Stems cells have been recognized as a wonder drug as they provided a ray of hope to diseases where mankind had become hopeless. Thus ever since they were put to test for scientific evidence of response, more and more research has been done in the field. This has included both experimental research and clinical research. The 21st century will belong to regeneration medicine and stem cells.
This chapter aims to review the literature on the role of stem cells in various diseases with emphasis on neurologic diseases amenable to stem cell therapy. It will try to describe the mechanism of action where there is enough evidence to support it. The ethical concerns will also be discussed with insights into the future of stem cell treatment.
KeywordsAlzheimer disease, Ethics, Neurologic problems, Parkinson disease, Research, Stem cells
Hypothesis of Stem Cell Research 907
Stem Cell 907
Historical Background 908
Types of Stem Cells 908
Sources of Stem Cells 908
Mesenchymal Stem Cells 909
Stem Cells in Neurological Diseases 909
Mode of Action of Stem Cell Therapy 910
Ethical Issues 910
Recent Advances 911
Stems cells have been recognized as a wonder drug as they provided a ray of hope to diseases where mankind had become hopeless. Thus ever since they were put to test for scientific evidence of response, more and more research has been done in the field. This has included both experimental research and clinical research. The 21st century belongs to regeneration medicine and stem cells.
This chapter aims to review the literature on the role of stem cells in various diseases with emphasis on neurologic diseases amenable to stem cell therapy (SCT). It will try to describe the mechanism of action where there is enough evidence to support it. The ethical concerns will also be discussed with insights into the future of stem cell treatment.
Hypothesis of Stem Cell Research
Stem cells have been seen as agents that may help to make new cells or repair cells lost in many diseases that are caused by loss of functioning cells. SCT is thus a variety of cell-based therapy also referred to as regenerative or reparative medicine. In future, stem cells may become the basis for treating diseases such as Parkinson disease, diabetes, and heart disease.
In 1981, mouse embryonic stem cells were grown in the laboratory. However, it was later in 1998 that James Thomson isolated cells from the blastocyst at the University of Wisconsin–Madison and thus developed the first human embryonic stem cell lines. During the same time, John Gearhart at Johns Hopkins University reported the first derivation of human embryonic germ cells from the primordial germ cells. Most of the current knowledge on embryonic stem cells has emerged from in vitro fertilization technologies and basic research on mouse embryology.
The clinical applications of SCT have been explored with interest. Active stem cell active research is going on with various animal models of clinical diseases. Autologous bone marrow stem cells have been used in various pilot studies for various disorders like cardiomyopathies, diabetes, bony disorders, biliary atresia and choledochal cyst (cirrhotic livers), spina bifida, multicystic kidney, cerebral palsy, and muscular dystrophy. In India, The All India Institute of Medical Sciences, New Delhi, has been a pioneer; with the help of a centralized stem cell facility, various specialties including cardiothoracic, ophthalmology, pediatric surgery endocrinology, surgery and orthopedics have used stem cells in more than 1000 patients now, including neonates and infants for various disorders since the past 12 years.
Types of Stem Cells
Stem cells have varied potency depending on the source that they have been acquired from. Stem cells may be classified into three basic types according to the potentiality. These include:
Totipotent stem cells : Capable of forming a completely new embryo that can develop into a new organism, e.g., a fertilized egg.
Pluripotent stem cells : Unspecialized cells with potential to develop into any cell types, e.g., embryonic stem cells.
Multipotent stem cells : Possess potential to make a few cell types in the body.
Sources of Stem Cells
Selecting the appropriate stem cell type and understanding the desired mechanism of support is the initial step in developing and translating cellular therapies to patients.
There are seven major sources of human stem cells:
Adult stem cells : These are undifferentiated cells with restricted ability to produce different cell types and to self-renew. They are multipotent. They are found among specialized or differentiated cells in a tissue or organ after birth, e.g., bone marrow, muscle, and brain.
Umbilical cord blood stem cells : They are found in the umbilical cord of newborns and are similar to adult stem cells in differentiating properties. However, their advantages include widespread availability and immaturity, which may play a significant role in reduced rejection after transplantation into a mismatched host, and their ability to produce larger quantities of homogenous tissue or cells.
Embryonic stem cells : These are collected from 5- to 6-day-old blastocysts, the inner cell mass of an early embryo. They are pluripotent. Once these cells are removed from the embryo, they can no longer give rise to a whole organism.
Germline : Embryonic germline stem cells are immature cells derived from the part of a human embryo or fetus that will ultimately produce sperm and egg cells (gametes). They are pluripotent.
Fetal stem cells : There are collected from the fetus in various stages of development.
Amniotic fluid stem cells : They have the potential to differentiate into cells of all three embryonic germ layers. They have low immunogenicity and antiinflammatory functions.
Placental stem cells : Cells derived from the placenta have phenotypic plasticity and the immunomodulatory properties. Recently, chorionic mesenchymal stem cells (MSCs) have been found to possess superior differentiation, immunosuppressive, and angiogenic potentials in comparison with haploidentical maternal placental cells.
Mesenchymal Stem Cells
MSCs are a group of clonogenic cells present among the bone marrow stroma and capable of multilineage differentiation into mesoderm-type cells such as osteoblasts, adipocytes, and chondrocytes. Due to their ease of isolation and their differentiation potential, MSCs are being introduced into clinical medicine in a variety of applications and through different ways of administration. MSCs are preferentially home to damaged tissue and thus may have therapeutic potential. In vitro data suggest that MSCs have low inherent immunogenicity as they induce little, if any, proliferation of allergenic lymphocytes. Instead, MSCs appear to be immunosuppressive in vitro. They inhibit T-cell proliferation to alloantigens and mitogens and prevent the development of cytotoxic T-cells. MSCs can be derived from adult bone marrow and can transdifferentiate to a neural lineage.
Stem Cells in Neurological Diseases
Currently, there is substantial evidence that stem cells can act as a support environment for survival or recovery of damaged neurons by reducing inflammation and helping remyelination. Hypoxic, traumatic, infective, or degenerative lesions may be benefitted with ongoing research in stem cell applications. Neurodegenerative disorders like Parkinson disease, Alzheimer disease, Huntington disease, multiple sclerosis, spinal muscular atrophy, and amyotrophic lateral sclerosis may be halted or slowed in progression by the use of stem cells.
Stem cells produce neurotrophic or immunosuppressive factors thus forming a favorable environment for neuronal tissue repair. Neurons and glial cells have been successfully developed from stem cells. An ideal fully functional neuron cell derived from a stem cell should be electrically excitable, release the appropriate neurotransmitter, and form neural structures like processes and synapses to offer therapeutic benefit for neurological diseases. Neural stem cells can be derived directly from fetal or adult neural tissue or by differentiation of embryonic stem cells via cell culture manipulation. Induced pluripotent stem cells have been generated from autologous tissues like fibroblasts and reprogrammed into embryonic stem–like cells by the addition of transcription factors. In children, SCT has been tried in meningomyelocele, cerebral palsy, perinatal brain injury, neurogenic bowel and neurogenic bladder ( Table 57.1 ).
|5.||Amyotrophic lateral sclerosis|
|8.||Spinal cord injury|
|10.||Spinal muscular atrophy|
|11.||Neurological deficits in meningomyelocele|
|12.||Duchenne muscular dystrophy|