Mesenchymal Stem Cells from the Deciduous Tooth Pulp Lose their Ability to Suppress the Differentiation of Dendritic Cells during Long-Term Culturing.

A culture of cells expressing markers of mesenchymal stem cells (MSC) (CD73, CD90, CD44, CD29, and CD49b), but not hematopoietic cell markers, and capable of multilineage differentiation was isolated from the deciduous tooth pulp. Co-culturing with immature dendritic cells in the presence of LPS did not reveal an ability of the MSC to suppress the maturation of dendritic cells. On the contrary, co-culturing of MSC with monocytes in the presence of granulocyte-macrophage CSF and IL-4 led to complete suppression of monocyte differentiation into dendritic cells. However, long-term culturing of MSC from dental pulp showed that by the passage 11, they almost completely lose their suppressor ability. These results indicate that the immunological properties of MSC can change during culturing without changing their phenotypic markers. This should be taken into account when creating biomedical cell products.

Intense orthodontic force induces the three dental pulp nitric oxide synthase isoforms and leads to orofacial discomfort in rats.

OBJECTIVE: The objective of this study was to evaluate the role of nitric oxide synthase (NOS) isoforms influence during tooth movement with different forces. SETTINGS AND SAMPLE POPULATION: 100 male Wistar rats (n = 10/group) were divided into a Sham group (animals not submitted to device installation nor Induced Toot Movement [ITM]), Negative Control Group (NCG) (animals submitted to device installation but not to ITM) and three experimental groups (F1, F2 and F3) (submitted to ITM with forces of 25, 50 and 100 gF respectively). MATERIALS AND METHODS: A daily count of biting and scratching on the vibrissae and the Grimace scale were applied. After 4 (D4) and 11 (D11) days, the molar diastema was measured, and the animals were euthanized for histological (vascular parameters) and immunohistochemistry (iNOS, eNOS and nNOS) in the dental pulp. RESULTS: On D4, there was significant movement in the F3 group (P = .001) and on D11 in F1, F2 and F3 (P < .001). The number of bites (P < .001) and scratching (P = .006) was higher in F2-F3, and F3 had higher Grimace scores (P < .001) and weight loss (P < .001). At D4, there was an increase in pulp ectasia in F2-F3 (P = .021) and a reduction in the number of vessels in F3 (P = .005). In D4 and D11, there was a significant increase in immunostaining for iNOS and eNOS in F1 (P = .025 and P < .001 respectively) and F2 (P = .007 and P < .001 respectively). At D4, F2 and F3 showed higher immunostaining for nNOS (P = .027). CONCLUSION: Thus, IDM induced inflammatory changes in the dental pulp reflecting in force-dependent pain/suffering signs.

Effects of mechanical force on proliferation and apoptosis of stem cells from human exfoliated deciduous teeth.

OBJECTIVES: This study was designed to explore the effects of mechanical force on the proliferation, apoptosis, and morphology of stem cells from human exfoliated deciduous tooth pulp (SHEDs). MATERIALS AND METHODS: Caries-free stranded deciduous teeth were extracted, and SHEDs were isolated through enzymatic digestion. The cultured SHEDs were subjected to different levels of mechanical stimuli (0, 100, 200, and 300 g) for 7 days (30 min/day) using external centrifugal force. Cell proliferation was evaluated with the CCK-8 assay, and the cell cycle and apoptosis were assessed by flow cytometry. The cell morphology was examined using transmission electron microscopy. RESULTS: Cell proliferation assay showed no differences between the three stimulation groups and the control group in day 1 to day 3. From the 4th day, cell proliferation was significantly lower in the mechanical force groups than in the control group, but no significant difference was observed among the three mechanical force groups. Besides, there was no significant difference in cell apoptosis among the four groups for 7 days. On day 7 after stimulation, the SHEDs were shrunken, with significantly increased isochromosome in the nucleus and an increase in lysosomes. CONCLUSIONS: Mechanical force can inhibit the proliferation and affect morphology of SHEDs, but it has no effect on cell apoptosis. CLINICAL RELEVANCE: Mechanical force stimulation significantly inhibited cell proliferation of SHEDs. Mechanical force stimulation had no significant effect on cell apoptosis of SHEDs. The morphology and ultrastructure of SHEDs changed after mechanical force stimulation.

Effects of rice fermented extracts, "Sake Lees", on the functional activity of odontoblast-like cells (KN-3 cells).

This study was designed to investigate the effects of Sake Lees extracts (SLE, Sake Kasu) on the functional activity of odontoblastic cells and tooth pulp of the rats. For in vitro studies, a rat clonal odontoblast-like cell line, KN-3 cells were cultured. SLE significantly decreased KN-3 cell proliferation, but showed no significant cytotoxicity. SLE effects on several protein productions of KN-3 cells were compared with PBS. SLE and PBS increased alkaline phosphatase (ALP), dentin sialoprotein (DSP), and osterix in a day-course dependent manner, while SLE increased the induction of ALP on day 9-21 and DSP on day 15-21. SLE also increased Runx2 expression on day 3 and 9 compared to PBS. Alizarin Red stainings revealed that SLE showed a subtle increase in mineralization of KN-3 cells on day 15 and 21. A histological investigation was conducted to assess if SLE induced reparative dentin formation after direct capping at the exposed tooth pulp in rats, suggesting that SLE could increase the reparative dentin formation more than PBS. These findings suggest that Sake Lees could have functional roles in the alterations of odontoblastic activity, which might influence the physiology of the tooth pulp.

Potentiality and Inflammatory Marker Expression Are Maintained in Dental Pulp Cell Cultures from Carious Teeth.

OBJECTIVES: This investigation aimed to isolate and culture human dental pulp cells from carious teeth (cHDPCs) and compare their growth characteristics, colony-forming efficiency, mineralization potential and gene expression of Toll-like receptors (TLR)-2, TLR-4, TLR-9, tumour necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, IL-8, IL-17A, 1L-17R, IL-23A, nuclear factor-kappa B (NF-κB), mitogen-activated protein kinase (MAPK1), dentin matrix protein (DMP)-1, dentin sialophospho protein (DSPP), sex determining region Y-box 2 (SOX2) and marker of proliferation Ki-67 (MKi67) with cells isolated from healthy or non-carious teeth (ncHDPCs). METHODS: Pulp tissues were obtained from both healthy and carious teeth (n = 5, each) to generate primary cell lines using the explant culture technique. Cell cultures studies were undertaken by generating growth curves, a colony forming unit and a mineralization assay analysis. The expression of vimentin was assessed using immunocytochemistry (ICC), and the gene expression of above-mentioned genes was determined using quantitative real-time reverse-transcription polymerase chain reaction. RESULTS: ncHDPCs and cHDPCs were successfully isolated and cultured from healthy and inflamed human dental pulp tissue. At passage 4, both HDPC types demonstrated a typical spindle morphology with positive vimentin expression. No statistical difference was observed between ncHDPCs and cHDPCs in their growth characteristics or ability to differentiate into a mineralizing phenotype. ncHDPCs showed a statistically significant higher colony forming efficiency than cHDPCs. The gene expression levels of TLR-2, TLR-4, TLR-9, TNF-α, IL-6, IL-8, IL-17R, IL-23A, NF-κB, MAPK1, DMP1, DSPP and SOX2 were significantly higher in cHDPCs compared with ncHDPC cultures. CONCLUSION: cHDPCs retain their differentiation potential and inflammatory phenotype in vitro. The inflamed tooth pulp contains viable stem/progenitor cell populations which have the potential for expansion, proliferation and differentiation into a mineralizing lineage, similar to cells obtained from healthy pulp tissue. These findings have positive implications for regenerative endodontic procedures.

Evaluation of the response to electric pulp testing in multiple sclerosis patients without a history of trigeminal neuralgia: a case-control study.

BACKGROUND: The importance of evaluating the pulpal threshold to electrical stimulation, as a side effect of probable neuropathy in Multiple Sclerosis (MS) patients is a novel issue. This study aimed to investigate electrical pulp test thresholds in MS patients without a history of trigeminal neuralgia compared to healthy individuals. METHODS: Sixty-nine maxillary central incisors, belonging to 34 relapsing-remitting MS patients, and 35 healthy individuals were included in this survey. The MS patients matched for intended variables, were 22-50 years old, had a more than 1-year history of MS, no history of trigeminal neuralgia and/or other neuropathy. The electric pulp sensibility test was performed on all samples. Electric pulp testing (EPT) results were recorded based on the pulp tester's grade that evoked a response. Data were analyzed with paired T-test, Mann-Whitney test, and Spearman correlation (P < 0.05). RESULTS: According to the results of this study, the mean values of response to EPT were 1.2 ± 0.5 and 1.8 ± 0.5 in MS patients and healthy individuals, respectively. The pulpal response to EPT between the two groups was significantly different (P < 0.0001). CONCLUSIONS: MS patients showed a significantly reduced response to the electric pulp test in their maxillary central incisors in comparison to matched healthy persons.

Metalloproteinase 14 (MMP-14) and hsa-miR-410-3p expression in human inflamed dental pulp and odontoblasts.

The objective of this study is to evaluate MMP-14 expression in odontoblasts and in the bulk of dental pulp of teeth with pulpitis; to determine the expression of microRNA-410 (miR-410) in pulp tissue, since sequence analysis suggests that miR-410 has potential binding site on MMP-14's 3'UTR, and hence, can regulate expression of the latter one. Tissue samples of dental pulp from teeth with pulpitis and healthy (control) were formalin fixed and paraffin embedded (FFPE). Samples were examined using immunohistochemical staining for MMP-14 and the expression of miR-410 was evaluated using qRT-PCR. In both, healthy and inflamed pulp odontoblasts stained more intensively than remaining pulp tissue, but this difference was not statistically significant. More positive staining was observed in inflamed pulps compared to healthy pulps. Expression of miR-410 was found significantly lower in inflamed pulps than in healthy ones. In the two examined zones, odontoblasts and remaining pulp, miR-410 was expressed on a similar level. No statistically significant correlation of miR-410 and MMP-14 expression was found. We showed that inflammation changes the MMP-14 expression in pulp tissue and odontoblasts. This study demonstrates for the first time miR-410 expression in human dental pulp and that expression of this microRNA was downregulated in inflamed dental pulp and odontoblasts.

Effect of Bioactive Peptide Complex Isolated from Bovine Serum on Proliferation and Migration of Mesenchymal Stromal Cells In Vitro and Reparation of Bone Defects In Vivo.

We studied the effect of a bioactive peptide complex isolated from bovine serum on the proliferative potential and migration rate of mesenchymal stromal cells in vitro, as well as on the healing of modeled bone defects in rats. This bioregulatory preparation stimulated proliferation of mesenchymal stromal cells from deciduous tooth pulp in vitro, but did not affect the rate of their migration in two-dimensional cultures. In vivo experiments showed that application of this preparation in combination with hydroxyapatite and chitosan gel accelerated bone tissue regeneration, thus ensuring restoration of morphologically normal bone matrix. Thus, cattle blood serum is an available source for the production of bioregulatory preparations for medical purposes.

[The efficacy of electroodontodiagnosis by means of various types of current]. / Éffektivnost' élektroodontodiagnostiki s pomoshch'iu razlichnykh vidov toka.

THE PURPOSE OF THE STUDY: determination of the optimal parameters of the action of various types of current, which have the most pronounced irritating effect on the receptor apparatus of the tooth pulp. The study involved 102 volunteers aged 19 to 72 years (53 females and 49 males). The study was conducted on 217 teeth: 86 molars, 25 premolars, 19 canines and 98 incisors. 137 (63%) teeth were intact, in 48 (22%) teeth caries were found, in 32 (15%) teeth there was pulpitis or teeth were depulpated. Electroexcitability of the teeth was determined with the help of various types of electric current: an impulse variable, an impulse constant and a sinusoidal variable. The optimal current for carrying out an electroodontodiagnosis proved to be sinusoidal variable current with a frequency of 50 Hz. This current does not cause polarization of tissues, it is easy to dose, it causes a clear, but not painful sensation, gives the smallest spread of the indicators during repeated studies. The obtained results allowed formulating requirements for electroodontodiagnosis devices.

Pulp sensibility and vitality tests for diagnosing pulpal health in permanent teeth: a critical review.

The aim of this review was to critically appraise the literature related to pulp vitality and sensibility testing in order to determine the diagnostic accuracy of pulp tests with reference to a gold standard or control group. Implications of the results for research and clinical practice are also explored. The MEDLINE (Ovid), MEDLINE (PubMed), Embase and Cochrane databases were searched for English-language clinical trials in humans in which in vivo studies were designed to evaluate or compare the accuracy of selected pulp sensibility and pulp vitality tests in determining the state of pulpal health in permanent teeth. Studies were included only if the results were compared to a control group or to a valid gold or reference standard. Eight studies were identified. Shortcomings in research design were found to influence the findings. The limited number of studies investigating pulp vitality tests was insufficient to answer the research question. It was concluded from this critical appraisal of the literature that laser Doppler flowmetry appeared to be the most accurate method for diagnosing the state of pulpal health and came closest to serving as a gold standard. Pulp vitality tests proved superior to pulp sensibility tests for early and accurate assessments of the pulpal health of traumatized teeth. When accurately used and interpreted, pulp sensibility tests provide valuable diagnostic information, particularly when an electric pulp test is used in combination with either CO2 snow or Endo-Ice.

[Regeneration of dental pulp tissue using pulpal autologous mesenchymal stem cells and platelet-rich plasma]. / Regeneratsiia pul'py zuba s ispol'zovaniem autologichnykh mezenkhimal'nykh stvolovykh kletok pul'py i obogashchennoi trombotsitami plazmy.

Regeneration of pulp and dentin could be important in operative dentistry as a method to save teeth. Currently cell population from dental pulp of deciduous and permanent teeth of humans and laboratory animals are isolated and characterized. The paper presents a study on pulp regeneration using autologous mesenchymal stromal cells from pulp of molars in combination with fibrin clot, transplanted in pulp chamber of miniature pigs after pulp removal. The results proved that transplantation of autologous multipotent stromal cells of dental pulp in combination with autologous platelet-rich plasma in pulp chamber of miniature pigs after pulp removal leads to pulp restoration and reparative dentinogenesis with dentinal bridge formation on the 30th day. However, the completion of regeneration also results in a decrease in the pulp chamber volume due to the neodentin bedding. Tissue regeneration of dental pulp by direct pulp capping in the absence of inflammatory processes is a promising direction of the use of cellular technologies.

SCN2B in the Rat Trigeminal Ganglion and Trigeminal Sensory Nuclei.

The beta-2 subunit of the mammalian brain voltage-gated sodium channel (SCN2B) was examined in the rat trigeminal ganglion (TG) and trigeminal sensory nuclei. In the TG, 42.6 % of sensory neurons were immunoreactive (IR) for SCN2B. These neurons had various cell body sizes. In facial skins and oral mucosae, corpuscular nerve endings contained SCN2B-immunoreactivity. SCN2B-IR nerve fibers formed nerve plexuses beneath taste buds in the tongue and incisive papilla. However, SCN2B-IR free nerve endings were rare in cutaneous and mucosal epithelia. Tooth pulps, muscle spindles and major salivary glands were also innervated by SCN2B-IR nerve fibers. A double immunofluorescence method revealed that about 40 % of SCN2B-IR neurons exhibited calcitonin gene-related peptide (CGRP)-immunoreactivity. However, distributions of SCN2B- and CGRP-IR nerve fibers were mostly different in facial, oral and cranial structures. By retrograde tracing method, 60.4 and 85.3 % of TG neurons innervating the facial skin and tooth pulp, respectively, showed SCN2B-immunoreactivity. CGRP-immunoreactivity was co-localized by about 40 % of SCN2B-IR cutaneous and tooth pulp TG neurons. In trigeminal sensory nuclei of the brainstem, SCN2B-IR neuronal cell bodies were common in deep laminae of the subnucleus caudalis, and the subnuclei interpolaris and oralis. In the mesencephalic trigeminal tract nucleus, primary sensory neurons also exhibited SCN2B-immunoreactivity. In other regions of trigeminal sensory nuclei, SCN2B-IR cells were very infrequent. SCN2B-IR neuropil was detected in deep laminae of the subnucleus caudalis as well as in the subnuclei interpolaris, oralis and principalis. These findings suggest that SCN2B is expressed by various types of sensory neurons in the TG. There appears to be SCN2B-containing pathway in the TG and trigeminal sensory nuclei.

Phenotypes of ATP-activated current associated with their genotypes of P2X1-6 subunits in neurons innervating tooth-pulp.

To explore the association of the phenotype of ATP-activated current with the genotype of P2X1-6 subunits in nociceptors, we developed a method that allows us to label nociceptive neurons innervating tooth-pulp in rat trigeminal ganglion (TG) neurons using a retrograde fluorescence-tracing method, to record ATP-activated current in freshly isolated fluorescence-labeled neurons, and then to conduct single cell immunohistochemical staining for P2X1-6 subunits in the same neuron. We found that fast application of 100 µM ATP to fluorescence-traced TG neurons produced robust inward current in 87% (96/110) of cells tested. The diameter of cells varied from 16 to 56 µm. Three types of ATP-activated current (F, I and S) were recorded with distinct rise times of the current (R10-90, P < 0.05). There was a positive correlation between the cell diameter and the value of R10-90 (P < 0.05): the value of R10-90 increased with increases in the cell diameter. Cells responsive to ATP with the type F current mainly showed positive staining for P2X3 and P2X5, but negative staining for P2X2; cells responsive to ATP with the type I current showed positive staining for P2X1-3 and P2X5, but negative staining for P2X4; and cells responsive to ATP with the type S current showed positive staining for P2X1-5, but negative staining for P2X6. The present findings suggest that in addition to P2X3 subunits, P2X5 subunits are also involved in the generation of the F type of ATP-activated current in small-sized nociceptive neurons. In addition to the P2X2/3 subunit-containing channels, more complex uncharacterized combinations of P2X1-5 subunits exist in native medium-sized nociceptive neurons exhibiting the I and S types of ATP-activated current. In addition, the P2X6 subunit is not a main subunit involved in the nociceptive signal in rat TG neurons innervating tooth-pulp.

Pulp Vitality Preservation of an Involved Tooth in a Large Radicular Cyst: A Case Report with 4-Year Recall.

The current case study presents the surgical endodontic retreatment of a central incisor with a large periapical cyst that had extended to the adjacent lateral incisor. After anaesthesia, a full mucoperiosteal flap was carefully incised and completely reflected. Then, the cyst was cautiously excised without performing curettage of the apical region of the adjacent tooth. A 3-mm deep root-end cavity on tooth #21 was prepared, filled and sealed with calcium-enriched mixture cement. At 6-month and 4-year follow-ups, tooth #21 was fully functional and exhibited no clinical signs/symptoms, and complete periapical healing was evident. This report indicates the importance of proper diagnosis as well as a careful surgical approach in the successful management of comparable cases without the overtreatment of involved teeth.

Comparison of pulse oximeter, cold test, and electric pulp test for assessment of pulp vitality in permanent immature teeth.

INTRODUCTION: Pulp sensitivity tests are commonly used for assessment of pulp vitality. However, indirect assessment of pulp vitality by evaluation of nerve response and subjective nature are the main limitations of these tests. Pulse oximetry is used for assessment of blood oxygen saturation in medicine, and its efficacy for assessment of pulp vitality needs to be evaluated.

Age Differences in Naloxone Reversibility of Electroacupuncture on the Jaw Opening Reflex in Rats.

Background: Electroacupuncture is one of the most popular physical treatments for clinical pain, but the potential influence of a patient's age on the effectiveness of electroacupuncture treatment has not been clearly established. Objectives: The present study aimed to detect a potential difference in electroacupuncture- induced analgesia between juvenile and adult rats. Methods: In this study, we investigated the effects of electroacupuncture treatment on the nociceptive jaw-opening reflex evoked by tooth-pulp stimulation in juvenile and adult rats. Results: Our results showed there were age differences in electroacupuncture-induced analgesic effects in rats, especially with naloxone antagonization. The ratio of naloxonereversibility against electroacupuncture analgesia was greater in adult rats than in juvenile rats. Conclusion: These results suggest that electroacupuncture analgesia is produced mainly by the non-opioid system in juvenile rats and by the opioid system in adult rats.

Toll-Like Receptor 4 in the Rat Caudal Medulla Mediates Tooth Pulp Inflammatory Pain.

The aims of this study were to investigate if Toll-like receptor 4 (TLR4) is expressed in the medullary dorsal horn (MDH) and if medullary application of a TLR4 antagonist (lipopolysaccharides from Rhodobacter sphaeroides, LPS-RS) can attenuate changes in nociceptive sensorimotor responses or TLR4 expression that might be evoked by mustard oil (MO) application to the right maxillary first molar tooth pulp. Of 41 adult male Sprague-Dawley rats used in the study, 23 received intrathecal application of the TLR4 antagonist LPS-RS (25 µg/10 µl; LPS-RS group) or isotonic saline (10 µl; vehicle control group) 10 min before pulpal application of MO (95%; 0.2 µl). Bilateral electromyographic (EMG) activities of the anterior digastric and masseter muscles were recorded continuously before and until 15 min after the MO application to the pulp. In 6 of these 23 rats and an additional 18 rats, the caudal medulla containing the ipsilateral and contralateral MDH was removed after euthanasia for subsequent Western Blot analysis of TLR4 expression in LPS-RS (n = 8) and vehicle (n = 8) groups and a naïve group (n = 8). The % change from baseline in the MO-evoked EMG activities within the anterior digastric muscles were significantly smaller in the LPS-RS group than the control group (two-way ANOVA, post hoc Bonferroni, P < 0.0001). Western Blot analysis revealed similar levels of TLR4 expression in the caudal medulla of the naïve, vehicle and LPS-RS groups. These novel findings suggest that TLR4 signaling in the caudal medulla may mediate MO-induced acute dental inflammatory pain in rats.

CBCT image based segmentation method for tooth pulp cavity region extraction.

OBJECTIVES:: A method was proposed to segment the tooth pulp cavity region in cone beam CT) images, which aimed to make the extraction process more efficient and generate more reliable results for further research. METHODS:: Cone beam CT images of 50 teeth from 10 patients were randomly collected with the help of Peking University Hospital of Stomatology. All slice images have a ground truth tooth pulp cavity region delineated by two doctors manually. After necessary gamma transform in pre-processing stage, three kinds of information in an image such as greyscale, neighbour average greyscale and gradient were fused to search an optimal segmentation threshold by using plane intercept histogram of reciprocal cross entropy algorithm. With the optimal threshold, binarization was conducted and the tooth pulp cavity regions in slice images can be extracted. Qualitative and quantitative analyses compared to ground truth are involved with the evaluation criterion of average non-coincidence rate ( RANOA ). Independent repeated experiments were carried out to test the stability of this segmentation method. RESULTS:: Accurate and complete segmentation results are obtained. The proposed method reaches the lowest RANOA values in most cases and owns more competitive robustness under various interferences compared with the other popular segmentation methods like reciprocal cross entropy method, active contour-based method, region growing method and level set method. Quantitative analysis verified the effectiveness of this method. CONCLUSIONS:: The proposed method can extract tooth pulp cavity regions from teeth efficiently. The segmentation results of this method are more accurate compared to other popular methods under different circumstances and can be used for subsequent applications.

Regulation of CCl4-induced liver cirrhosis by hepatically differentiated human dental pulp stem cells.

Liver transplantation is the most effective treatment for treating liver cirrhosis. However, a limited number of donors, graft rejection, and other complications can undermine transplant success. It is considered that cell transplantation is an alternative approach of liver transplantation. We previously developed a protocol for hepatic differentiation of cluster of differentiation 117+ stem cells isolated from human exfoliated deciduous tooth pulp (SHEDs) under hydrogen sulfide exposure. These cells showed excellent hepatic function. Here, we investigated whether hepatocyte-like cell transplantation is effective for treating carbon tetrachloride (CCl4)-induced liver cirrhosis. SHEDs were hepatically differentiated, which was confirmed via immunological analyses and albumin concentration determination in the medium. Rats were intraperitoneally injected with CCl4 for and the differentiated cells were injected into rat spleen. Histopathological and immunohistochemical analyses were performed. Liver functions were serologically and pathologically determined. Quantitative real-time-polymerase chain reaction was implemented to clarify the treatment procedure of liver cirrhosis. In vitro-differentiated hepatocyte-like cells were positive for all examined hepatic markers. SHED-derived hepatocyte transplantation eliminated liver fibrosis and restored liver structure in rats. Liver immunohistochemical analyses showed the presence of human-specific hepatic markers, i.e., a large amount of human hepatic cells were very active in the liver and spleen. Serological tests revealed significant liver function recovery in the transplantation group. Expression of genes promoting fibrosis increased after cirrhosis induction but was suppressed after transplantation. Our results suggest that xenotransplantation of hepatocyte-like cells of human origin can treat cirrhosis. Moreover, cell-based therapy of chronic liver conditions may be an effective option.