Intelligent berberine-loaded erythrocytes attenuated inflammatory cytokine productions in macrophages.

Erythrocytes are impressive tools for drug delivery, especially to macrophages. Therefore, berberine was loaded into erythrocytes using both hypotonic pre-swelling and endocytosis methods to target macrophages. Physicochemical and kinetic parameters of the resulting carrier cells, such as drug loading/release kinetics, osmotic fragility, and hematological indices, were determined. Drug loading was optimized for the study using Taguchi experimental design and lab experiments. Loaded erythrocytes were targeted to macrophages using ZnCl2 and bis-sulfosuccinimidyl-suberate, and targeting was evaluated using flow cytometry and Wright-Giemsa staining. Differentiated macrophages were stimulated with lipopolysaccharide, and the inflammatory profiles of macrophages were evaluated using ELISA, western blotting, and real-time PCR. Findings indicated that the endocytosis method is preferred due to its low impact on the erythrocyte's structural integrity. Maximum loading achieved (1386.68 ± 22.43 µg/ml) at 1500 µg/ml berberine treatment at 37 °C for 2 h. Berberine successfully inhibited NF-κB translation in macrophages, and inflammatory response markers such as IL-1ß, IL-8, IL-23, and TNF-α were decreased by approximately ninefold, sixfold, twofold, eightfold, and twofold, respectively, compared to the LPS-treated macrophages. It was concluded that berberine-loaded erythrocytes can effectively target macrophages and modulate the inflammatory response.

Bacterial Ocular Infections in Iran: A Systematic Review and Meta-analysis.

Objectives: Eye infections can be caused by several microorganisms and the most common causative bacterial agents are staphylococci, streptococci, and Pseudomonas aeruginosa. This study aimed to estimate the prevalence of Staphylococcus aureus, Staphylococcus epidermidis, viridans group streptococci, and P. aeruginosa as the cause of ocular infections in Iran. Methods: We conducted a systematic search on the studies published by Iranian authors from January 2000 to December 2020 in Web of Science, PubMed, Scopus, and Embase. Eligible studies were selected according to the defined inclusion/exclusion criteria. Statistical heterogeneity between and within groups was estimated by the Q-statistic and I2 index. The funnel plots, Duval and Tweedie trim, and fill methods were obtained to evaluate the evidence of publication bias. Results: Twenty-seven studies were included in this review. According to the meta-analysis results, the prevalence of S.epidermidis was 19.1% (95% CI: 12.5-28.1). It was estimated 6.9% (95% CI: 4.4-10.6), 6.7% (95% CI: 4.6-9.6), and 3.3% (95% CI: 1.8-5.8) for P.aeruginosa, S. aureus, and viridans streptococci, respectively. Conclusions: S. epidermidis is the prevalent bacterial agents responsible for eye-associated infections in Iran.

Cationic, anionic and neutral polysaccharides for skin tissue engineering and wound healing applications.

Today, chronic wound care and management can be regarded as a clinically critical issue. However, the limitations of current approaches for wound healing have encouraged researchers and physicians to develop more efficient alternative approaches. Advances in tissue engineering and regenerative medicine have resulted in the development of promising approaches that can accelerate wound healing and improve the skin regeneration rate and quality. The design and fabrication of scaffolds that can address the multifactorial nature of chronic wound occurrence and provide support for the healing process can be considered an important area requiring improvement. In this regard, polysaccharide-based scaffolds have distinctive properties such as biocompatibility, biodegradability, high water retention capacity and nontoxicity, making them ideal for wound healing applications. Their tunable structure and networked morphology could facilitate a number of functions, such as controlling their diffusion, maintaining wound moisture, absorbing a large amount of exudates and facilitating gas exchange. In this review, the wound healing process and the influential factors, structure and properties of carbohydrate polymers, physical and chemical crosslinking of polysaccharides, scaffold fabrication techniques, and the use of polysaccharide-based scaffolds in skin tissue engineering and wound healing applications are discussed.

Effects of Xenogen Mesenchymal Stem Cells and Cryo-Platelet Gel on Intractable Wound Healing in Animal Model (Rat).

BACKGROUND: Today, the effects of growth factors and mesenchymal stem cells (MSCs) in promoting wound healing has been confirmed. OBJECTIVE: This study aimed to investigate the effect of MSCs and platelet cryogel on wound healing. METHODS: 40 male wistar rats were randomly divided into five groups (n=8). The control group was just dressed, the second group received platelet cryogel, the third group received platelet cryogel containing MSCs, the fourth group received plasma, and the fifth group received plasma plus MSCs. The biopsy was obtained from the wounds in the 2, 4, 6, and 8 days of the treatment. Then, pathological evaluation was conducted. Finally, qRT-PCR was performed to determine angiogenesis. RESULTS: The intervention groups had faster wound healing and lower wound area than the control group (p<0.05). The highest wound healing rate and the smallest wound area was observed in the group receiving platelet cryogel plus MSCs. Angiogenesis, fibrosis, myoepithelial and epithelialization in the pathologic examination using H & E staining were not significantly different between the groups. The expression of Ang-1 in the intervention groups was higher than the control group and the highest expression was observed in the platelet cryogel plus MSCs, followed by the platelet cryogel group. The expression of VEGF in the plasma plus MSCs was higher than in the other groups. CONCLUSION: Further studies require to determine the effects of combined use of platelet cryogel plus MSCs on other types of wound and evaluate mechanisms involved in wound healing like collagenesis and inflammatory factors.

Nanocomposite scaffolds for accelerating chronic wound healing by enhancing angiogenesis.

Skin is the body's first barrier against external pathogens that maintains the homeostasis of the body. Any serious damage to the skin could have an impact on human health and quality of life. Tissue engineering aims to improve the quality of damaged tissue regeneration. One of the most effective treatments for skin tissue regeneration is to improve angiogenesis during the healing period. Over the last decade, there has been an impressive growth of new potential applications for nanobiomaterials in tissue engineering. Various approaches have been developed to improve the rate and quality of the healing process using angiogenic nanomaterials. In this review, we focused on molecular mechanisms and key factors in angiogenesis, the role of nanobiomaterials in angiogenesis, and scaffold-based tissue engineering approaches for accelerated wound healing based on improved angiogenesis.

Stem cell-based therapeutic strategies for corneal epithelium regeneration.

Any significant loss of vision or blindness caused by corneal damages is referred to as corneal blindness. Corneal blindness is the fourth most common cause of blindness worldwide, representing more than 5% of the total blind population. Currently, corneal transplantation is used to treat many corneal diseases. In some cases, implantation of artificial cornea (keratoprosthesis) is suggested after a patient has had a donor corneal transplant failure. The shortage of donors and the side effects of keratoprosthesis are limiting these approaches. Recently, researchers have been actively pursuing new approaches for corneal regeneration because of these limitations. Nowadays, tissue engineering of different corneal layers (epithelium, stroma, endothelium, or full thickness tissue) is a promising approach that has attracted a great deal of interest from researchers and focuses on regenerative strategies using different cell sources and biomaterials. Various sources of corneal and non-corneal stem cells have shown significant advantages for corneal epithelium regeneration applications. Pluripotent stem cells (embryonic stem cells and iPS cells), epithelial stem cells (derived from oral mucus, amniotic membrane, epidermis and hair follicle), mesenchymal stem cells (bone marrow, adipose-derived, amniotic membrane, placenta, umbilical cord), and neural crest origin stem cells (dental pulp stem cells) are the most promising sources in this regard. These cells could also be used in combination with natural or synthetic scaffolds to improve the efficacy of the therapeutic approach. As the ocular surface is exposed to external damage, the number of studies on regeneration of the corneal epithelium is rising. In this paper, we reviewed the stem cell-based strategies for corneal epithelium regeneration.

Preparation and characterization of poly(ethylene oxide)/zinc oxide nanofibrous scaffold for chronic wound healing applications.

BACKGROUND: Skin, the first barrier to pathogens, loses its integrity and function after an injury. The presence of an antibacterial dressing at the wound site may prevent bacterial invasion and also improve the healing process. OBJECTIVES: The current study aimed to fabricate a biomimetic membrane with antibacterial properties for healing chronic wounds. MATERIAL AND METHODS: The membranes, fabricated through electrospinning, are comprised of poly(ethylene oxide) (PEO) and zinc oxide nanoparticles (ZnO-NPs) as the main biomaterial and antibacterial agent, respectively. Antibacterial activity, cell attachment and viability were tested to evaluate the biological properties of the membranes. The optimal cell compatible concentration of ZnO-NPs was determined for further studies. In vitro characterization of the membranes was performed to confirm their suitable properties for wound healing. RESULTS: The antibacterial PEO/ZnO-NP membrane containing 2% of nanoparticles showed no cell toxicity, and human fibroblast cells were able to adhere and proliferate on the scaffold. The in vitro results from the tensile test, wettability, porosity, and protein adsorption revealed appropriate properties of the membrane as a scaffold for skin tissue engineering. CONCLUSIONS: Synthetic polymers have been widely used for tissue engineering applications. The proper characteristics of PEO nanofibers, including a high ratio of surface/volume, moderate hydrophilicity and good mechanical properties, make this polymer interesting for skin regeneration. The results demonstrate the potential of the antibacterial PEO/ZnO-NP membrane to be used as an engineered scaffold to improve the wound healing process.

Biopolymer-based scaffolds for corneal stromal regeneration: A review.

The stroma is one of the 5 layers of the cornea that comprises more than 90% of the corneal thickness, and is the most important layer for the transparency of cornea and refractive function critical for vision. Any significant damage to this layer may lead to corneal blindness. Corneal blindness refers to loss of vision or blindness caused by corneal diseases or damage, which is the 4th most common cause of blindness worldwide. Different approaches are used to treat these patients. Severe corneal damage is traditionally treated by transplantation of a donor cornea or implantation of an artificial cornea. Other alternative approaches, such as cell/stem cell therapy, drug/gene delivery and tissue engineering, are currently promising in the regeneration of damaged cornea. The aim of tissue engineering is to functionally repair and regenerate damaged cornea using scaffolds with or without cells and growth factors. Among the different types of scaffolds, polymer-based scaffolds have shown great potential for corneal stromal regeneration. In this paper, the most recent findings of corneal stromal tissue engineering are reviewed.

Isolation, identification and differentiation of human spermatogonial cells on three-dimensional decellularized sheep testis.

Improvement of in vitro culture methods of Spermatogonial Stem Cells (SSCs) is known to be an effective procedure for further study of the process of spermatogenesis and can offer effective therapeutic modality for male infertility. Tissue decellularization by providing natural 3D and extracellular matrix (ECM) conditions for cell growth can be an alternative procedure to enhance in vitro culture conditions. In the present study, the testicular tissues were taken from brain death donors. After enzymatic digestion, the tissue cells were isolated and cultured for four weeks. Then the identity of the SSCs was confirmed using anti-GFRα1 and anti-PLZF antibodies via immunocytochemistry (ICC). The differentiation capacity of SSCs were evaluated by culture of them on a layer of decellularized testicular matrix (DTM) prepared from sheep testis, as well as under two-dimensional (2D) culture with differentiation medium. After four and six weeks of the initiation of differentiation culture, the pre-meiotic, meiotic and post- meiotic genes at the mRNA and protein levels was examined via qPCR and ICC methods, respectively. The results showed that pre-meiotic, meiotic and post-meiotic genes expressions were significantly higher in the cells cultured in DTM substrate (P ≤ 0.01).The present study indicated that, the natural structure of ECM prepare the suitable conditions for further study of the spermatogenesis process in the in vitro and contributes to the maintenance and treatment of male infertility.

Does survivin overexpression enhance the efficiency of fibroblast cell-based wound therapy?

Cell-based wound therapy is faced with some limiting factors that decrease the therapeutic efficacy of transplanted cells. In this study, we aimed to genetically modify fibroblast cells with anti-apoptotic Survivin gene (Birc5) before cell transplantation. In vitro, pIRES2-eGFP-Survivin plasmid was transfected into the fibroblast cells and the growth curve was evaluated for transfected and normal cells performing MTT assay. In vivo, two 6-diameter cutaneous wounds were created at mice dorsal skin. Fibrin clot was used as a delivery vehicle to transfer cells into the wound bed. The effects of four treatment groups including (a) Cell-SVV-Clot (b) Cell-GFP-Clot, (c) Normal cell-Clot and, (d) Clot alone were evaluated. After 1,2,3,7 and 14 days post-transplantation, the wounds were photographed for evaluating the wound closure rate and wound samples were obtained. Angiogenesis and formation of granulated tissue were assessed via H&E staining for wound samples. The expression levels of Survivin, VEGF, and bFGF genes were also determined using qRT-PCR. The MTT assay showed similar proliferation potential of transfected cells with normal cells verifying that Survivin had no detrimental effect. Compared to the Normal cell-Clot group, the Survivin overexpression was seen for 3 days in the Cell-SVV-Clot group verifying the cell survival during the early stage of wound healing. The Survivin further upregulated VEGF and bFGF expressions resulting in more angiogenesis and formation of granulated tissue by day 3 and 14. The treated wounds with Cell-SVV-Clot were regenerated with a higher wound closure rate by day 7 compared to Normal cell-Clot and Clot groups. Survivin enhanced wound healing through induction of VEGF and bFGF at particular times post-wounding that led to a more structured-epidermis with higher angiogenesis and granulation tissue formation rate.

Monophosphoryl Lipid A and Retinoic Acid Combinations Increased Germ Cell Differentiation Markers Expression in Human Umbilical Cord-derived Mesenchymal Stromal Cells in an In vitro Ovine Acellular Testis Scaffold.

Infertility is known as one of the most common problems among couples. In this regard, generation of male germ cells from adult stem ones are among the current promising priorities of researchers. Mesenchymal stromal cells (MSCs) were previously induced to differentiate into germ-like progenitors in vitro. Monophosphoryl lipid A (MPLA) is a detoxified derivative of lipopolysaccharides (LPS) that lacks many of the endotoxic properties of LPS. Our present study aimed to investigate the expression of migration genes (CXCR4, VCAM1, VEGF, MMP2, and VLA4), and differentiation markers during human umbilical mesenchymal stromal cells (hUMSCs) culture in the presence of retinoic acid (RA) and MPLA-treated acellular testis. Accordingly, the high expression levels of deleted in azoospermia-like (DAZL), piwi-like RNA-mediated gene silencing 2 (PIWIL2) transcripts as well as protein were consequently observed in treated hUMSCs. It was concluded that combination treatment (i.e., MPLA/RA) had more prominent results than each of the treatments alone, even though MPLA and RA could be regarded as inducer of migration and differentiation, respectively. Ultimately, it was suggested to introduce the use of combination treatment as a more effective strategy to improve therapies in regenerative medicine.

A potential hypothesis for 2019-nCoV infection therapy through delivery of recombinant ACE2 by red blood cell-hitchhiking.

A novel infectious disease, caused by 2019 Novel Coronavirus (2019-nCoV) is responsible for the recent outbreak of severe respiratory disease. The 2019-nCoV spread rapidly and reaching epidemic proportions in many countries of the world. ACE2 was identified as a key receptor for 2019-nCoV infections. Excessive form of soluble ACE2 rescues cellular ACE2 activity which has a protective role in acute lung failure and neutralizes the virus. The short half-life of ACE2 is a major limitation to its practical application. Nanoparticle-based drug delivery systems are one of the most widely investigated approaches for developing novel therapies for a variety of diseases. Nevertheless, nanoparticles suffer from the rapid removal from the bloodstream by the reticuloendothelial system (RES). A noncovalent attachment of nanoparticles to RBCs increases their half-life in blood and allows transient accumulation in the lungs, while decreases their uptake by the liver and spleen. Connecting the recombinant ACE2 into the surface of nanoparticles that were attached to RBCs can be a potential therapeutic approach for 2019-nCoV infection through increasing their lung targeting to naturalize the virus and also acting as a bioreactor in the blood circulation to decrease serum level of Angiotensin II and protects lungs from injury/ARDS.

Increased in vitro migration of human umbilical cord mesenchymal stem cells toward acellular foreskin treated with bacterial derivatives of monophosphoryl lipid A or supernatant of Lactobacillus acidophilus.

Migration and homing are known as critical steps toward regeneration of damaged tissues via cell therapies. Among various cellular sources of stem cells, the umbilical cord has been thus recognized as an interesting one endowed with high benefits. Accordingly, the main objective of the present study was to determine whether monophosphoryl lipid A (MPLA) or supernatant of Lactobacillus acidophilus (SLA) could increase migration of human umbilical cord mesenchymal stem cells (hUMSCs) toward acellular foreskin or not. In this study, the hUMSCs were isolated and cultured through acellular MPLA- or SLA-treated foreskin. Expression of some migration genes (i.e., VCAM-1, MMP-2, VLA-4, CXCR-4, and VEGF) was also investigated using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). Moreover; vimentin, cytokeratin 5 (CK5), and matrix metalloproteinases-2 (MMP-2) were detected via immunohistochemistry (IHC) analysis. The hUMSCs in the presence of MPLA- or SLA-treated foreskin showed more tissue tropism compared with those in the control group. Besides, the scanning electron microscopy (SEM) results established that the hUMSCs had more migratory activity in the presence of MPLA- or SLA-treated foreskin than the untreated one. The IHC analysis results correspondingly indicated that expression of vimentin, CK5, and MMP-2 proteins had augmented in both treatments compared with those in the control group. It was concluded that MPLA had revealed more prominent results than SLA, even though both treatments could be regarded as inducing factors in migration. Ultimately, it was suggested to introduce the use of MPLA and probiotic components as a promising approach to improve therapies in regenerative medicine.

Beta-Secretase 1 (BACE1) Is Down-Regulated in Invasive Ductal Carcinoma of Breast.

BACKGROUND: The enzyme beta-secretase 1 (BACE1) and its antisense transcript (BACE1-AS) have been implicated in the pathogenesis of Alzheimer's disease. Moreover, several lines of evidence point to their contribution in tumorigenesis. METHODS: In the present study, we evaluated expression of BACE1 mRNA (BACE1) and BACE1-AS in 54 breast cancer tissues and 54 adjacent non-cancerous tissues (ANCTs) from the same patients using quantitative real-time PCR. RESULTS: BACE1 was significantly down-regulated in tumoral tissues compared with ANCTs, while BACE1- AS expression was not significantly different between tumoral tissues and ANCTs. The Bayesian Multilevel model showed a significant difference in BACE1 expression between stage 1 and 2 cancers after age-effect adjustments. BACE1-AS expression was significantly greater in ER-positive than in ER-negative samples (P=0.01). BACE1 and BACE1-AS expression were not correlated with patient ages in any sample sets. CONCLUSION: Significant correlations were detected between expression of these genes in both tumoral tissues and ANCTs. The current study provides evidence for differential BACE1 expression in breast tissues and suggests further assessment of the role of BACE1 in the pathogenesis of cancer.

A review on different methods to increase the efficiency of mesenchymal stem cell-based wound therapy.

Mesenchymal stem cells (MSCs) accelerate wound healing but the harsh environment of wound site limits the engraftment, retention, and survival rate of transplanted cells. There are multiple approaches that amplify the therapeutic potential of MSCs. The MSCs derived from medical waste material, provide comparable regenerative abilities compared to traditional sources. The application of different scaffolds increases MSC delivery and migration into the wound. The spheroid culture of MSC increases the paracrine effects of the entrapped cells and the secretion of pro-angiogenic and anti-inflammatory cytokines. The MSC pretreating and preconditioning enhances the cell migration, proliferation, and survival rate, which lead to higher angiogenesis, re-epithelialization, wound closure, and granulation tissue formation. Moreover, genetic modification has been performed in order to increase MSC angiogenesis, differentiation potential, as well as the cell life span. Herein, we review the results of aforementioned approaches and provide information accommodating to the continued development of MSC-based wound therapy in the future.

Trace of survivin in cancer.

Survivin is one of the most cancer-specific proteins overexpressed in almost all malignancies, but is nearly undetectable in most normal tissues in adults. Functionally, as a member of the inhibitor of apoptosis family, survivin has been shown to inhibit apoptosis and increase proliferation. The antiapoptotic function of survivin seems to be related to its ability to inhibit caspases directly or indirectly. Furthermore, the role of survivin in cell cycle division control is related to its role in the chromosomal passenger complex. Consistent with its determining role in these processes, survivin plays a crucial role in cancer progression and cancer cell resistance to anticancer drugs and ionizing radiation. On the basis of these findings, recently survivin has been investigated intensively as an ideal tumor biomarker. Thus, multiple molecular approaches such as use of the RNA interfering technique, antisense oligonucleotides, ribozyme, and small molecule inhibitors have been used to downregulate survivin regulation and inhibit its biological function consequently. In this review, all these approaches are explained and other compounds that induced apoptosis in different cell lines through survivin inhibition are also reported.

In Vitro Spermatogenesis by Three-dimensional Culture of Spermatogonial Stem Cells on Decellularized Testicular Matrix.

BACKGROUND: In the males, Spermatogonial Stem Cells (SSCs) contribute to the production of sex cells and fertility. In vitro SSCs culture can operate as an effective strategy for studies on spermatogenesis and male infertility treatment. Cell culture in a three-dimensional (3D) substrate, relative to a two-dimensional substrate (2D), creates better conditions for cell interaction and is closer to in vivo conditions. In the present study, in order to create a 3D matrix substrate, decellularized testicular matrix (DTM) was used to engender optimal conditions for SSCs culture and differentiation. MATERIALS AND METHODS: After, testicular cells enzymatic extraction from testes of brain-dead donors, the SSCs were proliferated in a specific culture medium for four weeks, and after confirming the identity of the colonies derived from the growth of these cells, they were cultured on a layer of DTM as well as in 2D condition with a differentiated culture medium. In the Sixth week since the initiation of the differentiation culture, the expression of pre meiotic (OCT4 & PLZF ), meiotic (SCP3 & BOULE) and post meiotic (CREM & Protamine-2) genes were measured in both groups. RESULTS: The results indicated that the expression of pre meiotic, meiotic and post meiotic genes was significantly higher in the cells cultured on DTM (P ≤ 0.001). CONCLUSION: SSCs culture in DTM with the creation of ECM and similar conditions with in vivo can be regarded as a way of demonstrating spermatogenesis in vitro, which can be adopted as a treatment modality for male infertility.

Migration Gene Expression of Human Umbilical Cord Mesenchymal Stem Cells: A Comparison between Monophosphoryl Lipid A and Supernatant of Lactobacillus acidophilus.

The capacity of human umbilical cord mesenchymal stem cells (hUMSCs) for migration and homing is very important in regenerative medicine. A detoxified derivative of lipopolysaccharides (LPS) that lacks many of the endotoxic properties of LPS is monophosphoryl lipid A (MPLA). Effects of MPLA on the induction of MSCs migration, have not yet been studied. Also, studies have shown that supernatant of Lactobacillus acidophilus (SLA) culture medium, can stimulate the proliferation of macrophages and lymphocytes in vitro by affecting the properties of the chemotaxis and angiogenesis. Our present study aimed to understanding of the migration of hUMSCs during treatment with MPLA and SLA, separately. HUMSCs were isolated from human umbilical cord and were characterized by investigating surface markers (CD105, CD90, anti-CD29, CD45, and CD34) and their differentiation into adipogenic and osteogenic lineages. HUMSCs were treated with MPLA (10-3 µg/ml) and SLA (3 µl/ml). The morphological changes were not observed in both treated MSCs. Expression levels of migration markers were determined by quantitative reverse transcription PCR analysis on 2, 4, 6 days after treatment. Results showed that VEGF and MMP-2 but not CXCR-4 was increased in the presence of both treatments. Also, SLA led to a decrease and increase of the expression of VLA-4 and VCAM-1, respectively, while MPLA increased both VLA-4 and VCAM-1 expression.Therefore, it can be suggested that MPLA has more prominent results than SLA, but both treatments can probably be considered as an inducing factor in migration.

A Simple, Rapid, and Efficient Method for Isolating Mesenchymal Stem Cells From the Entire Umbilical Cord.

Several reports have been published on the isolation, culture, and identification of mesenchymal stem cells (MSCs) from different anatomical regions of the umbilical cord (UC). UC is suitable for standardizing methods of MSC isolation because it is a uniform source with high MSC numbers. Although the UC is considered a medical waste after childbirth, ethical issues for its use must be considered. An increased demand for MSCs in regenerative medicine has made scientists prioritize the development of MSC isolation methods. Several research groups are attempting to provide a large number of high-quality MSCs. In this study, we present a modulated explant/enzyme method (MEEM) to isolate the maximum number of MSCs from the entire UC. This method was established for the isolation of MSCs from different anatomical regions of the UC altogether. We could retrieve 6 to 10 million MSCs during 8 to 10 days of primary culture. After three passages, we could obtain 8-10 × 10(8) cells in 28-30 days. MSCs isolated by this method express CD73, CD90, CD105, and CD44, but they do not express hematopoietic markers CD34 and CD45 or the endothelial marker CD31. The genes SOX2, OCT4, and NANOG are expressed in isolated MSCs. The capacity of these MSCs to differentiate into adipocytes and osteocytes highlights their application in regenerative medicine. This method is simple, reproducible, and cost efficient. Moreover, this method is suitable for the production of a large number of high-quality MSCs from an UC in less than a month, to be used for cell therapy in an 80-kg person.

Compressive-sampling-based positioning in wireless body area networks.

Recent achievements in wireless technologies have opened up enormous opportunities for the implementation of ubiquitous health care systems in providing rich contextual information and warning mechanisms against abnormal conditions. This helps with the automatic and remote monitoring/tracking of patients in hospitals and facilitates and with the supervision of fragile, elderly people in their own domestic environment through automatic systems to handle the remote drug delivery. This paper presents a new modeling and analysis framework for the multipatient positioning in a wireless body area network (WBAN) which exploits the spatial sparsity of patients and a sparse fast Fourier transform (FFT)-based feature extraction mechanism for monitoring of patients and for reporting the movement tracking to a central database server containing patient vital information. The main goal of this paper is to achieve a high degree of accuracy and resolution in the patient localization with less computational complexity in the implementation using the compressive sensing theory. We represent the patients' positions as a sparse vector obtained by the discrete segmentation of the patient movement space in a circular grid. To estimate this vector, a compressive-sampling-based two-level FFT (CS-2FFT) feature vector is synthesized for each received signal from the biosensors embedded on the patient's body at each grid point. This feature extraction process benefits in the combination of both short-time and long-time properties of the received signals. The robustness of the proposed CS-2FFT-based algorithm in terms of the average positioning error is numerically evaluated using the realistic parameters in the IEEE 802.15.6-WBAN standard in the presence of additive white Gaussian noise. Due to the circular grid pattern and the CS-2FFT feature extraction method, the proposed scheme represents a significant reduction in the computational complexity, while improving the level of the resolution and the localization accuracy when compared to some classical CS-based positioning algorithms.