Scientists are already using stem cells in the laboratory to screen new drugs and to develop model systems to study normal growth and identify the causes of birth defects. Research on stem cells continues to advance knowledge about how an organism develops from a single cell and how healthy cells replace damaged cells in adult organisms. Stem cell research is one of the most fascinating areas of contemporary biology, but, as with many expanding fields of scientific inquiry, research on stem cells raises scientific questions as rapidly as it generates new discoveries.
Some stem cells, such as the adult bone marrow or peripheral blood stem cells, have been used in clinical therapies for over 40 years. Other therapies utilizing stem cells include skin replacement from adult stem cells harvested from hair follicles that have been grown in culture to produce skin grafts.
In IVF clinics, the doctors fertilize several eggs in a test tube, to ensure that at least one survives.
They will then implant a limited number of eggs to start a pregnancy. This single-celled zygote then starts to divide, forming 2, 4, 8, 16 cells, and so on. Now it is an embryo. Soon, and before the embryo implants in the uterus, this mass of around — cells is the blastocyst. The blastocyst consists of two parts:. The inner cell mass is where embryonic stem cells are found. Scientists call these totipotent cells. The term totipotent refer to the fact that they have total potential to develop into any cell in the body.
With the right stimulation, the cells can become blood cells, skin cells, and all the other cell types that a body needs. In early pregnancy, the blastocyst stage continues for about 5 days before the embryo implants in the uterus, or womb. At this stage, stem cells begin to differentiate. Scientists have used MSCs to create new body tissues, such as bone, cartilage, and fat cells. They may one day play a role in solving a wide range of health problems.
Scientists create these in a lab, using skin cells and other tissue-specific cells. These cells behave in a similar way to embryonic stem cells, so they could be useful for developing a range of therapies. To grow stem cells, scientists first extract samples from adult tissue or an embryo. They then place these cells in a controlled culture where they will divide and reproduce but not specialize further. Stem cells that are dividing and reproducing in a controlled culture are called a stem-cell line.
Researchers manage and share stem-cell lines for different purposes. They can stimulate the stem cells to specialize in a particular way. This process is known as directed differentiation.
Until now, it has been easier to grow large numbers of embryonic stem cells than adult stem cells. However, scientists are making progress with both cell types. Researchers categorize stem cells, according to their potential to differentiate into other types of cells. Embryonic stem cells are the most potent, as their job is to become every type of cell in the body. Totipotent : These stem cells can differentiate into all possible cell types.
The first few cells that appear as the zygote starts to divide are totipotent. Pluripotent : These cells can turn into almost any cell. Cells from the early embryo are pluripotent.
Multipotent : These cells can differentiate into a closely related family of cells. Adult hematopoietic stem cells, for example, can become red and white blood cells or platelets. Oligopotent : These can differentiate into a few different cell types. Adult lymphoid or myeloid stem cells can do this. Unipotent : These can only produce cells of one kind, which is their own type. In some cases, they can also fix damaged tissues. Researchers believe that stem cell-based therapies may one day be used to treat serious illnesses such as paralysis and Alzheimer disease.
Embryonic stem cells. The embryonic stem cells used in research today come from unused embryos. These result from an in vitro fertilization procedure. They are donated to science. These embryonic stem cells are pluripotent.
This means that they can turn into more than one type of cell. Adult stem cells. There are 2 types of adult stem cells. One type comes from fully developed tissues such as the brain, skin, and bone marrow.
Their procedure revealed that these genes can also be used for effective regenerative treatment [ 97 ]. The main challenge of their method was the need to employ an approach that does not use transgenic animals and does not require an indefinitely long application. The first clinical approach would be preventive, focused on stopping or slowing the ageing rate.
Later, progressive rejuvenation of old individuals can be attempted. In the future, this method may raise some ethical issues, such as overpopulation, leading to lower availability of food and energy. For now, it is important to learn how to implement cell reprogramming technology in non-transgenic elder animals and humans to erase marks of ageing without removing the epigenetic marks of cell identity.
Stem cells can be induced to become a specific cell type that is required to repair damaged or destroyed tissues Fig. Currently, when the need for transplantable tissues and organs outweighs the possible supply, stem cells appear to be a perfect solution for the problem. The most common conditions that benefit from such therapy are macular degenerations [ 98 ], strokes [ 99 ], osteoarthritis [ 89 , 90 ], neurodegenerative diseases, and diabetes [ ].
Due to this technique, it can become possible to generate healthy heart muscle cells and later transplant them to patients with heart disease. Stem cell experiments on animals. These experiments are one of the many procedures that proved stem cells to be a crucial factor in future regenerative medicine.
In the case of type 1 diabetes, insulin-producing cells in the pancreas are destroyed due to an autoimmunological reaction. As an alternative to transplantation therapy, it can be possible to induce stem cells to differentiate into insulin-producing cells [ ].
They can be stored in a tissue bank to be an essential source of human tissue used for medical examination. The problem with conventional differentiated tissue cells held in the laboratory is that their propagation features diminish after time. This does not occur in iPSCs. The umbilical cord is known to be rich in mesenchymal stem cells.
Due to its cryopreservation immediately after birth, its stem cells can be successfully stored and used in therapies to prevent the future life-threatening diseases of a given patient. Stem cells of human exfoliated deciduous teeth SHED found in exfoliated deciduous teeth has the ability to develop into more types of body tissues than other stem cells [ ] Table 1. Techniques of their collection, isolation, and storage are simple and non-invasive.
Among the advantages of banking, SHED cells are:. Guaranteed donor-match autologous transplant that causes no immune reaction and rejection of cells [ ]. Not subject to the same ethical concerns as embryonic stem cells [ ]. In contrast to cord blood stem cells, SHED cells are able to regenerate into solid tissues such as connective, neural, dental, or bone tissue [ , ]. In , two researchers, Katsuhiko Hayashi et al. They succeeded in delivering healthy and fertile pups in infertile mice.
The experiment was also successful for female mice, where iPSCs formed fully functional eggs. Young adults at risk of losing their spermatogonial stem cells SSC , mostly cancer patients, are the main target group that can benefit from testicular tissue cryopreservation and autotransplantation. Effective freezing methods for adult and pre-pubertal testicular tissue are available [ ].
Qiuwan et al. For now, reaching successful infertility treatments in humans appears to be only a matter of time, but there are several challenges to overcome. First, the process needs to have high efficiency; second, the chances of forming tumours instead of eggs or sperm must be maximally reduced. The last barrier is how to mature human sperm and eggs in the lab without transplanting them to in vivo conditions, which could cause either a tumour risk or an invasive procedure.
In neuroscience, the discovery of neural stem cells NSCs has nullified the previous idea that adult CNS were not capable of neurogenesis [ , ]. Neural stem cells are capable of improving cognitive function in preclinical rodent models of AD [ , , ]. Awe et al. PD is an ideal disease for iPSC-based cell therapy [ ]. Although the results were not uniform, they showed that therapies with pure stem cells are an important and achievable therapy.
Teeth represent a very challenging material for regenerative medicine. They are difficult to recreate because of their function in aspects such as articulation, mastication, or aesthetics due to their complicated structure.
Currently, there is a chance for stem cells to become more widely used than synthetic materials. Teeth have a large advantage of being the most natural and non-invasive source of stem cells.
For now, without the use of stem cells, the most common periodontological treatments are either growth factors, grafts, or surgery. For example, there are stem cells in periodontal ligament [ , ], which are capable of differentiating into osteoblasts or cementoblasts, and their functions were also assessed in neural cells [ ]. Tissue engineering is a successful method for treating periodontal diseases. Stem cells of the root apical areas are able to recreate periodontal ligament.
One of the possible methods of tissue engineering in periodontology is gene therapy performed using adenoviruses-containing growth factors [ ]. As a result of animal studies, dentin regeneration is an effective process that results in the formation of dentin bridges [ ].
Enamel is more difficult to regenerate than dentin. After the differentiation of ameloblastoma cells into the enamel, the former is destroyed, and reparation is impossible. Medical studies have succeeded in differentiating bone marrow stem cells into ameloblastoma [ ].
Healthy dental tissue has a high amount of regular stem cells, although this number is reduced when tissue is either traumatized or inflamed [ ].
There are several dental stem cell groups that can be isolated Fig. Localization of stem cells in dental tissues. Periodontal ligaments stem cells are located in the periodontal ligament. Apical papilla consists of stem cells from the apical papilla SCAP. These were the first dental stem cells isolated from the human dental pulp, which were [ ] located inside dental pulp Table 2. They have osteogenic and chondrogenic potential. Mesenchymal stem cells MSCs of the dental pulp, when isolated, appear highly clonogenic; they can be isolated from adult tissue e.
MSCs differentiate into odontoblast-like cells and osteoblasts to form dentin and bone. Their best source locations are the third molars [ ]. DPSCs are the most useful dental source of tissue engineering due to their easy surgical accessibility, cryopreservation possibility, increased production of dentin tissues compared to non-dental stem cells, and their anti-inflammatory abilities.
These cells have the potential to be a source for maxillofacial and orthopaedic reconstructions or reconstructions even beyond the oral cavity.
DPSCs are able to generate all structures of the developed tooth [ ]. In particular, beneficial results in the use of DPSCs may be achieved when combined with other new therapies, such as periodontal tissue photobiomodulation laser stimulation , which is an efficient technique in the stimulation of proliferation and differentiation into distinct cell types [ ].
DPSCs can be induced to form neural cells to help treat neurological deficits. Stem cells of human exfoliated deciduous teeth SHED have a faster rate of proliferation than DPSCs and differentiate into an even greater number of cells, e. SHED do not undergo the same ethical concerns as embryonic stem cells.
DPSCs alone were tested and successfully applied for alveolar bone and mandible reconstruction [ ]. These cells are used in periodontal ligament or cementum tissue regeneration. PDLSCs exist both on the root and alveolar bone surfaces; however, on the latter, these cells have better differentiation abilities than on the former [ ]. PDLSCs have become the first treatment for periodontal regeneration therapy because of their safety and efficiency [ , ]. These cells are mesenchymal structures located within immature roots.
They are isolated from human immature permanent apical papilla. SCAP are the source of odontoblasts and cause apexogenesis. These stem cells can be induced in vitro to form odontoblast-like cells, neuron-like cells, or adipocytes. These cells are loose connective tissues surrounding the developing tooth germ. DFCs contain cells that can differentiate into cementoblasts, osteoblasts, and periodontal ligament cells [ , ]. Additionally, these cells proliferate after even more than 30 passages [ ].
DFCs are most commonly extracted from the sac of a third molar. When DFCs are combined with a treated dentin matrix, they can form a root-like tissue with a pulp-dentin complex and eventually form tooth roots [ ]. Dental pulp stem cells can differentiate into odontoblasts. There are few methods that enable the regeneration of the pulp.
The first is an ex vivo method. Proper stem cells are grown on a scaffold before they are implanted into the root channel [ ]. The second is an in vivo method. This method focuses on injecting stem cells into disinfected root channels after the opening of the in vivo apex. Additionally, the use of a scaffold is necessary to prevent the movement of cells towards other tissues.
For now, only pulp-like structures have been created successfully. Methods of placing stem cells into the root channel constitute are either soft scaffolding [ ] or the application of stem cells in apexogenesis or apexification. Immature teeth are the best source [ ]. Nerve and blood vessel network regeneration are extremely vital to keep pulp tissue healthy.
The potential of dental stem cells is mainly regarding the regeneration of damaged dentin and pulp or the repair of any perforations; in the future, it appears to be even possible to generate the whole tooth. Such an immense success would lead to the gradual replacement of implant treatments. Mandibulary and maxillary defects can be one of the most complicated dental problems for stem cells to address. In , it was reported that it is possible to grow teeth from stem cells obtained extra-orally, e.
Pluripotent stem cells derived from human urine were induced and generated tooth-like structures. The physical properties of the structures were similar to natural ones except for hardness [ ]. Nonetheless, it appears to be a very promising technique because it is non-invasive and relatively low-cost, and somatic cells can be used instead of embryonic cells.
More importantly, stem cells derived from urine did not form any tumours, and the use of autologous cells reduces the chances of rejection [ ]. Over recent years, graphene and its derivatives have been increasingly used as scaffold materials to mediate stem cell growth and differentiation [ ].
Both graphene and graphene oxide GO represent high in-plane stiffness [ ]. Because graphene has carbon and aromatic network, it works either covalently or non-covalently with biomolecules; in addition to its superior mechanical properties, graphene offers versatile chemistry. Graphene exhibits biocompatibility with cells and their proper adhesion. It also tested positively for enhancing the proliferation or differentiation of stem cells [ ].
After positive experiments, graphene revealed great potential as a scaffold and guide for specific lineages of stem cell differentiation [ ]. Graphene has been successfully used in the transplantation of hMSCs and their guided differentiation to specific cells. The acceleration skills of graphene differentiation and division were also investigated. It was discovered that graphene can serve as a platform with increased adhesion for both growth factors and differentiation chemicals.
Extracellular vesicles EVs can be released by virtually every cell of an organism, including stem cells [ ], and are involved in intercellular communication through the delivery of their mRNAs, lipids, and proteins. As Oh et al. IncRNAs can bind to specific loci and create epigenetic regulators, which leads to the formation of epigenetic modifications in recipient cells.
Because of this feature, exosomes are believed to be implicated in cell-to-cell communication and the progression of diseases such as cancer [ ]. Recently, many studies have also shown the therapeutic use of exosomes derived from stem cells, e.
In intrinsic skin ageing, on the other hand, the loss of elasticity is a characteristic feature. The skin dermis consists of fibroblasts, which are responsible for the synthesis of crucial skin elements, such as procollagen or elastic fibres.
These elements form either basic framework extracellular matrix constituents of the skin dermis or play a major role in tissue elasticity. Fibroblast efficiency and abundance decrease with ageing [ ].
Huh et al. It was discovered that, in addition to the induction of fibroblast physiology, hAFSC transplantation also improved diseases in cases of renal pathology, various cancers, or stroke [ , ]. Oh [ ] also presented another option for the treatment of skin wounds, either caused by physical damage or due to diabetic ulcers.
Induced pluripotent stem cell-conditioned medium iPSC-CM without any animal-derived components induced dermal fibroblast proliferation and migration.
During the crucial step of proliferation, fibroblasts migrate and increase in number, indicating that it is a critical step in skin repair, and factors such as iPSC-CM that impact it can improve the whole cutaneous wound healing process.
Paracrine actions performed by iPSCs are also important for this therapeutic effect [ ]. Bae et al. It was also demonstrated that iPSC factors can enhance skin wound healing in vivo and in vitro when Zhou et al. Peng et al. However, the research article points out that the procedure was accomplished only on in vitro acquired retina. Although stem cells appear to be an ideal solution for medicine, there are still many obstacles that need to be overcome in the future.
One of the first problems is ethical concern. The most common pluripotent stem cells are ESCs. Therapies concerning their use at the beginning were, and still are, the source of ethical conflicts.
The reason behind it started when, in , scientists discovered the possibility of removing ESCs from human embryos. Stem cell therapy appeared to be very effective in treating many, even previously incurable, diseases.
The problem was that when scientists isolated ESCs in the lab, the embryo, which had potential for becoming a human, was destroyed Fig. Because of this, scientists, seeing a large potential in this treatment method, focused their efforts on making it possible to isolate stem cells without endangering their source—the embryo.
Use of inner cell mass pluripotent stem cells and their stimulation to differentiate into desired cell types.
For now, while hESCs still remain an ethically debatable source of cells, they are potentially powerful tools to be used for therapeutic applications of tissue regeneration. Because of the complexity of stem cell control systems, there is still much to be learned through observations in vitro.
For stem cells to become a popular and widely accessible procedure, tumour risk must be assessed. New cells need to have the ability to fully replace lost or malfunctioning natural cells. Additionally, there is a concern about the possibility of obtaining stem cells without the risk of morbidity or pain for either the patient or the donor. Uncontrolled proliferation and differentiation of cells after implementation must also be assessed before its use in a wide variety of regenerative procedures on living patients [ ].
One of the arguments that limit the use of iPSCs is their infamous role in tumourigenicity. There is a risk that the expression of oncogenes may increase when cells are being reprogrammed. In , a technique was discovered that allowed scientists to remove oncogenes after a cell achieved pluripotency, although it is not efficient yet and takes a longer amount of time. The process of reprogramming may be enhanced by deletion of the tumour suppressor gene p53, but this gene also acts as a key regulator of cancer, which makes it impossible to remove in order to avoid more mutations in the reprogrammed cell.
The low efficiency of the process is another problem, which is progressively becoming reduced with each year. The use of transcription factors creates a risk of genomic insertion and further mutation of the target cell genome. For now, the only ethically acceptable operation is an injection of hESCs into mouse embryos in the case of pluripotency evaluation [ ]. Pioneering scientific and medical advances always have to be carefully policed in order to make sure they are both ethical and safe.
Because stem cell therapy already has a large impact on many aspects of life, it should not be treated differently. Currently, there are several challenges concerning stem cells. First, the most important one is about fully understanding the mechanism by which stem cells function first in animal models. This step cannot be avoided.
For the widespread, global acceptance of the procedure, fear of the unknown is the greatest challenge to overcome. The efficiency of stem cell-directed differentiation must be improved to make stem cells more reliable and trustworthy for a regular patient. The scale of the procedure is another challenge. Future stem cell therapies may be a significant obstacle. Transplanting new, fully functional organs made by stem cell therapy would require the creation of millions of working and biologically accurate cooperating cells.
Bringing such complicated procedures into general, widespread regenerative medicine will require interdisciplinary and international collaboration. Immunological rejection is a major barrier to successful stem cell transplantation. With certain types of stem cells and procedures, the immune system may recognize transplanted cells as foreign bodies, triggering an immune reaction resulting in transplant or cell rejection.
Further development and versatility of stem cells may cause reduction of treatment costs for people suffering from currently incurable diseases. When facing certain organ failure, instead of undergoing extraordinarily expensive drug treatment, the patient would be able to utilize stem cell therapy.
The effect of a successful operation would be immediate, and the patient would avoid chronic pharmacological treatment and its inevitable side effects. Although these challenges facing stem cell science can be overwhelming, the field is making great advances each day.
Stem cell therapy is already available for treating several diseases and conditions. Their impact on future medicine appears to be significant. After several decades of experiments, stem cell therapy is becoming a magnificent game changer for medicine.
With each experiment, the capabilities of stem cells are growing, although there are still many obstacles to overcome. Regardless, the influence of stem cells in regenerative medicine and transplantology is immense. Currently, untreatable neurodegenerative diseases have the possibility of becoming treatable with stem cell therapy.
Tissue banks are becoming increasingly popular, as they gather cells that are the source of regenerative medicine in a struggle against present and future diseases.
With stem cell therapy and all its regenerative benefits, we are better able to prolong human life than at any time in history. Embryonic stem cells derived from morulae, inner cell mass, and blastocysts of mink: comparisons of their pluripotencies. Embryo Dev. Stem cell therapy in treatment of different diseases.
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