Bispecific antibody targeting both B7-H3 and PD-L1 exhibits superior antitumor activities.

Clinical application of PD-1 and PD-L1 monoclonal antibodies (mAbs) is hindered by their relatively low response rates and the occurrence of drug resistance. Co-expression of B7-H3 with PD-L1 has been found in various solid tumors, and combination therapies that target both PD-1/PD-L1 and B7-H3 pathways may provide  additional therapeutic benefits. Up to today, however, no bispecific antibodies targeting both PD-1 and B7-H3 have reached the clinical development stage. In this study, we generated a stable B7-H3×PD-L1 bispecific antibody (BsAb) in IgG1-VHH format by coupling a humanized IgG1 mAb against PD-L1 with a humanized camelus variable domain of the heavy-chain of heavy-chain antibody (VHH) against human B7-H3. The BsAb exhibited favorable thermostability, efficient T cell activation, IFN-γ production, and antibody-dependent cell-mediated cytotoxicity (ADCC). In a PBMC humanized A375 xenogeneic tumor model, treatment with BsAb (10 mg/kg, i.p., twice a week for 6 weeks) showed enhanced antitumor activities compared to monotherapies and, to some degree, combination therapies. Our results suggest that targeting both PD-1 and B7-H3 with BsAbs increases their specificities to B7-H3 and PD-L1 double-positive tumors and induces a synergetic effect. We conclude that B7-H3×PD-L1 BsAb is favored over mAbs and possibly combination therapies in treating B7-H3 and PD-L1 double-positive tumors.

Ophiopogon japonicus and its active compounds: A review of potential anticancer effects and underlying mechanisms.

BACKGROUND: Ophiopogon japonicus (Thunb.) Ker Gawl., a well-known Chinese herb, has been used in traditional Chinese medicine for thousands of years. Extensive in vitro and in vivo studies have shown that O. japonicus and its active compounds exhibit potential anticancer effects in a variety of cancer cells in vitro and suppress tumor growth and metastasis without causing serious toxicity in vivo. PURPOSE: This review aims to systemically summarize and discuss the anticancer effects and the underlying mechanisms of O. japonicus extracts and its active compounds. METHODS: The review is prepared following the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Various scientific databases including Web of Science, PubMed, Scopus, and Chinese National Knowledge Infrastructure were searched using the keywords: Ophiopogon japonicus, tumor, cancer, carcinoma, content, pharmacokinetics, and toxicity. RESULTS: O. japonicus extracts and the active compounds, such as ruscogenin-1-O-[ß-d-glucopyranosyl(1→2)][ß-d-xylopyranosyl(1→3)]-ß-d-fucopyranoside (DT-13), ophiopogonin B, and ophiopogonin D, exert potential anticancer effects, including the induction of cell cycle arrest, activation of apoptosis and autophagy, and inhibition of metastasis and angiogenesis. In addition, the mechanisms underlying these effects, as well as the pharmacokinetics, toxicity and clinical utility of O. japonicus extracts and active compounds are discussed. Furthermore, this review highlights the research and application prospects of these compounds in immunotherapy and combination chemotherapy. CONCLUSIONS: The traditional herb O. japonicus and its phytochemicals could be safe and reliable anticancer drug candidates, alone or in combination with chemotherapeutic drugs. We hope that this review, which highlights the anticancer properties of O. japonicus, will contribute to drug optimization, therapeutic development, and future studies on cancer therapies based on this medicinal plant.

Comparison of Ophiopogon japonicus and Liriope spicata var. prolifera from Different Origins Based on Multi-Component Quantification and Anticancer Activity.

The tuberous root of Ophiopogon japonicus (Thunb.) Ker-Gawl. is a well-known Chinese medicine also called Maidong (MD) in Chinese. It could be divided into "Chuanmaidong" (CMD) and "Zhemaidong" (ZMD), according to the geographic origins. Meanwhile, the root of Liriope spicata (Thunb.) Lour. var. prolifera Y. T. Ma (SMD) is occasionally used as a substitute for MD in the market. In this study, a reliable pressurized liquid extraction and HPLC-DAD-ELSD method was developed for the simultaneous determination of nine chemical components, including four steroidal saponins (ophiopojaponin C, ophiopogonin D, liriopesides B and ophiopogonin D'), four homoisoflavonoids (methylophiopogonone A, methylophiopogonone B, methylophiopogonanone A and methylophiopogonanone B) and one sapogenin (ruscogenin) in CMD, ZMD and SMD. The method was validated in terms of linearity, sensitivity, precision, repeatability and accuracy, and then applied to the real samples from different origins. The results indicated that there were significant differences in the contents of the investigated compounds in CMD, ZMD and SMD. Ruscogenin was not detected in all the samples, and liriopesides B was only found in SMD samples. CMD contained higher ophiopogonin D and ophiopogonin D', while the other compounds were more abundant in ZMD. Moreover, the anticancer effects of the herbal extracts and selected components against A2780 human ovarian cancer cells were also compared. CMD and ZMD showed similar cytotoxic effects, which were stronger than those of SMD. The effects of MD may be due to the significant anticancer potential of ophiopognin D' and homoisoflavonoids. These results suggested that there were great differences in the chemical composition and pharmacological activity among CMD, ZMD and SMD; thus, their origins should be carefully considered in clinical application.

Multifunctional Graphene Oxide Nanodelivery Platform for Breast Cancer Treatment.

Background: Breast cancer (BC) has the highest global prevalence among all malignancies in women and the second highest prevalence in the overall population. Paclitaxel (PTX), a tricyclic diterpenoid, is effective against BC. However, its poor solubility in water and the allergenicity of its dissolution medium limited its clinical application. Methods: In this work, we established a multifunctional graphene oxide (GO) tumor-targeting drug delivery system using nanosized graphene oxide (nGO) modified with D-tocopherol polyethylene glycol succinate (TPGS) and arginine-glycine-aspartic acid (RGD) for PTX loading. Results: The obtained RGD-TPGS-nGO-PTX was 310.20±19.86 nm in size; the polydispersity index (PDI) and zeta potential were 0.21±0.020 and -23.42 mV, respectively. The mean drug loading capacity of RGD-TPGS-nGO-PTX was 48.78%. RGD-TPGS-nGO-PTX showed satisfactory biocompatibility and biosafety and had no significant toxic effects on zebrafish embryos. Importantly, it exerted excellent cytotoxicity against MDA-MB-231 cells, reversed multi-drug resistance (MDR) in MCF-7/ADR cells, and showed significant anti-tumor efficacy in tumor-bearing nude mice. Conclusion: These findings strongly suggested that the multifunctional GO tumor-targeting drug delivery system RGD-TPGS-nGO-PTX could be used in clinical settings to improve PTX delivery, reverse MDR and increase the therapeutic efficacy of BC treatment.

Cell metabolomics study on the anticancer effects of Ophiopogon japonicus against lung cancer cells using UHPLC/Q-TOF-MS analysis.

Ophiopogon japonicus (OJ) is a traditional Chinese herbal medicine that has been used for thousands of years. Recently, the anticancer effects of OJ have been reported in multiple types of cancer, particularly in lung cancer. However, the underlying mechanisms remain unclear. In present study, the effects of OJ against NCI-H1299 human lung cancer cells were investigated, and the underlying mechanisms were explored using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC/Q-TOF-MS)-based cell metabolomics. As a result, OJ inhibited the proliferation, induced the apoptosis and suppressed the migration of NCI-H1299 cells. A total of 22 differential metabolites responsible for the effects of OJ were screened and annotated based on the LC-MS-based cell metabolomics approach. The altered metabolites were involved in three metabolic pathways, including glycerophospholipid metabolism, ether lipid metabolism and glutathione metabolism. These results showed that cell metabolomics-based strategies are promising tools to discover the action mechanisms of OJ against lung cancer cells.

The BMSC-derived exosomal lncRNA Mir9-3hg suppresses cardiomyocyte ferroptosis in ischemia-reperfusion mice via the Pum2/PRDX6 axis.

BACKGROUND AND AIMS: The exosomal long noncoding RNAs (lncRNAs) have been reported to have cardioprotective effects on ischemia-reperfusion (I/R) injury by hindering ferroptosis, but the role of lncRNA Mir9-3 host gene (Mir9-3hg) in cardiac I/R injury remains unclear. METHODS AND RESULTS: Exosomes were extracted from mouse bone marrow mesenchymal stem cells (BMSCs) and identified by detecting the exosome specific marker levels, and the results showed that Mir9-3hg was highly expressed in BMSCs-Exo. Hypoxia/reoxygenation (H/R)-treated HL-1 mouse cardiomyocytes were incubated with exosomes extracted from BMSCs transfected with Mir9-3hg siRNA. BMSCs-Exo incubation observably facilitated cell proliferation, increased glutathione (GSH) content, and reduced iron ion concentration, reactive oxygen species (ROS) level and ferroptosis marker protein levels in H/R-treated cells, while interfering Mir9-3hg reversed these effects. RNA binding protein immunoprecipitation assay was found that Mir9-3hg bound with pumilio RNA binding family member 2 (Pum2) protein and downregulated Pum2 expression. Silence of Pum2 reversed the effects of Mir9-3hg inhibition on cell functions. Chromatin immunoprecipitation assay was revealed that Pum2 bound with peroxiredoxin 6 (PRDX6) promoter and restrained PRDX6 expression. Silence of PRDX6 reversed the improved effects of Pum2 downregulation on cell functions. Additionally, BMSCs-Exo treatment ameliorated cardiac function in I/R-treated mice by inhibiting cardiomyocyte ferroptosis. CONCLUSIONS: BMSCs-Exo treatment attenuates I/R-induced cardiac injury by inhibiting cardiomyocyte ferroptosis through modulating the Pum2/PRDX6 axis, thereby ameliorating cardiac function.

Galectin-1 inhibition induces cell apoptosis through dual suppression of CXCR4 and Ras pathways in human malignant peripheral nerve sheath tumors.

BACKGROUND: The Ras signaling pathway is commonly dysregulated in human malignant peripheral nerve sheath tumors (MPNSTs). It is well known that galectin-1 (Gal-1) is essential to stabilize membrane Ras and thereby induce the activation of Ras. However, the role of Gal-1 in MPNST progression remains unknown. The aim of this study was to examine whether Gal-1 knockdown could have an effect on the Ras signaling pathway. METHODS: Cell viability, apoptosis assay, and colony formation were performed to examine the effects of inhibition of Gal-1 in MPNST cells. We used a human MPNST xenograft model to assess growth and metastasis inhibitory effects of Gal-1 inhibitor LLS2. RESULTS: Gal-1 was upregulated in MPNST patients and was highly expressed in MPNST cells. Knockdown of Gal-1 by small interfering (si)RNA in Gal-1 expressing MPNST cells significantly reduces cell proliferation through the suppression of C-X-C chemokine receptor type 4 (CXCR4) and the rat sarcoma viral oncogene homolog (RAS)/extracellular signal-regulated kinase (ERK) pathway, which are important oncogenic signaling in MPNST development. Moreover, Gal-1 knockdown induces apoptosis and inhibits colony formation. LLS2, a novel Gal-1 allosteric small molecule inhibitor, is cytotoxic against MPNST cells and was able to induce apoptosis and suppress colony formation in MPNST cells. LLS2 treatment and Gal-1 knockdown exhibited similar effects on the suppression of CXCR4 and RAS/ERK pathways. More importantly, inhibition of Gal-1 expression or function by treatment with either siRNA or LLS2 resulted in significant tumor responses in an MPNST xenograft model. CONCLUSION: Our results identified an oncogenic role of Gal-1 in MPNST and that its inhibitor, LLS2, is a potential therapeutic agent, applied topically or systemically, against MPNST.

Superconductivity in solid benzene molecular crystal.

Light-element compounds hold great promise of high critical temperature superconductivity judging from the theoretical perspective. A hydrogen-rich material, benzene, is such a kind of candidate but also an organic compound. A series of first-principles calculations are performed on the electronic structures, dynamics properties, and electron-phonon interactions of solid benzene at high pressures. Benzene is found to be dynamically stable in the pressure range of 180-200 GPa and to exhibit superconductivity with a maximum transition temperature of 20 K at 195 GPa. The phonon modes of carbon atoms are identified to mainly contribute to the electron-phonon interactions driving this superconductivity. The predicted superconductivity in this simplest pristine hydrocarbon shows a common feature in aromatic hydrocarbons and also makes it a bridge to organic and hydrogen-rich superconductors.

Targeting Galectin-1 Impairs Castration-Resistant Prostate Cancer Progression and Invasion.

Purpose: The majority of patients with prostate cancer who are treated with androgen-deprivation therapy (ADT) will eventually develop fatal metastatic castration-resistant prostate cancer (mCRPC). Currently, there are no effective durable therapies for patients with mCRPC. High expression of galectin-1 (Gal-1) is associated with prostate cancer progression and poor clinical outcome. The role of Gal-1 in tumor progression is largely unknown. Here, we characterized Gal-1 functions and evaluated the therapeutic effects of a newly developed Gal-1 inhibitor, LLS30, in mCRPC.Experimental Design: Cell viability, colony formation, migration, and invasion assays were performed to examine the effects of inhibition of Gal-1 in CRPC cells. We used two human CRPC xenograft models to assess growth-inhibitory effects of LLS30. Genome-wide gene expression analysis was conducted to elucidate the effects of LLS30 on metastatic PC3 cells.Results: Gal-1 was highly expressed in CRPC cells, but not in androgen-sensitive cells. Gal-1 knockdown significantly inhibited CRPC cells' growth, anchorage-independent growth, migration, and invasion through the suppression of androgen receptor (AR) and Akt signaling. LLS30 targets Gal-1 as an allosteric inhibitor and decreases Gal-1-binding affinity to its binding partners. LLS30 showed in vivo efficacy in both AR-positive and AR-negative xenograft models. LLS30 not only can potentiate the antitumor effect of docetaxel to cause complete regression of tumors, but can also effectively inhibit the invasion and metastasis of prostate cancer cells in vivoConclusions: Our study provides evidence that Gal-1 is an important target for mCRPC therapy, and LLS30 is a promising small-molecule compound that can potentially overcome mCRPC. Clin Cancer Res; 24(17); 4319-31. ©2018 AACR.

Cetuximab conjugated and doxorubicin loaded silica nanoparticles for tumor-targeting and tumor microenvironment responsive binary drug delivery of liver cancer therapy.

In the present study, we successfully developed a preferable doxorubicin (Dox) loaded drug delivery system based on Cetuximab and silica nanoparticles (Cet-SLN/Dox). By employing the tumor homing property of Cetuximab and the drug-loading capability of silica nanoparticles, the prepared Cet-SLN/Dox was able to load Dox to achieve the co-delivery of two drugs (Cetuximab and Dox). In vitro analysis revealed that Cet-SLN/Dox was nano-sized particles with decent drug loading capabilities and smart drug release profile. Further studies demonstrated that Cet-SLN/Dox was superior in tumor-homing and anti-cancer efficiency than Cetuximab free SLN/Dox and free Dox, possibly due to EGFR mediated endocytosis and the combined anti-cancer effects of Cetuximab and Dox within Cet-SLN/Dox.

Saponins from Chinese Medicines as Anticancer Agents.

Saponins are glycosides with triterpenoid or spirostane aglycones that demonstrate various pharmacological effects against mammalian diseases. To promote the research and development of anticancer agents from saponins, this review focuses on the anticancer properties of several typical naturally derived triterpenoid saponins (ginsenosides and saikosaponins) and steroid saponins (dioscin, polyphyllin, and timosaponin) isolated from Chinese medicines. These saponins exhibit in vitro and in vivo anticancer effects, such as anti-proliferation, anti-metastasis, anti-angiogenesis, anti-multidrug resistance, and autophagy regulation actions. In addition, related signaling pathways and target proteins involved in the anticancer effects of saponins are also summarized in this work.

Anticancer Activities of Protopanaxadiol- and Protopanaxatriol-Type Ginsenosides and Their Metabolites.

Recently, most anticancer drugs are derived from natural resources such as marine, microbial, and botanical sources, but the low success rates of chemotherapies and the development of multidrug resistance emphasize the importance of discovering new compounds that are both safe and effective against cancer. Ginseng types, including Asian ginseng, American ginseng, and notoginseng, have been used traditionally to treat various diseases, due to their immunomodulatory, neuroprotective, antioxidative, and antitumor activities. Accumulating reports have shown that ginsenosides, the major active component of ginseng, were helpful for tumor treatment. 20(S)-Protopanaxadiol (PDS) and 20(S)-protopanaxatriol saponins (PTS) are two characteristic types of triterpenoid saponins in ginsenosides. PTS holds capacity to interfere with crucial metabolism, while PDS could affect cell cycle distribution and prodeath signaling. This review aims at providing an overview of PTS and PDS, as well as their metabolites, regarding their different anticancer effects with the proposal that these compounds might be potent additions to the current chemotherapeutic strategy against cancer.

Phytochemistry and Pharmacology of Carthamus tinctorius L.

Carthamus tinctorius L. is a multifunctional cash crop. Its flowers and seeds are extensively used in traditional herbal medicine in China, Korea, Japan, and other Asian countries, for treating various ailments such as gynecological, cardiovascular, and cerebrovascular diseases as well as blood stasis and osteoporosis. More than 100 compounds have been isolated and identified from C. tinctorius. Flavonoids and alkaloids, especially the quinochalcone c-glycoside hydroxysafflor yellow A, N-(p-Coumaroyl)serotonin, and N-feruloylserotonin, are responsible for most of the pharmacological activities of C. tinctorius. In this paper, comprehensive and up-to-date information on the phytochemistry and pharmacology of C. tinctorius is presented. This information will be helpful for further explorations of the therapeutic potential of C. tinctorius and may provide future research opportunities.

Ophiopogon japonicus--A phytochemical, ethnomedicinal and pharmacological review.

ETHNOPHARMACOLOGICAL RELEVANCE: Ophiopogonis Radix (Maidong in Chinese), the root of Ophiopogon japonicus, is widely used in local medicines of China, Japan and some south-eastern Asian countries. According to the traditional Chinese medicine (TCM) principle, Ophiopogonis Radix nourishes the yin, promotes body fluid production, moistens the lung, eases the mind and clears away heart fire. This review summarizes the achievements of the investigations in botany, phytochemistry, quality control, traditional uses, pharmacological activities and clinical studies on O. japonicus; this review also describes the shortcomings of studies on this herbal drug and thus serves as the basis of further scientific research and development of this traditional herbal drug. MATERIALS AND METHODS: O. japonicus-related information was collected from various resources, including books on Chinese herbs and the Internet databases, such as Google Scholar, SciFinder, Web of Science, Elsevier, ACS, PubMed and China Knowledge Resource Integrated (CNKI). RESULTS: O. japonicus is widely distributed in East Asia, especially in China. Numerous compounds were identified from this plant. The main components of O. japonicus include steroidal saponins, homoisoflavonoids and polysaccharides, which exhibited various pharmacological activities, such as cardiovascular protection, anti-inflammation, anticancer, anti-oxidation, immunomodulation, cough relief, antimicrobial, and anti-diabetes. CONCLUSIONS: O. japonicus is a common traditional Chinese herbal drug used as the main ingredient in many prescriptions. Modern researches verified that O. japonicus can be used either as a healthy food or a therapeutic agent for disease prevention and treatment. The molecular mechanisms and chemical principles of this herbal medicine should be further explored.

A Systematic Review of the Anticancer Properties of Compounds Isolated from Licorice (Gancao).

Licorice (Gancao in Chinese) has been used worldwide as a botanical source in medicine and as a sweetening agent in food products for thousands of years. Triterpene saponins and flavonoids are its main ingredients that exhibit a variety of biological activities, including hepatoprotective, antiulcer, anti-inflammatory, antiviral and anticancer effects among others. This review attempts to summarize the current knowledge on the anticancer properties and mechanisms of the compounds isolated from licorice and obtain new insights for further research and development of licorice. A broad spectrum of in vitro and in vivo studies have recently demonstrated that the mixed extracts and purified compounds from licorice exhibit evident anticancer properties by inhibition of proliferation, induction of cell cycle arrest, apoptosis, autophagy, differentiation, suppression of metastasis, angiogenesis, and sensitization of chemotherapy or radiotherapy. A combined treatment of licorice compounds and clinical chemotherapy drugs remarkably enhances anticancer effects and reduces the side effects of chemotherapeutics. Furthermore, glycyrrhizic acid and glycyrrhetinic acid in licorice have been indicated to present obvious liver-targeting effects in targeted drug delivery systems for hepatocellular carcinoma treatment.

Chemical Constituents, Quality Control, and Bioactivity of Epimedii Folium (Yinyanghuo).

Epimedii Folium (Yinyanghuo in Chinese) is one of the most commonly used traditional Chinese medicines. Its main active components are flavonoids, which exhibit multiple biological activities, such as promotion of bone formation and sexual function, protection of the nervous system, and prevention of cardiovascular diseases. Flavonoids also show anti-inflammatory and anticancer effects. Various effective methods, including genetic and chemical approaches, have been developed for the quality control of Yinyanghuo. In this review, the studies conducted in the last decade about the chemical constituents, quality control, and bioactivity of Yinyanghuo are summarized and discussed.

Pressure-driven quantum criticality in iron-selenide superconductors.

We report a finding of a pressure-induced quantum critical transition in K0.8Fe(x)Se2 (x = 1.7 and 1.78) superconductors through in situ high-pressure electrical transport and x-ray diffraction measurements in diamond anvil cells. Transitions from metallic Fermi liquid behavior to non-Fermi liquid behavior and from antiferromagnetism to paramagnetism are found in the pressure range of 9.2-10.3 GPa, in which superconductivity tends to disappear. The change around the quantum critical point from the coexisting antiferromagnetism state and the Fermi liquid behavior to the paramagnetism state and the non-Fermi liquid behavior in the iron-selenide superconductors demonstrates a unique mechanism for their quantum critical transition.

Re-emerging superconductivity at 48 kelvin in iron chalcogenides.

Pressure has an essential role in the production and control of superconductivity in iron-based superconductors. Substitution of a large cation by a smaller rare-earth ion to simulate the pressure effect has raised the superconducting transition temperature T(c) to a record high of 55 K in these materials. In the same way as T(c) exhibits a bell-shaped curve of dependence on chemical doping, pressure-tuned T(c) typically drops monotonically after passing the optimal pressure. Here we report that in the superconducting iron chalcogenides, a second superconducting phase suddenly re-emerges above 11.5 GPa, after the T(c) drops from the first maximum of 32 K at 1 GPa. The T(c) of the re-emerging superconducting phase is considerably higher than the first maximum, reaching 48.0-48.7 K for Tl(0.6)Rb(0.4)Fe(1.67)Se(2), K(0.8)Fe(1.7)Se(2) and K(0.8)Fe(1.78)Se(2).

Sodium selenite-induced apoptosis mediated by ROS attack in human osteosarcoma U2OS cells.

Sodium selenite (Na(2)SeO(3), SSE) is an inorganic Se compound that is widely used in cancer chemoprevention studies. SSE has been shown to have anti-proliferative effects on several types of human cancer cells, but its effect on osteosarcoma cells has thus far not been reported. In this study, the cytotoxic effect of SSE on osteosarcoma cells U2OS was investigated in vitro and found to be higher than on comparable non-cancer cell lines 293 and L6. Treatment with SSE decreased cell growth in a dose- and time-dependent manner and altered cellular morphology. SSE also inhibited cell viability by inducing apoptosis, as evidenced by the formation of apoptotic bodies, generation of reactive oxygen species (ROS), and accumulation of cells during the advanced phase of apoptosis. SSE-induced apoptosis correlated with the activation of CASP 3, downregulation of BCL-2, and upregulation of P53 and PTEN in U2OS cells. These results indicated that SSE induces apoptosis in U2OS cells mainly through an ROS-mediated caspase pathway. This is the first report to show a possible mechanism of the anti-proliferative effect of SSE for the prevention of osteosarcoma in cell culture models.

Differentiation of human umbilical cord mesenchymal stem cells into hepatocyte-like cells by hTERT gene transfection in vitro.

The availability of a large quantity of MSCs (mesenchymal stem cells) would greatly advance liver-directed cell therapies. However, MSCs have a limited lifespan in vitro. Therefore we tested whether hUCMSCs (human umbilical cord MSCs) could be immortalized by transduction with a lentiviral vector carrying the hTERT (human telomerase reverse transcriptase) catalytic subunit gene, and investigated their differentiation potential. Transfected hUCMSCs overexpressed the hTERT gene and up-regulated their telomerase activity. The transfected hUCMSCs maintained their typical morphology and MSC-specific markers, and vigorously proliferated, undergoing more than 100 PDs (population doublings) to date. Following incubation with hepatogenic agents, the transfected hUCMSCs differentiated into hepatocyte-like cells, and expressed hepatic markers, such as albumin, AFP (α-fetoprotein) and CK-18 (cytokeratin-18). Transfected hUCMSCs showed no transformation into tumours in nude mice. In conclusion, telomerization of hUCMSCs by hTERT overexpression extends their replicative lifespan without influencing their hepatogenic differentiation potential. This offers opportunities for obtaining sufficient quantities of cells for liver-directed therapies.