, Sonic hedgehog (Shh), and Wingless-type (Wnt). These findings contribute to our understanding of HSC regulation and provide information of interactions within the bone marrow environment where HSCs reside. The signaling pathways that contribute to HSC regulation are further discussed in this chapter.

Drosophila is a genus of flies of the family Drosophilidae. It comprises of 1579 described species. Stem cell present in stem cell niche and interacts to regulate cell fate. Many factors act on embryonic stem cells during embryonic development to alter gene expression, and induce their proliferation or differentiation for the development of the fetus or larvae.

Stem cell niches maintain adult stem cells in a quiescent state. After tissue injury, the surrounding micro-environment induce stem cells to promote either self-renewal or differentiation to new tissues. Various factors are important to coordinate stem cell characteristics within the niche: cell-cell interactions between stem cells, as well as interactions between stem cells and neighbouring differentiated cells, interactions between stem cells and adhesion molecules, extracellular matrix components, the oxygen tension, growth factors, cytokines, and the physicochemical nature of the environment including the pH, ionic strength (e.g. Ca2+ concentration) and metabolites, like ATP, are also important. During development, stem cells and niche may induce each other and alternately maintain each other during adulthood.

Stem cells are unique, rare cell types that exist within many various life forms; they have been identified in both the plant and the animal kingdoms. These cells possess two distinguishing characteristics: the capacity for self-renewal in order to preserve the stem cell pool, and pluripotency, in which they differentiate into specialized cells when particular signals are given [1]. Due to these defining qualities, stem cells have been found to be primordial players during development, tissue repair and regeneration after injury, and healthy homeostatic cell turnover. They are, therefore, a crucial driving force for fast-expanding fields of regenerative medicine and functional tissue engineering [2]. The substantial building blocks of life are embryonic stem cells (ESCs). During early embryogenesis, ESCs that have their origin in the developing blastocyst’s inner cell mass (ICM) contain the capacity for pluripotency. Thus, they have the ability to become any type of cell that is required to form an entire organism. Adult stem cells are another type of stem cells that are uncommon tissueresident cells; they are essential for the establishment, maintenance, and repair as well as regeneration of highly specialized tissues in multicellular organisms [3].

The activation, survival, and quiescence of stem cells (SCs) are dependent on signaling within their niche or microenvironment. There are many types of SCs and SC niches that can be found in the human body. A single organ may contain more than one niche to accommodate for both slow and fast cycling SC populations. It appears that many SC niches possess similarities in both their cellular and molecular components. This chapter focuses on cellular organization, key molecular regulators, and the role of SC niches in aging and cancer.

Stem cells are known to have a paramount function in tissue regeneration and also the proliferation of cancer, and the ability that stem cells have to self renew allows them to differentiate and to regenerate injured tissues. More importantly, this capacity to self renew allows cancer stem cells to proliferate and promote cancer. Mesenchymal stem cells are multipotent cells that have the ability to differentiate into various cell types including; adipocytes, osteoblasts, and chondrocytes. These cells are known to regulate the healing of injuries and wounds and to activate cancer growth by secreting bioactive factors through paracrine signaling. Through scientific research, there is evidence that tissue specific and cancer stem cells also affect their surroundings through paracrine mechanisms, which would permit stem cells to facilitate wound recuperation and tumor proliferation, respectively. Because of this important connection, further investigation of the paracrine mechanisms by stem cells would ameliorate cancer treatment and cast light on the mechanisms of tissue regeneration.

Tumorigenic cancer stem cells [CSCs] are multipotent cells that found together with their nontumorigenic variants in the same clone. Although sharing the same genetic battery, CSCs and their non-tumorigenic progenies respond differently to micro environmental stresses. Thus, hypoxia, inflammation, low pH, shortage in nutrients and cancer therapies result in broad spectrum of changes in signaling pathways. These facts paved the road to a new era in cancer treatment strategies where inhibiting CSCs specific pathways are combined with traditional therapies of bulk tumor cells. Despite the promise such combination brought to cancer cure improvement, resistance to some to some CSCs-related therapies is noticed. Thus, this review focuses on the mechanisms that may involve in such resistance including drug efflux by ABC transporters, activation of aldehyde dehydrogenase and developmental pathways, enhanced DNAdamage response and autophagy and microenvironmental conditions. This review discusses as well the possible therapeutic strategies for improving cancer treatment.

Neurodegenerative diseases are a major concern of our present time and which underpin the ageing era that invades the world. The Neurodegenerative diseases are caused by certain neuronal loss in specific regions of the brain. Alzheimer’s disease (AD) and Parkinson’s disease (PD) are some of the examples of the neurodegenerative diseases that have no fundamental cure available. Some drug treatments can alleviate the symptoms associated with the neurodegenerative diseases. However, they do not tackle the main pathological factors and cannot be clinically suitable for all patients. Moreover, they are not affordable by all patients as a long term medicine. Therefore, developing new and effective medications for AD and PD is deemed necessary. Recent research has aimed at developing therapies that modify the disease. These therapies perform their actions by interacting with the pathophysiologic cascade in order to postpone the disease onset or prevents the progression from occurring on a fast pace. Embryonic and Adult stem cells have demonstrated high therapeutic potential for tissue regeneration. As well, cell replacement therapy would introduce cure for these neurological disorders. Treatment of neurodegenerative diseases using stem cell transplantation has attracted a great deal of attention lately. This is owing to the fact that stem cells are readily available, can be easily expanded in culture, and can have sustainability when transplanted for relatively long periods of time. Moreover, the growth factors and cytokines released by stem cells facilitate neo-vascularization of damaged tissue leading to neurogenesis, as well as affording anti-inflammatory, antiapoptotic, and anti-oxidative effects among other reparative responses. From this point of view, stem cell therapy will provide a powerful and effective cure for most of neurodeteriorative diseases in the near future.

The composition of bone is a connective tissue of particular cells, fibers, and ground substance. One of the well known bone diseases, which featured by low bone mass and bone fragility, is osteoporosis. Nowadays, there is a fast ongoing revolution in stem cells either derived from blood or tissues postnatally. The present chapter has provided a principal understanding about the importance of mesenchymal stem cells (MSCs) in the management of osteoporosis. This might be attributed to their direct ability to generate osteoprogenitors and osteoblasts via their influence on osteoclastogenesis. In addition, the usefulness of the MSCs when combined with calcium phosphate composite as an osteoinductive material in osteoporosis stem cell therapy has been described in the current chapter. On the other hand, self-renewal dental pulp stem cells are now known as being important to the regeneration of dentine. Development of novel tissue engineering strategies is mainly based on excellent awareness of the stem cells nature to determine their potentialities. This novel way of bone disease therapy may provide an innovative generation of new strategies to tackle bone diseases.

In this chapter, the aim is to shed the light if the new era of stem cells can play a role in the field of Medical Parasitology. We will try to answer certain questions. First; would parasites be friends or foes in the process of stem cell culture and therapy? Another question is that; can stem cells be a novel therapy against the notorious parasites that attack the human being and heal the permanent damage that some parasites may induce in organs? Finally, could the parasite stem cells be a potential target for new anti-parasitic therapy, especially in resistant chronic debilitating parasitism?