Because of their strong proliferative capacity and multi-potency, placenta-derived mesenchymal stem cells have gained interest as a cell source in the field of nerve damage repair. In the present study, human placenta...Because of their strong proliferative capacity and multi-potency, placenta-derived mesenchymal stem cells have gained interest as a cell source in the field of nerve damage repair. In the present study, human placenta-derived mesenchymal stem ceils were induced to differentiate into neural stem cells, which were then transplanted into the spinal cord after local spinal cord injury in rats. The motor functional recovery and pathological changes in the injured spinal cord were observed for 3 successive weeks. The results showed that human placenta-derived mesenchymal stem cells can differentiate into neuron-like cells and that induced neural stem cells contribute to the restoration of injured spinal cord without causing transplant rejection. Thus, these cells promote the recovery of motor and sensory functions in a rat model of spinal cord injury. Therefore, human placenta-derived mesenchymal stem cells may be useful as seed cells during the repair of spinal cord injury.展开更多
Combined radiation-wound injury(CRWI) is characterized by blood vessel damage and pro-inflammatory cytokine deficiency. Studies have identified that the direct application of leptin plays a significant role in angioge...Combined radiation-wound injury(CRWI) is characterized by blood vessel damage and pro-inflammatory cytokine deficiency. Studies have identified that the direct application of leptin plays a significant role in angiogenesis and inflammation. We established a sustained and stable leptin expression system to study the mechanism. A lentivirus method was employed to explore the angiogenic potential and peripheral inflammation of irradiated human umbilical vein endothelial cells(HUVECs). Leptin was transfected into human placenta-derived mesenchymal stem cells(HPMSCs) with lentiviral vectors. HUVECs were irradiated by X-ray at a single dose of 20 Gy. Transwell migration assay was performed to assess the migration of irradiated HUVECs. Based on the Transwell systems, co-culture systems of HPMSCs and irradiated HUVECs were established. Cell proliferation was measured by cell counting kit-8(CCK-8) assay. The secretion of pro-inflammatory cytokines(human granulocyte macrophage-colony stimulating factor(GM-CSF), interleukin(IL)-1α, IL-6, and IL-8) was detected by enzyme-linked immunosorbent assay(ELISA). The expression of pro-angiogenic factors(vascular endothelial growth factor(VEGF) and basic fibroblast growth factor(b FGF)) mRNA was detected by real-time quantitative polymerase chain reaction(RT-qPCR) assay. Relevant molecules of the nuclear factor-κB(NF-κB) and Janus kinase(JAK)/signal transducer and activator of transcription(STAT) signaling pathways were detected by western blot assay. Results showed that leptin-modified HPMSCs(HPMSCs/leptin) exhibited better cell proliferation, migration, and angiogenic potential(expressed more VEGF and bFGF). In both the single HPMSCs/leptin and the co-culture systems of HPMSCs/leptin and irradiated HUVECs, the increased secretion of pro-inflammatory cytokines(human GM-CSF, IL-1α, and IL-6) was associated with the interaction of the NF-κB and JAK/STAT signaling pathways. We conclude that HPMSCs/leptin could promote angiogenic potential and peripheral inflammation of HUVECs after X-ray radiation.展开更多
We induced human placenta-derived mesenchymal stem cells (hPMSCs) to differentiate into neural cells by adding chemical reagents, despite the fact that toxic chemicals induce cell shrinkage or cytoskeletal formation...We induced human placenta-derived mesenchymal stem cells (hPMSCs) to differentiate into neural cells by adding chemical reagents, despite the fact that toxic chemicals induce cell shrinkage or cytoskeletal formation, which does not represent a proper cell differentiation process. The present study established a co-culture system with hPMSCs and neural cells and analyzed the influence of neural cells on hPMSC differentiation in a co-culture system, hPMSCs were isolated and purified from human full-term placenta using collagenase digestion. Fetal neural cells were co-cultured with hPMSCs for 48 hours using the Transwell co-culture system, hPMSCs co-cultured with neural cells exhibited a slender morphology with a filament. After 96 hours, hPMSCs expressed neuron-specific enolase, which suggested that co-culture of hPMSCs and neural cells induced neural differentiation of hPMSCs.展开更多
Uric acid is an important, naturally occurring serum antioxidant. The present study investigates the use of uric acid for promoting proliferation and neuronal differentiation of mesenchymal stem cells derived from hum...Uric acid is an important, naturally occurring serum antioxidant. The present study investigates the use of uric acid for promoting proliferation and neuronal differentiation of mesenchymal stem cells derived from human placenta tissue. Human placenta-derived mesenchymal stem cells were pre-induced in the presence of either 0, 0.2, 0.4 or 0.8 mM uric acid in combination with 1 mM β-mercaptoethanol for 24 hours, followed by exposure to identical uric acid concentrations and 5 mM β-mercaptoethanol for 6 and 10 hours. Cells developed a neuronal-like morphology, with formation of interconnected process extensions, typical of neural cells. Immunocytochemistry and immunofluorescence staining showed neuron specific enolase positive cells were present in each group except the control group. A greater number of neuron specific enolase positive cells were observed in 0.8 mM uric acid in combination with 5 mM β-mercaptoethanol at 10 hours. After 24 hours of induction, Nissl bodies were detected in the cytoplasm of all differentiated cell groups except the control group and Nissl body numbers were greatest in human placenta-derived mesenchymal stem cells grown in the presence of 0.8 mM uric acid and 5 mM β-mercaptoethanol. These results suggest uric acid accelerates differentiation of human placenta-derived mesenchymal stem cells into neuronal-like cells in a time-and concentration-dependent manner.展开更多
BACKGROUND The effect of hypoxia on mesenchymal stem cells(MSCs)is an emerging topic in MSC biology.Although long non-coding RNAs(lncRNAs)and messenger RNAs(mRNAs)are reported to play a critical role in regulating the...BACKGROUND The effect of hypoxia on mesenchymal stem cells(MSCs)is an emerging topic in MSC biology.Although long non-coding RNAs(lncRNAs)and messenger RNAs(mRNAs)are reported to play a critical role in regulating the biological characteristics of MSCs,their specific expression and co-expression profiles in human placenta-derived MSCs(hP-MSCs)under hypoxia and the underlying mechanisms of lncRNAs in hP-MSC biology are unknown.AIM To reveal the specific expression profiles of lncRNAs in hP-MSCs under hypoxia and initially explored the possible mechanism of lncRNAs on hP-MSC biology.METHODS Here,we used a multigas incubator(92.5%N_(2),5%CO_(2),and 2.5%O_(2))to mimic the potential of hP-MSCs.RNA sequencing technology was applied to identify the exact expression profiles of lncRNAs and mRNAs under hypoxia.RESULTS We identified 289 differentially expressed lncRNAs and 240 differentially expressed mRNAs between the hypoxia and normoxia groups.Among them,the lncRNA SNHG16 was upregulated under hypoxia,which was also validated by reverse transcription-polymerase chain reaction.SNHG16 was confirmed to affect hP-MSC proliferation rates using a SNHG16 knockdown model.SNHG16 overexpression could significantly enhance the proliferation capacity of hP-MSCs,activate the PI3K/AKT pathway,and upregulate the expression of cell cycle-related proteins.CONCLUSION Our results revealed the specific expression characteristics of lncRNAs and mRNAs in hypoxiacultured hP-MSCs and that lncRNA SNHG16 can promote hP-MSC proliferation through the PI3K/AKT pathway.展开更多
Mesenchymal stem cells(MSCs)capable of tumour topotaxis have been served as cellular vehicles to deliver anti-tumour agents.As cellular components of the tumour microenvironment,MSCs also affect tumour progression.How...Mesenchymal stem cells(MSCs)capable of tumour topotaxis have been served as cellular vehicles to deliver anti-tumour agents.As cellular components of the tumour microenvironment,MSCs also affect tumour progression.However,the tumour transformation-related genes of MSCs remain unclear since either tumorigenic or tumour suppressor effects within these cells have been researched.Hence,we aimed to identify potential biomarkers indicative of tumorigenic risk by RNA-seq analysis of human placenta tissue-derived MSCs(hPTMSCs)exposed to the carcinogenic agent,3-methylcholanthrene(3-MC).Twenty-nine tumour transformation-related genes and three pluripotency-related genes were appraised as differentially expressed genes(DEGs)in hPTMSCs.Overexpression of sfrp1 led to reduced cell viability,migration,and colony formation in A549.In contrast,the overexpression of ptgs2 exerted the opposite effect.These results indicate that A549 cells with high ptgs2 expression but low sfrp1 expression may have a more potential tumorigenic capacity.Taken together,this study suggests that ptgs2 and sfrp1 may be tumorigenic risk genes.展开更多
Human placenta-derived stem cells (hPDSCs) were isolated by trypsinization and further induced into cartilage cells in vitro.The engineered cartilage was constructed by combining hPDSCs with collagen sponge and the ca...Human placenta-derived stem cells (hPDSCs) were isolated by trypsinization and further induced into cartilage cells in vitro.The engineered cartilage was constructed by combining hPDSCs with collagen sponge and the cartilage formation was observed by implantation into nude mice.Results showed that hPDSCs featured mesenchymal stem cells and maintained proliferation in vitro for over 30 passages while remaining undifferentiated.All results indicated that hPDSCs have the potential to differentiate into functional cartilage cells in vitro when combined with collagen sponge,which provided experimental evidence for prospective clinical application.展开更多
基金supported by a grant from the Scientific Research Program of Liaoning Provincial Science and Technology Ministry in China,No.2012225014
文摘Because of their strong proliferative capacity and multi-potency, placenta-derived mesenchymal stem cells have gained interest as a cell source in the field of nerve damage repair. In the present study, human placenta-derived mesenchymal stem ceils were induced to differentiate into neural stem cells, which were then transplanted into the spinal cord after local spinal cord injury in rats. The motor functional recovery and pathological changes in the injured spinal cord were observed for 3 successive weeks. The results showed that human placenta-derived mesenchymal stem cells can differentiate into neuron-like cells and that induced neural stem cells contribute to the restoration of injured spinal cord without causing transplant rejection. Thus, these cells promote the recovery of motor and sensory functions in a rat model of spinal cord injury. Therefore, human placenta-derived mesenchymal stem cells may be useful as seed cells during the repair of spinal cord injury.
基金Project supported by the Special Fund for Cooperation of Local Government and College(Schools and Institutes)in Changchun,Jilin Province(No.17DY024),China。
文摘Combined radiation-wound injury(CRWI) is characterized by blood vessel damage and pro-inflammatory cytokine deficiency. Studies have identified that the direct application of leptin plays a significant role in angiogenesis and inflammation. We established a sustained and stable leptin expression system to study the mechanism. A lentivirus method was employed to explore the angiogenic potential and peripheral inflammation of irradiated human umbilical vein endothelial cells(HUVECs). Leptin was transfected into human placenta-derived mesenchymal stem cells(HPMSCs) with lentiviral vectors. HUVECs were irradiated by X-ray at a single dose of 20 Gy. Transwell migration assay was performed to assess the migration of irradiated HUVECs. Based on the Transwell systems, co-culture systems of HPMSCs and irradiated HUVECs were established. Cell proliferation was measured by cell counting kit-8(CCK-8) assay. The secretion of pro-inflammatory cytokines(human granulocyte macrophage-colony stimulating factor(GM-CSF), interleukin(IL)-1α, IL-6, and IL-8) was detected by enzyme-linked immunosorbent assay(ELISA). The expression of pro-angiogenic factors(vascular endothelial growth factor(VEGF) and basic fibroblast growth factor(b FGF)) mRNA was detected by real-time quantitative polymerase chain reaction(RT-qPCR) assay. Relevant molecules of the nuclear factor-κB(NF-κB) and Janus kinase(JAK)/signal transducer and activator of transcription(STAT) signaling pathways were detected by western blot assay. Results showed that leptin-modified HPMSCs(HPMSCs/leptin) exhibited better cell proliferation, migration, and angiogenic potential(expressed more VEGF and bFGF). In both the single HPMSCs/leptin and the co-culture systems of HPMSCs/leptin and irradiated HUVECs, the increased secretion of pro-inflammatory cytokines(human GM-CSF, IL-1α, and IL-6) was associated with the interaction of the NF-κB and JAK/STAT signaling pathways. We conclude that HPMSCs/leptin could promote angiogenic potential and peripheral inflammation of HUVECs after X-ray radiation.
文摘We induced human placenta-derived mesenchymal stem cells (hPMSCs) to differentiate into neural cells by adding chemical reagents, despite the fact that toxic chemicals induce cell shrinkage or cytoskeletal formation, which does not represent a proper cell differentiation process. The present study established a co-culture system with hPMSCs and neural cells and analyzed the influence of neural cells on hPMSC differentiation in a co-culture system, hPMSCs were isolated and purified from human full-term placenta using collagenase digestion. Fetal neural cells were co-cultured with hPMSCs for 48 hours using the Transwell co-culture system, hPMSCs co-cultured with neural cells exhibited a slender morphology with a filament. After 96 hours, hPMSCs expressed neuron-specific enolase, which suggested that co-culture of hPMSCs and neural cells induced neural differentiation of hPMSCs.
文摘Uric acid is an important, naturally occurring serum antioxidant. The present study investigates the use of uric acid for promoting proliferation and neuronal differentiation of mesenchymal stem cells derived from human placenta tissue. Human placenta-derived mesenchymal stem cells were pre-induced in the presence of either 0, 0.2, 0.4 or 0.8 mM uric acid in combination with 1 mM β-mercaptoethanol for 24 hours, followed by exposure to identical uric acid concentrations and 5 mM β-mercaptoethanol for 6 and 10 hours. Cells developed a neuronal-like morphology, with formation of interconnected process extensions, typical of neural cells. Immunocytochemistry and immunofluorescence staining showed neuron specific enolase positive cells were present in each group except the control group. A greater number of neuron specific enolase positive cells were observed in 0.8 mM uric acid in combination with 5 mM β-mercaptoethanol at 10 hours. After 24 hours of induction, Nissl bodies were detected in the cytoplasm of all differentiated cell groups except the control group and Nissl body numbers were greatest in human placenta-derived mesenchymal stem cells grown in the presence of 0.8 mM uric acid and 5 mM β-mercaptoethanol. These results suggest uric acid accelerates differentiation of human placenta-derived mesenchymal stem cells into neuronal-like cells in a time-and concentration-dependent manner.
基金Supported by Stem Cell and Translational Research from National Key Research and Development Program of China,No.2020YFA0113003National Natural Science Foundation of China,No.81971756.
文摘BACKGROUND The effect of hypoxia on mesenchymal stem cells(MSCs)is an emerging topic in MSC biology.Although long non-coding RNAs(lncRNAs)and messenger RNAs(mRNAs)are reported to play a critical role in regulating the biological characteristics of MSCs,their specific expression and co-expression profiles in human placenta-derived MSCs(hP-MSCs)under hypoxia and the underlying mechanisms of lncRNAs in hP-MSC biology are unknown.AIM To reveal the specific expression profiles of lncRNAs in hP-MSCs under hypoxia and initially explored the possible mechanism of lncRNAs on hP-MSC biology.METHODS Here,we used a multigas incubator(92.5%N_(2),5%CO_(2),and 2.5%O_(2))to mimic the potential of hP-MSCs.RNA sequencing technology was applied to identify the exact expression profiles of lncRNAs and mRNAs under hypoxia.RESULTS We identified 289 differentially expressed lncRNAs and 240 differentially expressed mRNAs between the hypoxia and normoxia groups.Among them,the lncRNA SNHG16 was upregulated under hypoxia,which was also validated by reverse transcription-polymerase chain reaction.SNHG16 was confirmed to affect hP-MSC proliferation rates using a SNHG16 knockdown model.SNHG16 overexpression could significantly enhance the proliferation capacity of hP-MSCs,activate the PI3K/AKT pathway,and upregulate the expression of cell cycle-related proteins.CONCLUSION Our results revealed the specific expression characteristics of lncRNAs and mRNAs in hypoxiacultured hP-MSCs and that lncRNA SNHG16 can promote hP-MSC proliferation through the PI3K/AKT pathway.
基金supported by grants from the Ningxia Science and Technological Supporting Project(2015KJHM38)the Ningxia Natural Science Foundation(2019AAC03231).
文摘Mesenchymal stem cells(MSCs)capable of tumour topotaxis have been served as cellular vehicles to deliver anti-tumour agents.As cellular components of the tumour microenvironment,MSCs also affect tumour progression.However,the tumour transformation-related genes of MSCs remain unclear since either tumorigenic or tumour suppressor effects within these cells have been researched.Hence,we aimed to identify potential biomarkers indicative of tumorigenic risk by RNA-seq analysis of human placenta tissue-derived MSCs(hPTMSCs)exposed to the carcinogenic agent,3-methylcholanthrene(3-MC).Twenty-nine tumour transformation-related genes and three pluripotency-related genes were appraised as differentially expressed genes(DEGs)in hPTMSCs.Overexpression of sfrp1 led to reduced cell viability,migration,and colony formation in A549.In contrast,the overexpression of ptgs2 exerted the opposite effect.These results indicate that A549 cells with high ptgs2 expression but low sfrp1 expression may have a more potential tumorigenic capacity.Taken together,this study suggests that ptgs2 and sfrp1 may be tumorigenic risk genes.
文摘Human placenta-derived stem cells (hPDSCs) were isolated by trypsinization and further induced into cartilage cells in vitro.The engineered cartilage was constructed by combining hPDSCs with collagen sponge and the cartilage formation was observed by implantation into nude mice.Results showed that hPDSCs featured mesenchymal stem cells and maintained proliferation in vitro for over 30 passages while remaining undifferentiated.All results indicated that hPDSCs have the potential to differentiate into functional cartilage cells in vitro when combined with collagen sponge,which provided experimental evidence for prospective clinical application.