Missing value imputation (MVI) is important for DNA microarray data analysis because microarray data with missing values would significantly degrade the performance of the downstream analysis. ...Although there have been lots of MVI algorithms for dealing with the missing DNA microarray data, we note that most of them have a lack of robustness owing to only adopting the single model. In this paper, a flexible and robust MVI algorithm named EELMimpute is proposed to address missing DNA microarray data imputation problem. First, the algorithm constructs a relevant feature space for the missing target gene, where the relevant feature space only includes those co-expression genes of the target gene based on calculating their Pearson's correlation coefficients. Then, some fix-sized feature subspaces are randomly extracted from the relevant feature space to construct extreme learning machine (ELM) regression models between the extracted genes and the target gene. Furthermore, selecting those models without missing input gene values to construct the ensemble framework, and then imputing the missing gene by calculating the average output of all models included in the ensemble framework. Experimental results show that the EELMimpute algorithm is able to reduce the estimated errors in comparison with several previous imputation algorithms.
HA/GO hybrid hydrogels with adjustable mechanical property were prepared via an in-situ free-radical polymerization, and then utilized for ex vivo expansion of CD34+ cells. Subsequently, the ...influence of physical property of the hydrogels on ex vivo expansion of CD34+ cells was evaluated.
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•A novel HA/GO hybrid hydrogels was first prepared by in-situ free-radical polymerization.•The hydrogels have adjustable mechanical property.•The hydrogels could support the expansion of CD34+ cells ex vivo.
HA/GO hydrogels were prepared by methacrylated GO (MeGO) and methacrylated HA (MeHA) via an in-situ free radical polymerization, and then a series of HA/GO hydrogels with highly porous structure were obtained. All hydrogels exhibited excellent water absorption ability. Additionally, the elastic moduli of hydrogels were clearly enhanced by GO. CD34+ cells cultured on HA/GO-0.05 hydrogel showed higher expansion of CD34+ cells and CD34+CD38− cells compared to the other three hydrogels. Therefore, HA/GO-0.05 hydrogels have a potential for clinical-applied ex vivo expansion of hematopoietic stem cells.
Polyhedral oligomeric silsesquioxanes (POSS)-based hybrid hydrogels were successfully prepared
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a fast azide-alkyne click reaction between octa-azido-functionalized POSS (OAPOSS) and ...alkyne-functionalized poly(ethylene glycol) (PEG). A series of hybrid POSS-PEG hydrogels with the highly ordered porous structures were achieved and the pore size could be well controlled by varying the PEG chain length to 3k, 6k and 10k. After immersing in phosphate buffered saline (PBS), POSS-PEG hydrogels exhibited a good water absorption capacity, and their swelling ratio increased with the increase of the PEG chain length. Rheological measurements indicated that all hydrogels exhibited the characteristics of an elastomer. The elastic modulus and ultimate stress (at break) were significantly enhanced with the increase of the PEG chain length which has been revealed by stress–strain mechanical analysis.
In vitro
cell culture showed that all POSS-PEG hydrogels could well support chondrocytes attachment, spreading and proliferation, especially for the POSS-PEG (10k) hydrogel. Thus, POSS-PEG hydrogels exhibited the potential for cartilage tissue engineering.
Reactive oxygen species (ROS) level is closely associated with the physiological function of hematopoietic stem cells (HSCs) in ex vivo culture systems. Previously developed hydrogels in use of HSCs ...culture have generally failed in considering their antioxidant property. In the present work, antioxidant hydrogels are constructed to evaluate the biological effect of ROS on HSCs proliferation by suppressing oxidative stress damage. Functionalized carbon nanotubes (CNTs), which act as potential antioxidants, are physically encapsulated in biocompatible hyaluronic acid (HA) hydrogels to achieve long‐term antioxidant activity. Consequently, these hybrid hydrogels exhibit enhanced physical properties and superior scavenging capability on oxides and peroxides compared to the pure HA hydrogel. The results indicate that ROS significantly inhibit the biological characteristics of HSCs. Nevertheless, the proliferation ability and pluripotency are dramatically improved when the culture system is supplied with the antioxidant hydrogel, revealing that the CNT‐incorporated hydrogel can effectively relieve oxidative stress response in HSCs and reduce apoptosis from ROS. Therefore, the HA/CNT hydrogel can provide a novel strategy to establish an artificial microenvironment with a low ROS level for HSCs proliferation.
A series of hybrid hydrogels based on hyaluronic acid and oxidized carbon nanotubes are developed, which show the enhanced physical properties and long‐term antioxidant activity. Hematopoietic stem cells incubated with antioxidant hydrogels exhibit evidently higher proliferation rate and more primary phenotypes, as well as better pluripotency.
The development of artificial bone substitutes mimicking the extracellular matrix is a promising strategy for bone repair and regeneration. However, the preparation of materials tailored to feature ...sufficient mechanical properties, appropriate degradation rates, and favorable osteoinductivity continues to be a great challenge. Hydrogels from biopolymers have emerged as viable substitutes in bone regeneration, but they often suffer from insufficient mechanical strength and rapid degradation rate, critically limiting their clinical applicability. Here, we demonstrate that inorganic/biopolymer hybrid hydrogels formed through photo-cross-linking of methacrylated gelatin (Gel) and octamethacrylated polyhedral oligomeric silsesquioxane (OMAPOSS) nanocages can be tailored to possess high mechanical strength, more appropriate degradation rate, and provide biological activity to meet tissue growth demands outperforming simple Gel hydrogels without POSS. Moreover, Gel-POSS hybrid hydrogels effectively promote mesenchymal stem cell (MSC) attachment, spreading, and proliferation, and, critically enhance the osteogenesis of MSCs as evidenced by improved bone repair in a rat calvarial defect model. Hence, such POSS-enhanced synthetically tailored hybrid hydrogels represent a promising concept for long-term bone tissue regeneration.
Ex vivo expansion of hematopoietic stem cells (HSCs) with most current methods can hardly satisfy clinical application requirement. While in vivo, HSCs efficiently self‐renew in niche where they ...interact with 3D extracellular matrix and stromal cells. Therefore, co‐cultures of CD34+ cells and mesenchyme stem cells derived from human amniotic membrane (hAMSCs) on the basis of biomimetic macroporous three‐dimensional (3D) poly(ε‐caprolactone) (PCL) scaffolds are developed, where scaffolds and hAMSCs are applied to mimic structural and cellular microenvironment of HSCs. The influence of scaffolds, feeder cells, and contact manners on expansion and stemness maintenance of CD34+ cells is investigated in this protocol. Biomimetic scaffolds‐dependent co‐cultures of CD34+ cells and hAMSCs can effectively promote the expansion of CD34+ cells; meanwhile, indirect contact is superior to direct contact. The combination of biomimetic scaffolds and hAMSCs represents a new strategy for achieving clinical‐scale ex vivo expansion of CD34+ cells.
Biomimetic macroporous poly(ε‐caprolactone) (PCL) scaffolds and feeder cells (human amniotic membrane‐derived stromal cells) are utilized in hematopoietic cultures to mimic the physical and biological parameters of hematopoietic stem cell niche. Four culture conditions are designed to evaluate the influence of PCL scaffolds, feeder cells, and contact manner on ex vivo expansion of HSPCs.
Objectives
Stem cell factor (SCF) is considered as a commonly indispensable cytokine for proliferation of haematopoietic stem cells (HSCs), which is used in large dosages during ex vivo culture. The ...work presented here aimed to reduce the consumption of SCF by sustained release but still support cells proliferation and maintain the multipotency of HSCs.
Materials and methods
Stem cell factor was physically encapsulated within a hyaluronic acid/gelatin double network (HGDN) hydrogel to achieve a slow release rate. CD34+ cells were cultured within the SCF‐loaded HGDN hydrogel for 14 days. The cell number, phenotype and functional capacity were investigated after culture.
Results
The HGDN hydrogels had desirable properties and encapsulated SCF kept being released for more than 6 days. SCF remained the native bioactivity, and the proliferation of HSCs within the SCF‐loaded HGDN hydrogel was not affected, although the consumption of SCF was only a quarter in comparison with the conventional culture. Moreover, CD34+ cells harvested from the SCF‐loaded HGDN hydrogels generated more multipotent colony‐forming units (CFU‐GEMM).
Conclusion
The data suggested that the SCF‐loaded HGDN hydrogel could support ex vivo culture of HSCs, thus providing a cost‐effective culture protocol for HSCs.
Combination therapy has gained enormous attention due to its high effectiveness in killing cancer cells. Herein, a novel reduction-responsive drug carrier based on amphiphilic dendritic copolymer was ...constructed for the combination treatment of chemotherapy with photodynamic therapy (PDT). The porphyrin (TPP) disulfide coupled third-generation dendronized poly(ethylene glycol) (PEG-G3-OH) copolymer (TPP-S-S-G3) was synthesized
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disulfide linkages between dendritic polyester and porphyrin photosensitizers, which could further self-assemble into spherical micelles in aqueous solution. Compared to the linear TPP-S-S-G0 copolymer, the dendritic TPP-S-S-G3 copolymer could have a higher drug loading content and efficiency. The uptake of doxorubicin (DOX)-loaded TPP-S-S-G3 micelles by MCF-7 cells and intracellular release of porphyrin and DOX was investigated by flow cytometry and CLSM, respectively, and the results exhibited a fast uptake of TPP-S-S-G3 micelles and drug release. Cytotoxicity assay of DOX-loaded TPP-S-S-G3 micelles were evaluated by MTT assay. It indicated that DOX-loaded TPP-S-S-G3 micelles exhibited a higher cellular proliferation inhibition than free DOX, free porphyrin and DOX-loaded linear TPP-S-S-G0 micelles under light irradiation. Thus, the reduction-responsive dendritic copolymer presented the great potential in the combination therapy between chemotherapy and PDT.
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