Published On: 16th March, 2024
ABSTRACT
In recent years, stem cell therapy has become a pinnacle of all research in the field of irreversible and incurable diseases like diabetes, heart disease, spinal cord injuries, Parkinson’s, and Alzheimer’s disease. Stem cells can be divided into two broad categories – Embryonic stem cells and adult stem cells.
In this article, we outline the significance and applications of these stem cells trying to understand the potential they carry using past and ongoing research in the field. We conclude by discussing the impact of stem cell therapy in the long run and the potential obstacles while also enunciating the ethical issues that arise during research.
KEYWORDS – Stem cells, pluripotent stem cells, embryonic stem cells,
INTRODUCTION – DEFINING STEM CELLS AND UNDERSTANDING THEIR SIGNIFICANCE
Over the years, scientists and researchers have comprehensively contributed towards creating an understanding of the living systems and the human body. There is no better place to begin this analysis than by studying the cells that give rise to all life—THE STEM CELLS.
This raises many questions in our mind like- What are stem cells? What is their purpose? How do they function? Where are these cells situated in the body? Can these cells be used to treat several terminal diseases and improve the quality of human life? and a ton more.
Stem cells are undifferentiated cells that have the potential to form any kind of cell during embryonic growth or tissue repair in adults. The ability of stem cells to self-renew is remarkable.
These cells divide symmetrically to give rise to two identical daughters stem cells and asymmetrically to form one differentiating cell and one daughter stem cell.
Figure – Cell divisions in stem cells [1]
These cells are broadly divided into two categories:
- Embryonic Stem Cells –
Embryonic stem cells are undifferentiated cells of an embryo that can form any type of cell (called pluripotent) of the adult body.
They can be found inside the human blastocyst’s inner cell mass. This is a stage of embryo development that lasts between the 4th and 7th day following fertilization. These cells typically disappear after the 7th day and proceed to form the three embryonic tissue layers. However, if ESCs are extracted from the inner cell mass during the blastocyst phase, they can be cultured in a laboratory and will continue to proliferate indefinitely under the right conditions. [2]
ESCs have shown remarkable results in the field of regenerative medicine.
- Adult/Somatic Stem Cells –
Adult stem cells transform into specific cell types that are found in the organ or tissue they inhabit; these cells may display distinct physical characteristics and gene expression patterns that are representative of that tissue. Adult stem cells, unlike the ESCs, which can become any part of the body, have been found in a wide range of tissues including skin, heart, brain, liver, and bone marrow usually restricted to become any type of cell in that particular tissue (called multipotent).
These stem cells can stay dormant and not divide for extended periods. They become active when the body requires more cells to heal or maintain tissues.
Types of Adult Stem Cells –
- Hematopoietic Stem Cells (Blood Stem Cells)
- Mesenchymal Stem Cells
- Neural Stem Cells
- Epithelial Stem Cells
- Skin Stem Cells
PLURIPOTENT STEM CELLS: These are cells that possess the ability to form any kind of cells or tissue in the organism and as Pluripotent stem cells can differentiate into any cell type, it enables scientists to study human development and disease in vitro.
Different types of pluripotent cells under research: [3]
- iPS cells – typically made from skin or blood cells by a process called ‘reprogramming’.
- ES cells – typically derived from leftover embryos donated after IVF
- ntES cells – generated from embryos after replacing an egg’s nucleus with that of an adult cell.
- pES cells – obtained from embryos produced by an unfertilized
Figure[4] – Culturing pluripotent cells
MAIN (Body)
HISTORY OF STEM CELL RESEARCH –
In the early 1960s, Sir John Gurdon discovered that cells could be reverted to a more primitive state with greater
developmental potential, contrary to the prevalent belief at that time. He demonstrated this by injecting the nucleus of a differentiated frog cell into an egg cell, which had its nucleus removed. When the egg was allowed to develop, it gave rise to a fertile adult frog, which proved that differentiated cells retain the information required to create all cell types in the body.
Martin Evans (Nobel Prize, 2007) and Matt Kauffman were the first to identify, isolate, and successfully culture ES cells using mouse blastocysts in 1981.
The turning point in stem cell research was in 2006 when Shinya Yamanaka and Kazutoshi Takahashi discovered that multipotent stem cells could be cultured into pluripotent stem cells (also called iPSC). This led to a new era in the field of stem cell therapy as it gave a much wider perspective on the significance and ways to utilize embryonic stem cells as regenerative medicine.
Periodically arranged milestones in stem cell research can be seen in the figure below:
Figure – Time axis for 25 major discoveries in stem cell research [4]
APPLICATIONS OF STEM CELL THERAPY BEING USED IN THE PRESENT
According to a research paper in 2016 [5], organ or tissue transplant for the functional restoration of severely damaged organs of patients suffering from chronic diseases is not conventional for various reasons like the body’s inability to generate regenerative responses due to old age, hence as a substitute stem cell therapy as a regenerative medicine has emerged rapidly.
From a therapeutic point of view, stem cells can be categorized into 6 classes having multiple specific regenerative potentials –
- ESCs –
- Improvement of spinal cord injury
- Regeneration of retinal sheet
- Generation of retinal ganglion cells
- Healing of heart defects
- Hepatic cell formation
- Formation of insulin-secreting B-cells
- Cartilage lesion treatment
- Regeneration of pacemaker
- In vitro gametogenesis
- TSPSCs –
- Treatment of diabetes and retinopathy
- Neurocentral therapeutic applications
- Restoration of cognitive functions
- Brain and cancer treatment
- Ear acoustic function restoration
- Regeneration of intestinal mucosa
- Treatment of vision defects
- Muscle regeneration
- Regeneration of fallopian tube
- MSCs –
- Regeneration of bladder tissue
- Muscle regeneration
- Regeneration of teeth tissue
- Healing of orthopedic injuries
- Recovery from muscle injuries
- Hear scar repair after attack
- UCSCs –
- TIDM and T2DM treatment
- SLE (autoimmune disease) treatment
- Application for HI treatment
- Krabbe’s disease treatment
- Haematopoiesis in neuroblastoma
- BMSCs –
- Treatment of anemia and blood cancer
- Retroviral therapy
- Correction of neuronal defects
- Generation of functional platelets
- Alveolar bone regeneration
- Regeneration of diaphragm tissue
- iPSCs
- Regeneration of kidney tissue
- Vision restoration in AMD
- Treatment of placental defects
- Treatment of brain cortex defects
- ASD and autism treatment
- Treatment of liver and lung disease
- Generation of serotonin neurons
- Regeneration of pacemaker
Figure – Diseases treated and therapies in clinical trials with stem cells [6]
FUTURE OF STEM CELL THERAPY AND ETHICAL ISSUES
Stem cells require extensive research before their usage can be extended. To control the type of cells created from embryonic stem cells, scientists must comprehend how these cells develop. However, several challenges need to be overcome. First, the embryonic stem cells that are currently available are likely to be rejected by the body. Second, some people are ethically opposed to using stem cells that come from embryos.
Researchers also face several challenges while working with adult pluripotent stem cells. These cells are difficult to cultivate in a laboratory environment, hence scientists are exploring methods to enhance the process. Additionally, these cells are present in minimal quantities in the body, thus increasing the likelihood of having DNA-related issues.
From a completely scientific viewpoint stem cell research is still a very intriguing genre with lots of promise for success in innovating cures for serious and deadly diseases in the future due to the clinical trials going on continuously. But moral questions that emerge from the use of embryos (which even introduces the risk of reproductive cloning) cannot be neglected and therefore limit the conditions of this research
Along with this, there are also questions raised on the medical efficacy and safety of these procedures as well as maintaining the anonymity of the donor, if asked by the patient. From another perspective, an economic parity would be seen in patients having access to these new procedures.
To monitor these concerns the Indian Council for Medical Research had set guidelines for biomedical research on human subjects in 2000 that always need to be abided by when conducting research and clinical trials. The ICMR has also established a separate National Apex Committee (NAC) for Stem Cell Research and Therapy.
The International Society for Stem Cell Research
In the early 21st century, scientists discovered the technology to create human embryonic stem cells. However, there was a debate among several countries on how to regulate the use of these cells. Stem cell scientists also discussed these questions but there was no organized international forum where they could exchange ideas, share research results, and discuss the ethical implications of stem cells and their use in developing therapies. As a result, the International Society for Stem Cell
Research (ISSCR) was established to serve as an organized international platform for exchanging ideas, showcasing the latest research results, and discussing the ethical implications of stem cells and their use in future therapy development.
Figure – Time axis for ISSCR milestones [4]
CONCLUSION and DISCUSSION
Stem cell research has shown very promising results and expanded our knowledge in the field of regenerative medicine and tackling deadly diseases. We discussed various applications of different types of stem cells, with recent and upcoming clinical trials this knowledge will only enhance and open more locks in this genre
We also discussed the future aspects and ethical issues that arise during stem cell research, a most intriguing question is whether is it rational to artificially increase the longevity of one’s life using complete cell transfer therapies. While these concerns and issues are completely valid, the research should not be hindered as it allows us to develop more and more even in the allied topics other than stem cell therapy.
ABBREVIATION
- ESC – Embryonic stem cells
- iPS cells – Induced pluripotent stem cells
- ES cells – Conventional embryonic stem cells
- ntES cells – Nuclear transfer ES cells
- pES cells – Parthenogenetic ES cells
- TSPSCs – Tissue specific progenitor stem cells
- UCSCs – Umbilical cord stem cells
- BMSCs – Bone marrow stem cells
- iPSCs – Induced pluripotent stem cells
- MSCs – Mesenchymal stem cells
REFERENCES
[1] https://www.researchgate.net/figure/Symmetric-versus-asymmetric-cell-division- Symmetric-cell-division-occurs-when-a-stem_fig1_348888936
[2] National Research Council (US) and Institute of Medicine (US) Committee on the
Biological and Biomedical Applications of Stem Cell Research. Stem Cells and the Future of Regenerative Medicine. Washington (DC): National Academies Press (US); 2002. CHAPTER THREE, Embryonic Stem Cells. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK223690/
[3] https://www.childrenshospital.org/research/programs/stem-cell-program- research/stem-cell-research/pluripotent-stem-cell-research
[4] Urban Lendahl (2022, 14 June) 100 plus years of stem cell research—20 years of ISSCR, Department of Cell and Molecular Biology, Karolinska Institute, 17177 Stockholm, Sweden https://www.sciencedirect.com/science/article/pii/S221367112200193X#sec1
[5] Mahla RS. (2016) Stem Cells Applications in Regenerative Medicine and Disease Int J Cell Biol. 2016; 2016:6940283. doi: 10.1155/2016/6940283. Epub 2016 Jul 19. PMID: 27516776; PMCID: PMC4969512.
[5] Zakrzewski, W., Dobrzyński, M., Szymonowicz, M. et al. (2019) Stem cells: past, present, and Stem Cell Res Ther 10, 68. https://doi.org/10.1186/s13287-019-1165-5
[6] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105090/figure/fig1/