Stem cells: Current applications and future prospects

Potency

A zygote cell is totipotent and can develop into any of the three germ layers (mesoderm, ectoderm, and endoderm) and form the placenta. The zygote develops into the blastocyst, where the inner cell mass (later, the embryo) contains pluripotent stem cells (PSCs) which can differentiate into any of the three germ layers but not any extraembryonic structure (placenta). The trophectoderm of the blastocyst develops into the placenta, which contains PSCs.^[2] PSCs differentiate into multipotent stem cells which can differentiate into any cell of a specific lineage but converts into an oligopotent stem cell after differentiating. For example, a multipotent hematopoietic stem cell (HSC) differentiates into an oligopotent myeloid stem cell. An oligopotent stem cell can differentiate into multiple different cell types of a single lineage and an unipotent stem cell divides repeatedly into the same type of cell.^[3]

Origin

Stem cells obtained from human embryos are embryonic stem (ES) cells and those obtained from developed organs and tissues are called adult stem cells. Adult stem cells are mostly used by the body to repair and replace damaged tissue. Furthermore, cells that are harvested from the umbilical cord after childbirth are called cord blood stem cells, stem cells found in amniotic fluid are called amniotic fluid stem cells, and stem cells obtained from the placenta are called placental stem cells. Cord blood stem cells are used to treat children with blood cancers.^[4] Placental stem cells are a great source of fetal mesenchymal stem cells (MSCs).^[2]

All stem cells are surrounded by a special environment inside the body called the niche. When the niche is changed due to some external stress such as injury or transplantation into a different environment, stem cells show the property of plasticity. This means they can differentiate into a wider variety of cells required by their new surroundings. For instance, skin sweat gland stem cells, when transplanted into mammary fat pads, can form milk-producing glandular structures. Inside the body, along with nearby stem cells replenishing a vacancy, committed progeny can also dedifferentiate and assume the same role.^[5]

In addition, it is possible to convert adult stem cells into PSCs, called induced PSCs (iPSCs).^[6] They can be used as an alternative to ES cells.^[7]

HSC transplantation

Healthy HSCs can be transplanted into patients suffering from various types of bone marrow or blood disorders such as leukemia, lymphoma, and tumors to replace the dysfunctional bone marrow cells. The transfer can be autologous (cells originating from the patient), allogeneic (cells originating from a different person), or syngeneic (cells originating from identical twins).^[8] Bone marrow transplants have a long history and have become a standard medical procedure.^[9]

HSC therapy (HSCT)

HSCT has been used to treat multiple sclerosis in clinical trials. Multiple sclerosis is an autoimmune disease targeting the central nervous system. The traditional approach for the treatment of multiple sclerosis is disease-modifying therapy (DMT). DMT targets the immune system by modulating it, alternating the immune cell trafficking, or reducing the immune cell population. However, it requires long-term administration and can have serious side effects. The clinical trials of HSCT have produced better results than DMT.^[10]

Placental stem cell therapy

Placental stem cells have shown promising results and potential in healing and curing diseases in various parts of the body such as Alzheimer’s, liver diseases, pancreatic diseases, myocardial infarction, muscle dystrophy, lung fibrosis, and large lytic lesions in bones. They also have applications in tissue engineering.^[2]

Autologous limbal stem cells (holoclar) transplantation

Autologous limbal cell culture contains stem cells (holoclones) that can be used to treat patients with loss of corneal epithelium.^[11] Burns to the eye may lead to loss of vision by destroying the limbus or causing limbal stem cell deficiency.^[12] Holoclar has been formally approved in Europe for moderate to severe limbal stem cell deficiency in adults.^[13]

Development toward artificial organ engineering

When stem cells are cultured in a 3D environment, in permissive growth conditions without any external input, they multiply and differentiate into structures like their origin. These structures mimic organs, including providing the niche for stem cells, and are called “organoids.” Organoids show a level of organization that is not replicable with current technology, but they show heterogeneity in size, shape, cell composition, etc., from culture to culture. These organoids are used for various studies.^[14]

Hollow organ engineering

Stem cells show promising results in the engineering of hollow organs such as trachea and vagina. There is a case report showing the successful use of autologous stem cells for the successful production of trachea.^[15] Stem cells can be used to engineer new trachea for patients suffering due to mustard gas.^[16] The use of appropriate scaffold along with MSCs can form the basis for developing artificial vagina for treating many diseases which are ignored or have non-effective treatments.^[17]

Anti-aging effects

The aging process is characterized by molecular mechanisms, including DNA damage, telomere shortening, loss of proteostasis, mitochondrial dysfunction, and stem cell exhaustion.^[18] Adipose-derived stem cells promote mitophagy and increase mitochondrial production while also reducing reactive oxygen species, eventually changing the cell metabolism to resemble youthful cells. The pathways related to the metabolism of nucleotides and those associated with mitochondria are enriched as well.^[19]

Minimizing mitochondrial injury

Mitochondrial dysfunction plays an important role in the pathogenesis of many seemingly unrelated diseases such as neurodegenerative disorders, cardiac diseases, sepsis, cancer, diabetes, and fluoroquinolone-associated disability.^[20] MSCs accelerate mitochondrial recovery, promote mitophagy, and induce the transfer of healthy mitochondria in cells suffering from mitochondrial damage or dysfunction.^[21]

Treatment of diabetes

Multiple types of stem cells have been used to treat diabetes in clinical trials.^[22] Diabetes mellitus can be caused by lifestyle choices and genetic inheritance (type 2 diabetes), autoimmune causes (type 1 diabetes), or even hormonal changes due to pregnancy (gestational diabetes).^[23] Typical treatment of diabetes includes injection of insulin, but it poses an issue due to high insulin costs and the temporary nature of the treatment.^[24] Stem cells can solve this problem by directly healing the pancreatic cells. In addition, diabetes-related injuries such as non-healing wounds are being treated using stem cells.^[25]

Disease modeling and study of differentiation

Since their development, iPSCs have been used by scientists in a variety of ways for studying the pathogenesis of diseases, for inventing novel ways of iPSC formation, for studying the inheritance of genetic diseases, for studying neurodegenerative diseases, etc.^[7]

Cell-free therapy

Cell-derived membrane-bound vesicles and extracellular vesicles (EVs) from stem cells such as exosomes have been shown to have effects such as neuroprotection, neuroregeneration, neural development, and improvement in neural function. The use of EVs reduces the risks and limitations of cell-based therapy, being non-invasive, crossing blood–brain barrier, and being non-tumorous.^[26]

Wound healing

Stem cells promote cell proliferation and cell differentiation at the wound site, help in the control of immune response, and contain antibacterial properties due to the secretion of antimicrobial factors. The use of autologous stem cells removes the possibility of immune rejection.^[27]

Treatment of burn wounds

Stem cells show better potential and results in treating burn wounds than currently available methods. Using stem cells by direct injection, tissue-engineered grafts or exosome treatment shows promising results in burn wound healing.^[28]

Significance in research

Stem cells are being used to study diseases such as congenital heart disease, and neurodevelopmental defects and for the study of the effects of the environment on cell and tissue development.^[29]

Stem cells in gene editing

By combining stem cell technology with gene editing methods like CRISPR-Cas9, new opportunities for treating hereditary disorders and fixing genetic flaws are made possible. Gene-edited stem cells may be used to treat genetic diseases and lessen the chance of damaging mutations being passed onto future generations.

Stem cells for autoimmune illnesses

The immune deficiencies suffered due to AIDS can be treated using stem cells.^[34] They control the immune system and encourage tissue regeneration, holding potential for treating autoimmune illnesses. Future studies will concentrate on creating secure and efficient stem cell treatments for diseases such as type 1 diabetes, rheumatoid arthritis, and multiple sclerosis.

Regenerative medicine

In the field of regenerative medicine, damaged or diseased tissues and organs can be repaired or replaced with healthy cells derived from stem cells. This could revolutionize the treatment of conditions such as heart disease, Parkinson’s, spinal cord injuries, and more.

Personalized medicine

With the advent of iPSCs, it is now possible to derive stem cells from a patient’s cells, creating an unlimited source of personalized cells for therapeutic use. IPSCs can be genetically matched to the patient, significantly reducing the risk of immune rejection, and enabling tailored treatments for various medical conditions.

Tissue engineering

Organoids can be used for drug testing, disease modeling, and personalized medicine, paving the way for more precise and efficient treatments.

Artificial organs and body parts

In the not-so-distant future, we might witness the creation of fully functional artificial organs and body parts using stem cells. This could potentially alleviate the organ shortage for transplants and provide customized solutions for patients in need.