All of the organs in our body rely on stem cells in order to maintain their function. Adult stem cells found in tissues or organs are a self-sustaining population of cells whose offspring make all of the specialized cell types within a tissue. Blood stem cells drive the production of blood, and are used in treatments and therapies such as bone marrow transplantations. However, blood stem cells in humans are not fully understood, with even some of the most basic questions, such as how many cells there are and how they change with age, not yet answered.
For the first time, scientists have been able to determine how many blood stem cells are actively contributing in a healthy human. Researchers adapted a method traditionally used in ecology for tracking population size to estimate that a healthy adult has between 50, and , stem cells contributing to their blood cells at any one time. These cells are used in procedures such as bone marrow transplants. These help people with cancer make new blood cells after their own hematopoietic stem cells have been killed by radiation therapy and chemotherapy.
They may also be used to treat people with conditions such as Fanconi anemia. This is a blood disorder that causes the body's bone marrow to fail.
Stem cells may help your health in the future in many ways and through many new treatments. Researchers think that stem cells will be used to help create new tissue. For example, one day healthcare providers may be able to treat people with chronic heart disease. They can do this by growing healthy heart muscle cells in a lab and transplanting them into damaged hearts.
Other treatments could target illnesses such as type 1 diabetes, spinal cord injuries, Alzheimer disease, and rheumatoid arthritis. New medicines could also be tested on cells made from pluripotent stem cells. Stem cells need much more study before their use can be expanded. Scientists must first learn more about how embryonic stem cells develop. This will help them understand how to control the type of cells created from them.
Another challenge is that the embryonic stem cells available today are likely to be rejected by the body. And some people find it morally troubling to use stem cells that come from embryos. 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. Acta Medica Iranica. Quality guidelines for clinical-grade human induced pluripotent stem cell lines. Regenerative Med. Amps K, Andrews PW, et al. Screening ethnically diverse human embryonic stem cells identifies a chromosome 20 minimal amplicon conferring growth advantage.
Google Scholar. Amit M, Itskovitz-Eldor J. Atlas of human pluripotent stem cells: derivation and culturing. New York: Humana Press; Feeder-independent culture of human embryonic stem cells. Nat Methods. Kang MI. Transitional CpG methylation between promoters and retroelements of tissue-specific genes during human mesenchymal cell differentiation. Cell Biochem. Quality control during manufacture of a stem cell therapeutic. BioProcess Int. Bloushtain-Qimron N. Epigenetic patterns of embryonic and adult stem cells.
Cell Cycle. Brindley DA. Peak serum: implications of serum supply for cell therapy manufacturing. Regenerative Medicine. Solter D, Knowles BB. Immunosurgery of mouse blastocyst. Differentiating embryonic stem cells into embryoid bodies. Methods Mole Biol. Hematopoietic cell differentiation from embryonic and induced pluripotent stem cells. Stem Cell Res Ther. The in vitro development of blastocyst-derived embryonic stem cell lines: formation of the visceral yolk sac, blood islands, and myocardium.
J Embryol Exp Morphol. Kurosawa HY. Methods for inducing embryoid body formation: in vitro differentiation system of embryonic stem cells. J Biosci Bioeng. Derivation, characterization, and differentiation of human embryonic stem cells. Stem Cells.
Edges of human embryonic stem cell colonies display distinct mechanical properties and differentiation potential. Sci Rep. PubMed Google Scholar. Human embryonic stem cell lines generated without embryo destruction. Cell Stem Cell.
Derivation of human embryonic stem cells from developing and arrested embryos. Passaging and colony expansion of human pluripotent stem cells by enzyme-free dissociation in chemically defined culture conditions. Nat Protoc. In: Turksen K, editor.
Human embryonic stem cell protocols. Methods in molecular biology: Humana Press; Mechanical dissociation of human embryonic stem cell colonies by manual scraping after collagenase treatment is much more detrimental to cellular viability than is trypsinization with gentle pipetting.
Biotechnol Appl Biochem. Facilitated expansion of human embryonic stem cells by single-cell enzymatic dissociation. Karyotypic stability, genotyping, differentiation, feeder-free maintenance, and gene expression sampling in three human embryonic stem cell lines deri. Stem Cells Dev. A ROCK inhibitor permits survival of dissociated human embryonic stem cells.
Nat Biotechnol. Scalable passaging of adherent human pluripotent stem cells. Embryonic stem cell lines derived from human blastocysts. Human embryonic stem cellsexpress an immunogenic nonhuman sialic acid. Inhibition of pluripotential embryonic stem cell differentiation by purified polypeptides.
Feeder-free growth of undifferentiated human embryonic stem cells. Nature Biotechnol. Synthetic serum substitute SSS : a globulin-enriched protein supplement for human embryo culture. Assist Reprod Genet.
Chemically defined conditions for human iPSC derivation and culture. Sommer CA, Mostoslavsky G. Experimental approaches for the generation of induced pluripotent stem cells. Takahashi K, Yamanaka S. Induced pluripotent stem cells in medicine and biology.
Buffalos Bubalus bubalis cloned by nuclear transfer of somatic cells. Gurdon JB. The developmental capacity of nuclei taken from intestinal epithelium cells of feeding tadpoles. CAS Google Scholar. Kain K. The birth of cloning: an interview with John Gurdon.
Dis Model Mech. Expression of a single transfected cDNA converts fibroblasts to myoblasts. Genome sequencing of mouse induced pluripotent stem cells reveals retroelement stability and infrequent DNA rearrangement during reprogramming. Directly reprogrammed fibroblasts show global epigenetic remodeling and widespread tissue contribution. Nat Cell Biol. In vivo reprogramming of adult pancreatic exocrine cells to beta-cells.
Mesenchymal stem cells and progenitor cells in connective tissue engineering and regenerative medicine: is there a future for transplantation? Langenbecks Arch Surg. Zhang Wendy, Y. Teratoma formation: a tool for monitoring pluripotency in stem cell research. StemBook, ed. The Stem Cell Research Community. June 12, Single cell transcriptional profiling reveals heterogeneity of human induced pluripotent stem cells.
J Clin Invest. Isolation of human embryonic stem cell-derived teratomas for the assessment of pluripotency. Curr Protoc Stem Cell Biol. Growth of teratomas derived from human pluripotent stem cells is influenced by the graft site. Przyborski SA. Differentiation of human embryonic stem cells after transplantation in immune-deficient mice. Derivation of xeno-free and GMP-grade human embryonic stem cells- platforms for future clinical applications.
PLoS One. Cohen DE, Melton D. Turning straw into gold: directing cell fate for regenerative medicine. Nat Rev Genet. Controlled differentiation of stem cells. Adv Drug Deliv Rev. Turner N, Grose R. Fibroblast growth factor signalling: from development to cancer. Nat Rev Cancer. Rao TP, Kuhl M. An updated overview on Wnt signaling pathways: a prelude for more. Circ Res. Moustakas A, Heldin CH. The regulation of TGFbeta signal transduction. Self-renewal and cell lineage differentiation strategies in human embryonic stem cells and induced pluripotent stem cells.
Expert Opin Biol Ther. Pancreatic endoderm derived from human embryonic stem cells generates glucose-responsive insulin-secreting cells in vivo. Nodal inhibits differentiation of human embryonic stem cells along the neuroectodermal default pathway. Dev Biol. Highly efficient directed differentiation of human induced pluripotent stem cells into cardiomyocytes. Methods Mol Biol. Directed differentiation of human embryonic stem cells into functional hepatic cells.
Directing human embryonic stem cell differentiation towards a renal lineage generates a selforganizing kidney. Efficient generation of lung and airway epithelial cells from human pluripotent stem cells.
Directing lung endoderm differentiation in pluripotent stem cells. Directed differentiation of embryonic stem cells into motor neurons. Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro. Directed differentiation of human embryonic stem cells toward chondrocytes. Protocol for directed differentiation of human pluripotent stem cells toward a hepatocyte fate.
Small-molecule modulators of hedgehog signaling: identification and characterization of smoothened agonists and antagonists. J Biol. Mechanosensitive hair celllike cells from embryonic and induced pluripotent stem cells. In vitro differentiation of retinal cells from human pluripotent stem cells by small-molecule induction. J Cell Sci. Control of stem cell fate and function by engineering physical microenvironments.
Intergr Biol Camb. Preferential gene expression and epigenetic memory of induced pluripotent stem cells derived from mouse pancreas. Genes Cells. F, National Clinical H, E. The procurement of cells for the derivation of human embryonic stem cell lines for therapeutic use: recommendations for good practice.
Stem Cell Rev. Stem Cell Res. Stem Cell Rep. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells. Nat Genet. Human embryonic stem cell-derived cardiac progenitors for severe heart failure treatment: first clinical case report.
Eur Heart J. Ilic D, Ogilvie C. Concise review: human embryonic stem cells-what have we done? What are we doing? Where are we going? Rocha V, et al. Clinical use of umbilical cord blood hematopoietic stem cells.
Biol Blood Marrow Transplant. Sports Med Arthrosc — Achilles tendinopathy. Sports Med Arthrosc. Biological augmentation for tendon repair: lessons to be learned from development, disease, and tendon stem cell research.
Cell engineering and regeneration. Reference Series in Biomedical Engineering. Cham: Springer; J Cell Physiol. Articular cartilage defects: study of 25, knee arthroscopies.
Stem cell therapy for treating osteonecrosis of the femoral head: from clinical applications to related basic research. Stem Cell Res Therapy. Autologous bone marrow cell implantation in the treatment of non-traumatic osteonecrosis of the femoral head: five year follow-up of a prospective controlled study.
Treatment of early stage osteonecrosis of the femoral head with autologous implantation of bone marrow-derived and cultured mesenchymal stem cells. Early results of core decompression and autologous bone marrow mononuclear cells instillation in femoral head osteonecrosis: a randomized control study.
J Arthroplast. Rejuvenating senescent and centenarian human cells by reprogramming through the pluripotent state. Genes Dev. Sahin E, Depinho RA. Linking functional decline of telomeres, mitochondria and stem cells during ageing. Using DNA methylation profiling to evaluate biological age and longevity interventions.
Cell Metab.
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