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From the beginning of time, humanity has relied on ancient medicinal beliefs to sustain the human race. Bloodletting and trepanation were irrational therapies that persisted for thousands of years at a time, but now things are very different. Whether it be new diagnostics for early and accurate identification of diseases or modern day targeted drug therapies to mitigate the debilitating symptoms of infection, healthcare has grown drastically. Along with advancements in oncology, prosthetic limbs, and potential cures to HIV in the past decade, stem cell research has been an integral part of recent emerging medicine.
Stem cells are cells that can develop into a multitude of other specified cell types through a process known as differentiation. In terms of development, embryonic stem cells are initially present to aid in the morphogenesis of distinct organs from a single zygote. However, undifferentiated adult stem cells still remain throughout the body during aging. Most stem cells are targeted to a certain group of cells within the body, but the remarkable capabilities of these cells have nearly endless applications in treating disease. Harnessing the potential of stem cells would allow us to replace damaged cells or release biochemicals in diseased patients. Current research has exploited uses in degenerative disorders such as osteoarthritis or even the neurological degradation present in Parkinson’s disease and Alzheimer’s disease. Other revolutionary applications include the treatment of heart disease, diabetes, strokes, and even macular degeneration. A research group at the Duke University Medical Center showed a 70% behavioral improvement rate by the transplant of umbilical blood derived stem cells into autistic children, thus showing viable treatment options for the Autism Spectrum Disorder. Meanwhile, researchers at Lehigh University continue to study the uses of neural stem cells to regulate neurotransmitter levels in psychiatric disorders such as Schizophrenia.
However, while considering the enormous benefits of stem cell research on the medical community, many questions and controversy remains uncertain in the field.
With the initial rise of the concept of stem cells, debate arose over the need to harvest human embryonic stem cells. This method consisted of the usage of living human embryos from donors, however bioethical advocates expressed concern regarding the respect for human life. This brought up much controversy within the scientific community between two moral principles: a responsibility to protect human life versus a compulsion to preserve existing life from disease and suffering.
Due to such ethical anxiety, much of the exfoliation of stem cell therapy had been initially stunted until the discovery of induced Pluripotent Stem Cells (iPSCs). These artificially created stem cells were first discovered by Japanese researcher, Shinya Yamanaka, in 2006 and who later went on to win the 2012 Nobel Prize in Physiology and Medicine. Growth of iPSCs is initiated though deriving cells from an adult organism (originally skin fibroblasts of a mouse) and manipulating only four genes in order to retrograde that cell back to a stem cell. This technique makes science fiction like cloning and growing organs very possible in the near future. The new developments in CRISPR–Cas9 also may enhance current methods of induced Pluripotent Stem Cell derivation, using the novel genome editing technology to target particular genes with more accuracy. CRISPR can allow scientists to embed mutations into iPSCs to model diseases and drug therapy on a cellular level. Due to the mimicry of iPSCs to embryonic stem cells during fetal development, researchers continue to look towards the evolution of the Zika virus in pregnant women, and its correlation with microcephaly. IPSCs may be the future of understanding aging and potentially being a rewind button on biological time. If scientists can develop artificial embryonic stem cells from adult fully developed cells, then the same principle may show evident on the full scale for reversing time for all cells through a simple manipulation of four genes. Though iPSCs have resolved the heated stem cell controversy, they have provided geneticists much more insight into the potential of stem cells.
Another type of stem cell particularly shows much promise in pharmaceutical research and regenerative medicine. Mesenchymal stem cells are multipotent stem cells of the stromal connective tissue, which can differentiate into myocytes, chondrocytes, osteoblasts, and adipocytes. Utilizing extracellular drugs to induce signaling pathways, new technologies look to manipulate the lineage of existing mesenchymal stem cells to restore lost tissue with aging and disease. For example, arthritis can be treated by targeted differentiation of chondrocytes, or cartilage cells. In vitro differentiation could provide a source of cartilage to treat damage to cartilage throughout the body (nasal septum, bronchiole tubes, etc.). The same principle can apply for bone diseases such as osteoporosis and harnessing the opposite ability to slow bone cell growth in osteosarcoma. Even certain heat conditions related to weak muscle tissue such as cardiomyopathy could be suppressed by enhancing cardiomyocyte differentiation.
Other neural stem cell lines are undergoing heavy research to shed light on neurological and psychiatric disorders. Triggering the differentiation of neurons on a plate can allow for the modeling of such diseases and their interactions with variable drug molecules. Certain neurons produce specific neurotransmitters that in excess may also cause disease; immunocytochemical procedures allow biochemists to identify microtubules specific to such neurons. A molecule binding to cytoskeletal receptors to trigger the differentiation of dopaminergic neurons, or dopamine producing neural cells, would be a viable drug for Parkinson’s Disease since a lack of dopamine is associated with Parkinsonism. However, the inverse concept – a drug that suppresses dopaminergic differentiation of neural stem cells – could also treat Schizophrenia due to the overactivity of the neurochemical in patients with the disorder. Harnessing neural stem cells’ abilities to regulate neurotransmitter function may be the future of psychiatric medicine.
Considering the remarkable future of healthcare stem cell research provides, many questions still remain uncertain on the path ahead. What molecular and cellular mechanisms physically induce targeted differentiation? And how can we manipulate this? Can we develop patient specific therapies using one’s own stem cells rather than generalized medications? If we could use patients’ own cells to regenerate their organs, instead of waiting on a transplant list or to replace damaged cells due to disease, the fundamental basis of medicine would be changed forever. In spite of all the progress made, much research remains. Some potential challenges may arise regarding avoiding uncontrollable growth after enhanced growth with stem cell therapeutics. A middle ground must be established between no effect and cancerous growth of regenerated tissue after therapy to avoid initiating a tumor, perhaps worsening the initial condition.
For neurological disorders, allowing drug molecules to cross the blood brain barrier has always been a challenge. If no nanotechnology is infused, then the patient is at risk for debilitating symptoms, as the molecule will target peripheral sites. For example, dopamine agonists have severe side effects of psychosis due to the excess of dopamine in the blood stream, as opposed to the substantia nigra when targeting Parkinson’s disease.
Stem cell transplants may soon become a reality and are shedding light on new possibility in the field. It will be a long road until then but as of now, it’s incredible to watch the research process.