Table of Contents
Stem cells are originally defined in the hematological system, but recently have been found in a multitude of other sites. These cells all share the same features of self-renewal and multipotentiality and different types and therapeutic strategies have been defined with respect to the nervous system In mammals, there are two broad types of stem cells: embryonic stem cells and adult stem cells which are found in various tissues. There are three known accessible sources of autologous adult stem cells in humans: Bone marrow, Adipose tissue (fat cells) and Blood. Stem cells or mother cells have the remarkable potential to develop into many different cell types in the body. Serving as a form of remedy system for the body. When a stem cell divides, each new cell was the prospective to either remain a stem cell or become another type of cell with a more specialized function, such as brain cells. Stem cells differ from other kinds of cells in the body. All stem cells in any case of their source have three general properties:
- Capable of dividing and renewing themselves.
- Unspecialized; and they can give rise to specialized cell types.
- Unlike blood cells and nerve cells – which is not normally replicated themselves – stem cells may replicate many times.
In the last two decades the transplantation approach, by means of stem cells of different origin, has been recommended for the treatment of neurological diseases. The choice of different animal models and the differences in techniques of stem cell preparation make it difficult to compare the results of transplantation experiments. Moreover, the translation of these results into clinical trials with human subjects is difficult and has so far met with little success. Neurodegeneration is the cumulative loss of structure and function of neurons, including death of it. Many neurodegenerative diseases including Parkinson’s and Alzheimer’s occur as a result of neurodegenerative processes. One of the landmark events in neuroscience research was the establishment of neural stem cells as a life-long source of neurons, a concept that smash the tenet that the nervous system lacked regenerative power. Stem cells endure the pliability to generate and repair nervous system function. So, the present state of the art focuses on three objectives:
- (1) toprovide a review on the different types of stem cells and how they have been applied to neurological disease in general,
- (2) to synthesize information on understanding Alzheimer’s disease and Parkinson’s disease through the investigation of the rare, clearly inherited forms of these diseases and
- (3) to synthesize further important discoveries and novel therapies based on the application of these powerful cells.
INTRODUCTION
Neurodegenerative diseases affect so many people worldwide, Alzheimer’s disease and Parkinson’s disease are the most normal types. More than five million people are living with Alzheimer’s disease, and at least 500,000 one live with Parkinson’s disease, although some estimates are much higher. Neurodegenerative diseases occur when nerve cells in the brain or peripheral nervous system lose function over time and ultimately die. Although treatments may help relieve some of the physical or mental symptoms associated with neurodegenerative diseases, there is currently no cure or way to slow disease progression.
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It is an understatement to say that practical applications of stem cell research have been game changers for the field of neuroscience. When the term ‘‘stem cell’’ was used 25 years ago, the context was typically adult tissue homeostasis and mouse genetics. Today it would be difficult to consider adult neurogenesis without reference to endogenous neural stem cells. Neural stem cells (NSCs) are capable of self-renewing, proliferating, and differentiating into cells of the neural lineage, including neurons and oligodendroglia. While the neurological deficits from congenital lesions may not be completely docile to any sort of medical therapy, stem cells may offer a regeneration of neurons from the place where the growth has stood. Scientists have been working on the process of utilizing stem cells to accomplish the damaged cells. (Gore A. et al., 2013; Yoo J. et al., 2011) the recent advances in cultivation of human embryonic stem cells and the recognition of plasticity in the human nervous system have created new visualizations into the possibility of using stem-like cells to treat neurological conditions.
Though at present, very little experimental work has the potential to reach clinical trial level, there is substantial evidence to believe that stem cells can act as recovery of damaged neurons by reducing inflammation. Stem cells have the ability to produce neurotrophic or immunosuppressive factors thus forming a convenient milieu for brain tissue repair and long-term survival of transplanted cells in the central nervous system (Lescaudron L. et al., 2012). In animal studies, benefits of stem cell-mediated gene transfer of therapeutic genes such as neurotrophic factors and enzymes have been demonstrated (Kim Su. et al., 2013). Overall, neural progenitor/stem cells present a promising therapy strategy in the treatment of various neuronal diseases.
STEM CELLS
Stem cells load a great expectation for treating different neurological diseases, due to its ability to maintain self – renewal and differentiate to various cell types. This ability to mature and differentiate to different phenotypes contains composite events which can be affected by various regulatory molecules (Tohill M. et al., 2004). Non-neuroectodermal stem cells as bone marrow, blood and dental pulp can induce neurogenesis when attached along with neural stem cells. The neuro-regenerative influence of stem cells can be through a number of mechanisms. Stem cells can act through inducing endogenous neurogenesis and angiogenesis through its tropic effects (Huang WH. et al., 2013).
Mesenchymal stem cells in addition to its alteration ability can secrete neuroregulatory mediators that aid in neurogenesis, immunomodulation, inhibition of apoptosis and glial scar formation, neural as well as glial cell survival and lastly neuroprotective activities on different levels. Human mesenchymal stem cells are adult stem cells, which have the capability for multi-lineage differentiation, open-handed increase to a variety of mesenchymal phenotypes such as osteoblasts (bone), adipocytes (fat), and chondrocytes (cartilage). Mesenchymal stem cells generally reside in the bone marrow stroma, but have also been found in adipose, liver, peripheral blood, umbilical cord blood, and other mesenchymal tissues. Owing to their ability for self-renewal over long periods of time and the ability to differentiate into specialized cells, interest in understanding the biology of stem cells cultures has improved, especially for their therapeutic potential for a variety of diseases.
CLASSIFICATION OF STEM CELLS ON THE BASIS OF POTENCY
Stem cells can be categorized by the ambit to which they can differentiate into different cell types. These four main categorizations are totipotent, pluripotent, multipotent and unipotent. The ability to differentiate into all probable cell types. Examples are the zygote formed at egg fertilization and the first rare cells that result from the division of the zygote. The ability to differentiate into almost all cell types. Examples contain embryonic stem cells and cells that are resulting from the mesoderm, endoderm, and ectoderm germ layers that are formed in the beginning stages of embryonic stem cell differentiation (Thomson JA. et al.,1998). The ability to differentiate into a strictly related family of cells. Examples include hematopoietic (adult) stem cells that can become red and white blood cells or platelets.
The oligopotent stem cells are similar to the prior category multipotent stem cells but they become further restricted in their capacity to differentiate (Shamblott MJ. et al., 1998). The ability to only produce cells of their own type, but have the property of selfrenewal wanted to be labeled a stem cell. Examples contain (adult) muscle stem cells. CLASSIFICATION OF STEM CELLS ON THE BASIS OF THEIR SOURCES The easy way to classify stem cells is by dividing them into two types: Early or embryonic and mature or adult. Early stem cells, often named embryonic stem cells, are found in the internal cell mass of a blastocyst after nearly five days of development. Mature stem cells are found in specific mature body tissues as well as the umbilical cord and placenta after birth. Embryonic stem cells are selfr-eplicating pluripotent cells that are actually deathless (Roszek K and Czarneka J 2014). They are derived from embryos at a developing stage before the phase of implantation would normally occur in the uterus (Avasthi, R. N. et al., 2008). Adult stem cells are undifferentiated totipotent or multipotent cells, found throughout the body after embryonic development, the primary roles of adult stem cells in a living organism are to maintain and repair the tissue in which they are found. Unlike embryonic stem cells, which are defined by their origin. The origin of adult stem cells in some mature tissues is still under investigation.
Recently, a third type of stem cell, with properties parallel to embryonic stem cells, has emerged (Ulloa-Montoya. et al., 2005). Growing cells in the laboratory is known as cell culture. Human embryonic stem cells are generated into a plastic laboratory culture dish that has a nutrient broth known as culture medium. The cells split up and disseminate over the surface of the dish. The plated cells survive, divide and redouble enough to crowd the dish and then removed softly and plated into fresh culture dishes. Once the cell line is established, the original cells produce millions of embryonic stem cells. Embryonic stem cells that have proliferated in cell culture for six months without differentiating. At any stage in the process, batches of cells can be frozen and shipped to other laboratories for further culture and experimentation (Singec, R. et al., 2007).
The target of regulation on cell culture practice is to promote the maintenance of high standards and to reduce uncertainty in the development and application of animal and human cell and tissue culture procedures. The standardisation of in vitro systems begins with the original animal or human donor and the cells or tissues derived, and also includes their subsequent manipulation, maintenance, and preservation. Standardisation is a hard task, because cells are prone to change in culture. The availability of quality-controlled stocks of cells and tissues, and of media and other critical reagents, further reduces variability. Various classifications have been published, which define different types of in vitro cell and tissue systems (Schaeffer WI. 1990). Tissues or organ fragments can be used in a variety of systems. Ultra-thin slices of tissues, such as lung, kidney or brain, can be used to afford a preparation retaining some of the structural and functional features of the original organ.
The initial in vitro culture of collected cells taken directly from animals and humans is called primary culture. Such cultures also offer key characteristics alike to those seen in vivo, so they are usually used for basic research and in vitro applications. Although cells in some primary cultures can proliferate and can be sub cultured, they have a limited life span and they can change their characteristics with time in culture. Through recent years, translational stem cell-based research and stem cell-based clinical applications have increased. Stem cell transplanting approaches for neurological diseases comprise of embryonic stem cells and several types of adult stem cells. Most of the research has been conducted on the effects of stem cells on animal models of brain degeneration. (Vastag B. 2001). These include bone marrow-derived cells, neural stem cells and mesenchymal stem cells (Beker, 2009; Park and Eve, 2009). The clinical trials based on stem cell replacement therapy showed that the cells were able to integrate into the host brain tissue, with positive effects for the recipients and stem cells were able to restore the degenerated tissue ( Deda et al., 2009; Akesson et al., 2008). However, data from the animal models of these diseases were satisfactory and confirming the improvement of stem cell clinical applications (Orlacchio et al., 2010).
Neurological diseases have common features like neural dysfunctions, progressive deterioration and extensive loss of neural cells but splay on the grounds of pathogenic mechanism and complexity. Therefore stem cell replacement therapy should be tailored to the neural dysfunctions. Thus, stem cell treatment is confined to preclinical studies on animal models. The effectiveness of embryonic stem cells as well as of several adult stem cell types was already explored, but the most promising results were obtained by a combination of stem cells with molecules with a neurological function. (Wu et al., 2008; Sugaya and Merchant, 2008). Applications showed an improvement in the mouse’s cognitive functions and a general improvement with reference to Alzheimer’s disease pathogenesis hallmarks. This was achieved by using both neural and mesenchymal stem cell transplantation and a small molecular compound (cholinesterase inhibitor drug), leading to an improvement of mental function in animal models. For Parkinson’s disease, stem cell treatment is focused on the improvement of strategies acting on replacing degenerated neurons with other dopamine-producing cells (Villaescusa and Arenas, 2010). Michel et al., 2009, reported results on the treatment of a Parkinson’s disease patient transplanted with autologous adult neural stem/progenitor cells, signifying the long-term safety and therapeutic effects of this approach.
Neurodegenerative Diseases
Neurodegenerative diseases are neurological disorders extremely linked to brain injuries. Selective neuronal loss in certain regions of the brain causes different types of neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, stroke and many others. Two of the most common forms are Alzheimer’s disease and Parkinson’s disease and there are no cure available. Alzheimer’s disease is a lethal disorder associated with neuronal cell death beginning in hippocampus and cortex regions. Typical indications of Alzheimer’s disease are gradual memory loss, cognitive impairment and behavior dysfunction to death. The numerous pathological causes of Alzheimer’s disease in dispute, cumulative neurotoxicity induced by misfolded b- amyloid (Ab) and phosphorylated tau proteins is supported by genetic evidences (V. H. Cornejo and C. Hetz. 2013). Parkinson’s disease is a progressive neurodegenerative movement disorder linked with a selective loss of the dopamine rgic neurons and the degeneration of projecting nerve fibers in the striatum. There is no therapy clinically available that delays the neurodegenerative process. Increasing evidence suggests that oxidative stress has a main effect on the pathogenesis of Parkinson’s disease (Zecca L. et al., 2008).
