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One of the main challenges of tissue engineering in dentistry is to replace bone and dental tissues with strategies or techniques that simulate physiological tissue repair conditions. This systematic review of in vitro studies aimed to evaluate the influence of the addition of nanohydroxyapatite (NHap) to scaffolds on cell proliferation and osteogenic and odontogenic differentiation of human mesenchymal stem cells. In vitro studies on human stem cells that proliferated and differentiated into odontogenic and osteogenic cells in scaffolds containing NHap were included in this study. Searches in PubMed/MEDLINE, Scopus, Web of Science, OpenGrey, ProQuest, and Cochrane Library electronic databases were performed. The total of 333 articles was found across all databases. After reading and analyzing titles and abstracts, 8 articles were selected for full reading and extraction of qualitative data. Results showed that despite the large variability in scaffold composition, NHap-containing scaffolds promoted high rates of cell proliferation, increased alkaline phosphatase (ALP) activity during short culture periods, and induced differentiation, as evidenced by the high expression of genes involved in osteogenesis and odontogenesis. However, further studies with greater standardization regarding NHap concentration, type of scaffolds, and evaluation period are needed to observe possible interference of these criteria in the action of NHap on the proliferation and differentiation of human stem cells.
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Objective:To investigate the role of nicotinamide (NIC) in the differentiation of neural crest cells from human embryonic stem cells (hESCs), and lay the foundation for the induction of hESC-derived corneal endothelial cells.Methods:hESCs line H1 cultured for 5-7 days was used for induction.According to the different components of the neural crest induction medium, cells were assigned into different groups for 7-days induction, including group treated without NIC cultured in induction medium only, group treated with NIC cultured in induction medium containing 10 mmol/L NIC, NIC+ resveratrol (Res) group cultured in induction medium containing 10 mmol/L NIC and 10 μmol/L Res and Sirtinol group cultured in induction medium containing 10 μmol/L Sirtinol.Res and Sirtinol were used as SIRT1 activity agonist and inhibitor, respectively.The relative mRNA expression levels of hESCs and neural crest cell markers were detected by real-time fluorescence quantitative PCR at 1, 3, 5 and 7 days during the induction.The expression of neural crest cells markers after 7 days of induction was assayed by immunofluorescence staining.The induction efficiency of NIC and the effect of SIRT1 regulation on human natural killer 1 (HNK-1) positive cells expression were evaluated through flow cytometry analysis of percentages of nerve growth factor receptor (P75) and HNK-1 + cells. Results:Compared with the group treated without NIC, the mRNA expressions of totipotent genes octamer transcription factor 4 (OCT4) and homeodomain proteins (NANOG) were significantly decreased, and the mRNA expression levels of neural crest cell markers P75, HNK-1, SRY-related HMG box (SOX) 9 and SOX10 were significantly increased in the group treated with NIC after 5 days of induction (all at P<0.05). In the group treated without NIC, P75 was weakly expressed, and HNK-1 was sporadically expressed, and transcription factor AP-2β (AP-2β) and paired-like homeodomain transcription factor 2 (PITX2) were not detected.In the group treated with NIC, P75, HNK-1, AP-2β and PITX2 were strongly expressed.The proportion of P75 + HNK-1 + cells and P75 + cells were both significantly higher in the group treated with NIC than without NIC ( t=8.481, P=0.001; t=2.987, P=0.041). The percentage of HNK-1 + cells in groups treated without and with NIC, NIC+ Res group and Sirtinol group were (34.267±12.522)%, (89.633±1.358)%, (64.667±6.429)% and (86.300±3.460)%, respectively, with a statistically significant overall difference ( F=36.799, P<0.001). The proportion of HNK-1 + cells in NIC+ Res group was significantly lower than that in the groups treated with NIC and Sirtinol (all at P<0.05). Conclusions:NIC promotes the differentiation of hESCs-derived neural crest cells by inhibiting the activity of SIRT1 to enhance the expression of HNK-1.NIC treatment may provide a new strategy for source of seed cells in the treatment of neural crest cell-related diseases, such as corneal endothelial transplantation.
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Parthenogenetic embryos, created by activation and diploidization of oocytes, arrest at mid-gestation for defective paternal imprints, which impair placental development. Also, viable offspring has not been obtained without genetic manipulation from parthenogenetic embryonic stem cells (pESCs) derived from parthenogenetic embryos, presumably attributable to their aberrant imprinting. We show that an unlimited number of oocytes can be derived from pESCs and produce healthy offspring. Moreover, normal expression of imprinted genes is found in the germ cells and the mice. pESCs exhibited imprinting consistent with exclusively maternal lineage, and higher X-chromosome activation compared to female ESCs derived from the same mouse genetic background. pESCs differentiated into primordial germ cell-like cells (PGCLCs) and formed oocytes following in vivo transplantation into kidney capsule that produced fertile pups and reconstituted ovarian endocrine function. The transcriptome and methylation of imprinted and X-linked genes in pESC-PGCLCs closely resembled those of in vivo produced PGCs, consistent with efficient reprogramming of methylation and genomic imprinting. These results demonstrate that amplification of germ cells through parthenogenesis faithfully maintains maternal imprinting, offering a promising route for deriving functional oocytes and having potential in rebuilding ovarian endocrine function.
Subject(s)
Animals , Female , Mice , Mice, Transgenic , Mouse Embryonic Stem Cells/metabolism , Oocytes/metabolism , ParthenogenesisABSTRACT
ABSTRACT Degenerative retinal diseases such as retinitis pigmentosa, Stargardt's macular dystrophy, and age-related macular degeneration are characterized by irreversible loss of vision due to direct or indirect photoreceptor damage. No effective treatments exist, but stem cell studies have shown promising results. Our aim with this review was to describe the types of stem cells that are under study, their effects, and the main clinical trials involving them.
RESUMO As doenças degenerativas da retina, como retinose pigmentar, distrofia macular de Stargardt e degeneração macular relaciona à idade, são caracterizadas por perda irre versível da visão devido a danos diretos ou indiretos aos fotorreceptores. Não existem tratamentos eficazes, porém os estudos com células-tronco mostraram resultados promissores. Nosso objetivo com esta revisão foi descrever os tipos de células-tronco em estudo, seus efeitos e os principais ensaios clínicos que as envolvem.
Subject(s)
Humans , Retinal Degeneration/therapy , Pluripotent Stem Cells/transplantation , Stem Cell Transplantation/methods , Retina/cytology , Clinical Trials as Topic , Treatment OutcomeABSTRACT
Objective To explore the effect of concave and convex interface on in vitro culture of mouse embryonic stem cells. Methods Mouse embryonic stem cells were cultured on substrate with concave and convex interface. The biological morphology of cell colony was observed. The pluripotency of embryonic stem cells was detected by immunofluorescence and alkaline phosphatase (ALP) staining. Results Embryonic stem cells on concave substrates and convex substrates had higher stereo degree and circularity than those on flat substrates, but it was more obvious on concave substrates. Besides, the expression level of Oct4-GFP and the staining intensity of ALP in embryonic stem cells which were cultured on concave substrates and convex substrates were significantly higher than those on flat basement, especially on concave substrates. Conclusion sCompared with flat substrates, concave substrates and convex substrates had positive effects on the pluripotency maintenance of embryonic stem cells, which could help to maintain pluripotency, but concave substrates had better effects. Changing the substrate curvature could help to maintain pluripotency of embryonic stem cells cultured in vitro. The research findings are of great significance to the study and clinical application of embryonic stem cells.
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Objective To construct human embryonic stem cell (hESC) line with forkhead box G1 (FOXG1) gene knockout by clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) gene editing technology, and to investigate the role of FOXG1 gene in the early neural induction of hESCs. Methods Two guide RNAs (gRNAs) were transfected to induce FOXG1 gene large fragment knockout in hESCs by CRISPR/Cas9 gene editing technology. FOXG1 gene knockout hESCs were confirmed by monoclonal screening, sequencing and Western blotting analysis. The expression of the key markers including paired box 6 (PAX6), sex-determining region Y-box 2 (SOX2) and orthodenticle homeobox 2 (OTX2) was detected by immunofluorescence staining and qRT-PCR in the early process of neural induction before and after FOXG1 gene knockout. Results hESCs with FOXG1 gene large fragment knockout were successfully obtained by CRISPR/Cas9 gene editing technology. The results of immunofluorescence staining and qRTPCR suggested that FOXG1 deletion did not significantly influence the expression of PAX6, SOX2 and OTX2 during neural induction. Conclusion FOXG1 gene large fragment knockout in hESCs can be quickly induced by a pair of gRNAs cotransfection. FOXG1 deletion has no significant impacts on neural induction of hESCs.
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@#Retinal degenerative disease can lead to decreased vision, which is a blinding ophthalmopathy caused by irreversible damage or apoptosis of retinal pigment epithelium(RPE)cells or photoreceptor cells, often resulting in visual impairment or even blindness. Human embryonic stem cells(hESCs)are a kind of multi-directional differentiation cells. By appropriate methods, hESCs can be differentiated into various retinal cells. Since human PRE cells cannot be regenerated, studies have shown that the clinical treatment of retinopathy with stem cell derived RPE cell transplantation has practical prospects and has made a breakthrough in recent years. Due to the limitations of multiple factors, the selection of methods and the complexity of induction conditions, the efficiency of induced differentiation of RPE and the survival rate after transplantation vary greatly and are unstable. Therefore, the current researches should focus on how to integrate different culture methods, take advantages and eliminate disadvantages, so as to improve the directed differentiation efficiency of hESCs, as well as the number and quality of induced cells, thus reducing culture pollution and immune rejection and so on. Here, we will summarize the current examples of various culture methods and give a review from different perspectives.
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BACKGROUND: The characteristics of laminin that can promote the proliferation of stem cells have been widely concerned. OBJECTIVE: To review the interactions between laminin and many different stem cells, and provide reliable theoretical basis for chondrogenic research and application of stem cells. METHODS: Wanfang, CNKI, PubMed and Web of Science databases were searched for articles related to mechanism of laminin, changes in stem cell behaviors, and cartilage regeneration published from January 2010 to October 2019. The retrieval terms were “laminin” and “steam cells” in Chinese and English. Duplicated and poorly related articles were excluded, and finally 57 articles were included for review. RESULTS AND CONCLUSION: (1) The structural characteristics of laminin were summarized. The spatiotemporal changes of laminin during cartilage development and degradation were analyzed. At the same time, the distribution of laminin expression in natural cartilage tissue and tissue engineered cartilage tissue was compared. (2) The effects of laminin on the proliferation of various stem cells, including embryonic stem cells, induced pluripotent stem cells and adult stem cells, were described. (3) The possible hotspots on the combination of laminin and stem cells for cartilage regeneration were proposed, with the attempt of providing theoretical basis for cartilage repair and regeneration in the future.
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BACKGROUND: In the research of human embryonic stem cells, introducing exogenous molecules such as DNA into cells is a common research method, but the transfection efficiency is relatively low. It is crucial to answer the question of how to optimize the existing conditions to improve the transfection efficiency. OBJECTIVE: To compare the effects of two different passaging methods on H9 transfection efficiency, in order to optimize the conditions required for embryonic stem cell transfection. METHODS: Human embryonic stem cell lines H9 were cultured for 48 hours after small clone passaging or single-cell passaging. Lipofectamine 3000 was used to transfect pAdTrack-AKT1 fluorescent plasmid into human embryonic stem cells. After 2 days of transfection, the expression of fluorescent plasmids was observed by fluorescence microscope and the transfection efficiency was detected by flow cytometry. RT-qPCR and western blot were used to detect the mRNA and protein expression levels of AKT1 respectively. RESULTS AND CONCLUSION: Under the fluorescence microscopy, the number of cells expressing fluorescent plasmids in the single-cell passaging group was more than that in the small clone passaging group, and the flow cytometry analysis showed that the transfection efficiency of cells in the single-cell passaging group was (47.18±2.00)%, which was significantly higher than (19.52±0.86)% in the small clone passaging group (P < 0.01). RT-qPCR and western blot analysis showed that the expression levels of AKT1 mRNA and protein in the single-cell passaging group were significantly higher than those in the small clone passaging group (P < 0.01). These findings indicate that single-cell passaging can increase the contact area between cells and transfection reagent liposomes, and improve the transfection efficiency of human embryonic stem cells.
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BACKGROUND: Exosomes contain DNA fragments, mRNA, miRNA, functional proteins, transcription factors and other substances with biological activities. Their membrane structure also expresses a variety of antigens and antibody molecules, thus producing various biological effects. Recent studies have shown that it has similar therapeutic effects with stem cell transplantation and can be used as a substitute of stem cell transplantation in the treatment of cardiovascular diseases. OBJECTIVE: To summarize the application of exosomes from different stem cells in the treatment of cardiovascular diseases, so as to provide reference and basis for exosomes applied in the treatment of cardiovascular diseases. METHODS: Articles in PubMed database from 2005 to 2019 were searched using the search terms of “exosomes, cardiovascular diseases, embryonic stem cells, induced pluripotent stem cells, mesenchymal stem cells.” Articles in databases of CNKI and VIP from 2014 to 2019 were retrieved with the search terms of “exosome, cardiovascular disease, embryonic stem cells, induced pluripotent stem cells, mesenchymal stem cells.” The literature and references were reviewed one by one. RESULTS AND CONCLUSION: Exosomes derived from stem cells are safer and more effective than stem cell transplantation, and have great potential in the prevention and treatment of cardiovascular diseases. However, the research on the function and use of exosomes is still in its infancy. In addition, low exosome content and cumbersome extraction process limit its clinical application.
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BACKGROUND: Autoimmune diseases are a class of diseases that cause a strong immune response to the continuous lack of self-tissue-specific antigens in the thymus. Hypothyroidism and unstable expression of tissue-specific antigens in the thymus can limit the therapeutic effect. The thymus is mainly composed of thymic epithelial cells, but the limited number of mature thymic epithelial cells and thymic epithelial progenitor cells in the thymus has greatly limited related research. OBJECTIVE: To detect the expression of autoimmune regulator (AIRE) when mouse embryonic stem cells were transformed into thymic epithelial progenitor cells. METHODS: A two-step differentiation method was used to induce the differentiation of mouse embryonic stem cells into endoderm and then into thymic epithelial progenitor cells. The cells were collected at 0, 3, and 13 days of induced differentiation. Immunofluorescence, flow cytometry, western blot and real-time PCR were used to detect the expression of cell-associated genes and proteins. RESULTS AND CONCLUSION: Positive expression of OCT4 and SSEA1 was detected by immunofluorescence at 0 day of induction. The double positive expression of SOX17 and FoxA2 was measured by immunofluorescence at 3 days of induction. The positive expression of EpCAM, K5 and K8 were analyzed by flow cytometry at 13 days of induction. During the directional differentiation of mouse embryonic stem cells, real-time PCR indicated that the expression of PAX1, PAX9, FOXN1 and PLET1 showed an increasing trend. The expression of AIRE gene increased significantly at 0, 3, and 13 days of induction. At the same time, the expression of INS2 gene and GAD67 gene also increased. Western blot assay showed that the expression of AIRE protein gradually decreased at 0, 3, and 13 days of induction; however, insulin protein and GAD67 protein were not detected. Overall findings indicate that mouse embryonic stem cells can successfully differentiate into thymic epithelial progenitor cells with highly expressed AIRE gene, which promotes the expression of INS2 and GAD67 genes, and provides an evaluation basis for cell transplantation in the treatment of autoimmune diseases.
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Dysregulation of circadian rhythms associates with cardiovascular disorders. It is known that deletion of the core circadian gene Bmal1 in mice causes dilated cardiomyopathy. However, the biological rhythm regulation system in mouse is very different from that of humans. Whether BMAL1 plays a role in regulating human heart function remains unclear. Here we generated a BMAL1 knockout human embryonic stem cell (hESC) model and further derived human BMAL1 deficient cardiomyocytes. We show that BMAL1 deficient hESC-derived cardiomyocytes exhibited typical phenotypes of dilated cardiomyopathy including attenuated contractility, calcium dysregulation, and disorganized myofilaments. In addition, mitochondrial fission and mitophagy were suppressed in BMAL1 deficient hESC-cardiomyocytes, which resulted in significantly attenuated mitochondrial oxidative phosphorylation and compromised cardiomyocyte function. We also found that BMAL1 binds to the E-box element in the promoter region of BNIP3 gene and specifically controls BNIP3 protein expression. BMAL1 knockout directly reduced BNIP3 protein level, causing compromised mitophagy and mitochondria dysfunction and thereby leading to compromised cardiomyocyte function. Our data indicated that the core circadian gene BMAL1 is critical for normal mitochondria activities and cardiac function. Circadian rhythm disruption may directly link to compromised heart function and dilated cardiomyopathy in humans.
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Dysregulation of circadian rhythms associates with cardiovascular disorders. It is known that deletion of the core circadian gene Bmal1 in mice causes dilated cardiomyopathy. However, the biological rhythm regulation system in mouse is very different from that of humans. Whether BMAL1 plays a role in regulating human heart function remains unclear. Here we generated a BMAL1 knockout human embryonic stem cell (hESC) model and further derived human BMAL1 deficient cardiomyocytes. We show that BMAL1 deficient hESC-derived cardiomyocytes exhibited typical phenotypes of dilated cardiomyopathy including attenuated contractility, calcium dysregulation, and disorganized myofilaments. In addition, mitochondrial fission and mitophagy were suppressed in BMAL1 deficient hESC-cardiomyocytes, which resulted in significantly attenuated mitochondrial oxidative phosphorylation and compromised cardiomyocyte function. We also found that BMAL1 binds to the E-box element in the promoter region of BNIP3 gene and specifically controls BNIP3 protein expression. BMAL1 knockout directly reduced BNIP3 protein level, causing compromised mitophagy and mitochondria dysfunction and thereby leading to compromised cardiomyocyte function. Our data indicated that the core circadian gene BMAL1 is critical for normal mitochondria activities and cardiac function. Circadian rhythm disruption may directly link to compromised heart function and dilated cardiomyopathy in humans.
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Dysregulation of circadian rhythms associates with cardiovascular disorders. It is known that deletion of the core circadian gene Bmal1 in mice causes dilated cardiomyopathy. However, the biological rhythm regulation system in mouse is very different from that of humans. Whether BMAL1 plays a role in regulating human heart function remains unclear. Here we generated a BMAL1 knockout human embryonic stem cell (hESC) model and further derived human BMAL1 deficient cardiomyocytes. We show that BMAL1 deficient hESC-derived cardiomyocytes exhibited typical phenotypes of dilated cardiomyopathy including attenuated contractility, calcium dysregulation, and disorganized myofilaments. In addition, mitochondrial fission and mitophagy were suppressed in BMAL1 deficient hESC-cardiomyocytes, which resulted in significantly attenuated mitochondrial oxidative phosphorylation and compromised cardiomyocyte function. We also found that BMAL1 binds to the E-box element in the promoter region of BNIP3 gene and specifically controls BNIP3 protein expression. BMAL1 knockout directly reduced BNIP3 protein level, causing compromised mitophagy and mitochondria dysfunction and thereby leading to compromised cardiomyocyte function. Our data indicated that the core circadian gene BMAL1 is critical for normal mitochondria activities and cardiac function. Circadian rhythm disruption may directly link to compromised heart function and dilated cardiomyopathy in humans.
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@#【Objective】 A human embryonic stem cell line derived from Preimplantation genetic testing （PGT） embryos was established in a xeno- free stem cell culture system to provide disease models for medical research. 【Methods】The xeno-free culture system using xeno-free human foreskin fibroblast feeder layers（XF-HFF）mixed with commercially available chemically-defined medium（CDM）was assessed. In the culture system，a new hESC cell line was established using discarded embryos derived from PGT in patients with chromosomal balance translocation.【Results】The new availabled stem cell line was successfully cultured in the xeno-free culture system for a long time（> 45 passages）. The karyotype analysis revealed that the new line kept the same karyotype over 45 passages. Moreover，the expression of pluripotent markers was detected by fluorescent immunostaining including SSEA- 3，SSEA- 4，SSEA- 1，TRA- 1- 60， and TRA-1-81. RT-PCR analysis showed that the stem cell markers were present in hESC grown on XF-HFF-CDM. In addition，the teratoma formation analysis demonstrated that the cells cultured in XF-HFF/CDM maintained their pluripotency in vivo.【Conclusions】Our study may provide the possibility to establish embryonic stem cells with certain pathogenic genes，which could be applied for clinical research and treatment.
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The establishment and development of gene knockout mice have provided powerful support for the study of gene function and the treatment of human diseases. Gene targeting and gene trap are two techniques for generating gene knockout mice from embryonic stem cells. Gene targeting replaces endogenous knockout gene by homologous recombination. There are two ways to knock out target genes: promoter trap and polyA trap. In recent years, many new gene knockout techniques have been developed, including Cre/loxP system, CRISP/Cas9 system, latest ZFN technology and TALEN technology. This article focuses on the several new knockout mouse techniques.
Subject(s)
Animals , Humans , Mice , Disease Models, Animal , Embryonic Stem Cells , Gene Knockout Techniques , Gene Targeting , Homologous Recombination , Mice, KnockoutABSTRACT
Parthenogenetic embryonic stem cells (pESCs) derived from bi-maternal genomes do not have competency of tetraploid complementation, due to lacking of paternal imprinting genes. To make pESCs possess fully development potentials and similar pluripotency to zygote-derived ESCs, we knocked out one allelic gene of the two essential maternal imprinting genes (H19 and IG) in their differentially methylated regions (DMR) via CRISPR/Cas9 system and obtained double knock out (DKO) pESCs. Maternal pESCs had similar morphology, expression levels of pluripotent makers and in vitro neural differentiation potentials to zygotes-derived ESCs. Besides that, DKO pESCs could contribute to full-term fetuses through tetraploid complementation, proving that they held fully development potentials. Derivation of DKO pESCs provided a type of major histocompatibility complex (MHC) matched pluripotent stem cells, which would benefit research in regenerative medicine.
Subject(s)
Animals , Mice , Embryonic Stem Cells , Gene Knockout Techniques , Genomic Imprinting , Parthenogenesis , Pluripotent Stem Cells , Regenerative Medicine , TetraploidyABSTRACT
Previously, the majority of human embryonic stem cells and human induced pluripotent stem cells have been derived on feeder layers and chemically undefined medium. Those media components related to feeder cells, or animal products, often greatly affect the consistency of the cell culture. There are clear advantages of a defined, xeno-free, and feeder-free culture system for human pluripotent stem cells (hPSCs) cultures, since consistency in the formulations prevents lot-to-lot variability. Eliminating all non-human components reduces health risks for downstream applications, and those environments reduce potential immunological reactions from stem cells. Therefore, development of feeder-free hPSCs culture systems has been an important focus of hPSCs research. Recently, researchers have established a variety of culture systems in a defined combination, xeno-free matrix and medium that supports the growth and differentiation of hPSCs. Here we described detailed hPSCs culture methods under feeder-free and chemically defined conditions using vitronetin and TeSR-E8 medium including supplement bioactive lysophospholipid for promoting hPSCs proliferation and maintaining stemness.
Subject(s)
Animals , Humans , Cell Culture Techniques , Embryonic Stem Cells , Extracellular Matrix , Feeder Cells , Human Embryonic Stem Cells , Induced Pluripotent Stem Cells , Pluripotent Stem Cells , Stem CellsABSTRACT
BACKGROUND AND OBJECTIVES: Embryonic stem (ES) cells have pluripotent ability to differentiate into multiple tissue lineages. SIRT1 is a class III histone deacetylase which modulates chromatin remodeling, gene silencing, cell survival, metabolism, and development. In this study, we examined the effects of SIRT1 inhibitors on the hematopoietic differentiation of mouse ES cells. METHODS AND RESULTS: Treatment with the SIRT1 inhibitors, nicotinamide and splitomicin, during the hematopoietic differentiation of ES cells enhanced the production of hematopoietic progenitors and slightly up-regulated erythroid and myeloid specific gene expression. Furthermore, treatment with splitomicin increased the percentage of erythroid and myeloid lineage cells. CONCLUSIONS: Application of the SIRT1 inhibitor splitomicin during ES cell differentiation to hematopoietic cells enhanced the yield of specific hematopoietic lineage cells from ES cells. This result suggests that SIRT1 is involved in the regulation of hematopoietic differentiation of specific lineages and that the modulation of the SIRT1 activity can be a strategy to enhance the efficiency of hematopoietic differentiation.
Subject(s)
Animals , Mice , Cell Differentiation , Cell Survival , Chromatin Assembly and Disassembly , Gene Expression , Gene Silencing , Histone Deacetylases , Metabolism , Mouse Embryonic Stem Cells , NiacinamideABSTRACT
Stem cells are attracting attention as a key element in future medicine, satisfying the desire to live a healthier life with the possibility that they can regenerate tissue damaged or degenerated by disease or aging. Stem cells are defined as undifferentiated cells that have the ability to replicate and differentiate themselves into various tissues cells. Stem cells, commonly encountered in clinical or preclinical stages, are largely classified into embryonic, adult, and induced pluripotent stem cells. Recently, stem cell transplantation has been frequently applied to the treatment of pain as an alternative or promising approach for the treatment of severe osteoarthritis, neuropathic pain, and intractable musculoskeletal pain which do not respond to conventional medicine. The main idea of applying stem cells to neuropathic pain is based on the ability of stem cells to release neurotrophic factors, along with providing a cellular source for replacing the injured neural cells, making them ideal candidates for modulating and possibly reversing intractable neuropathic pain. Even though various differentiation capacities of stem cells are reported, there is not enough knowledge and technique to control the differentiation into desired tissues in vivo. Even though the use of stem cells is still in the very early stages of clinical use and raises complicated ethical problems, the future of stem cells therapies is very bright with the help of accumulating evidence and technology.