Types Of Adult Stem Cells Research Articles

Stem cells in dentistry: A study regarding awareness of stem cells among dental professionals.

Dental stem cell, a type of adult stem cell, exhibits multipotent differentiation capacity and is drawing worldwide attention because of its numerous applications. The advances in applications of dental stem cells seem to be unsurpassed in the near future, for which specialized skills and knowledge in this arena are of prime significance. Hence, there is a need to acquire more knowledge about dental stem cells to obtain maximum benefits from it in the coming years. Dental stem cells in India are still at the budding stage, and there seems to be limited awareness regarding dental stem cells. This study aimed to assess the awareness of stem cells among the dental professionals. The present study was a questionnaire-based study of dental professionals (MDS, BDS, postgraduates, and interns) of three different institutions. Results showed that 95.2% of dental professionals are aware of the terminology dental stem cells and 53.9% of them are aware of various applications of dental stem cells. Chi-square test showed a significant correlation between the sources of information, source of dental stem cells, and clinical applications in relation to the academic qualification of the dental professionals. This study revealed a good level of awareness among the dental professionals, and it also showed the need to spread more knowledge about the advances in applications, storage, banking, and guidelines related to dental stem cells.

Effect of pregnancy on the proliferation of rat adipose-derived stem cells.

Stem cell therapy faces many problems including poor survival rates and low viability. Enhancing the biological functions of stem cells improves efficacy of therapies. Estrogen, whose levels are elevated during pregnancy, affects the properties of bone marrow mesenchymal stem cells. Evidence suggests that adipose-derived stem cells (ADSCs), which are a type of adult mesenchymal stem cells, can be used in regenerative medicine. In fact, ADSCs from pregnant animals have been used in clinical therapies. However, the effect of the donor's reproductive status on proliferation of ADSCs is unknown. We investigated the effect of 17β-estradiol (E2) and progesterone (P) on the in vitro proliferation of ADSCs from laboratory rats. ADSCs were obtained from five different groups of 15 rats each - non-pregnant, pregnant, in perinatal period, non-pregnant and treated with E2, and non-pregnant and treated with P. Adhesion and viability of ADSCs were determined by MTT assay, and cell cycle was followed by flow cytometry. The proliferation rate of ADSCs from pregnant rats was significantly higher than those from the non-pregnant rats (P < 0.05); however, there was no statistically significant difference in proliferation rates during different phases of pregnancy (P > 0.05). Additionally, ADSCs from pregnant rats possess higher adhesion property in early stage (P1 passage) and higher proliferation rate than ADSCs from non-pregnant rats. Interestingly, ADSCs from non-pregnant rats that were treated with E2, but not those treated with P, showed higher proliferation rates than those from their untreated counterparts. These results suggest that the proliferative capacity and residence time in different cell cycle phases of ADSCs can be regulated by extrinsic factors such as estrogen concentration.

Human endometrial regenerative cells alleviate carbon tetrachloride-induced acute liver injury in mice.

BackgroundThe endometrial regenerative cell (ERC) is a novel type of adult mesenchymal stem cell isolated from menstrual blood. Previous studies demonstrated that ERCs possess unique immunoregulatory properties in vitro and in vivo, as well as the ability to differentiate into functional hepatocyte-like cells. For these reasons, the present study was undertaken to explore the effects of ERCs on carbon tetrachloride (CCl4)–induced acute liver injury (ALI).MethodsAn ALI model in C57BL/6 mice was induced by administration of intraperitoneal injection of CCl4. Transplanted ERCs were intravenously injected (1 million/mouse) into mice 30 min after ALI induction. Liver function, pathological and immunohistological changes, cell tracking, immune cell populations and cytokine profiles were assessed 24 h after the CCl4 induction.ResultsERC treatment effectively decreased the CCl4-induced elevation of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and improved hepatic histopathological abnormalities compared to the untreated ALI group. Immunohistochemical staining showed that over-expression of lymphocyte antigen 6 complex, locus G (Ly6G) was markedly inhibited, whereas expression of proliferating cell nuclear antigen (PCNA) was increased after ERC treatment. Furthermore, the frequency of CD4+ and CD8+ T cell populations in the spleen was significantly down-regulated, while the percentage of splenic CD4+CD25+FOXP3+ regulatory T cells (Tregs) was obviously up-regulated after ERC treatment. Moreover, splenic dendritic cells in ERC-treated mice exhibited dramatically decreased MHC-II expression. Cell tracking studies showed that transplanted PKH26-labeled ERCs engrafted to lung, spleen and injured liver. Compared to untreated controls, mice treated with ERCs had lower levels of IL-1β, IL-6, and TNF-α but higher level of IL-10 in both serum and liver.ConclusionsHuman ERCs protect the liver from acute injury in mice through hepatocyte proliferation promotion, as well as through anti-inflammatory and immunoregulatory effects.

Expression of P2 Purinergic Receptors in Mesenchymal Stem Cells and Their Roles in Extracellular Nucleotide Regulation of Cell Functions.

Extracellular ATP and other nucleotides induce autocrine and/or paracrine purinergic signalling via activation of the P2 receptors on the cell surface, which represents one of the most common signalling mechanisms. Mesenchymal stem cells (MSC) are a type of multipotent adult stem cells that have many promising applications in regenerative medicine. There is increasing evidence to show that extracellular nucleotides regulate MSC functions and P2 receptor-mediated purinergic signalling plays an important role in such functional regulation. P2 receptors comprise ligand-gated ion channel P2X receptors and G-protein-coupled P2Y receptors. In this review, we provide an overview of the current understanding with respect to expression of the P2X and P2Y receptors in MSC and their roles in mediating extracellular nucleotide regulation of MSC proliferation, migration and differentiation. J. Cell. Physiol. 232: 287-297, 2017. © 2016 Wiley Periodicals, Inc.

Lens, heal thyself: a significant advance in regenerative ophthalmology

A few animals, notably Cnidarians, including Hydra and some species of jellyfish, and Planaria possess unlimited regenerative capacity and effectively elude both senescence and biological aging (1). However, humans, and most other vertebrates, exhibit limited regenerative capability for a few tissues that declines with age. Given the isolation of human embryonic stem cells (ESCs), the creation of induced pluripotent stem cells (iPSCs), and the discovery of many adult stem cell types, the drive to harness these cells to reverse the ravages of disease and age captivates the imagination of the public and medical scientists alike. The enthusiasm for unlocking human regenerative potential for clinical use currently drives both private and public research initiatives, giving hope to millions of sight impaired and blind people. For example, the Audacious Goals Initiative, sponsored by The National Eye Institute of the United States, specifically seeks to fund cross-disciplinary research leading to the restoration of vision through retina regeneration.

Tcf7l2 localization of putative stem/progenitor cells in mouse conjunctiva.

Conjunctival integrity and preservation is indispensable for vision. The self-renewing capacity of conjunctival cells controls conjunctival homeostasis and regeneration; however, the source of conjunctival self-renewal and the underlying mechanism is currently unclear. Here, we characterize the biochemical phenotype and proliferative potential of conjunctival epithelial cells in adult mouse by detecting proliferation-related signatures and conducting clonal analysis. Further, we show that transcription factor 7-like 2 (T-cell-specific transcription factor 4), a DNA binding protein expressed in multiple types of adult stem cells, is highly correlated with proliferative signatures in basal conjunctival epithelia. Clonal studies demonstrated that Transcription factor 7-like 2 (Tcf7l2) was coexpressed with p63α and proliferating cell nuclear antigen (PCNA) in propagative colonies. Furthermore, Tcf7l2 was actively transcribed concurrently with conjunctival epithelial proliferation in vitro. Collectively, we suggest that Tcf7l2 may be involved in maintenance of stem/progenitor cells properties of conjunctival epithelial stem/progenitor cells, and with the fornix as the optimal site to isolate highly proliferative conjunctival epithelial cells in adult mice.

Using miRNA-mRNA Interaction Analysis to Link Biologically Relevant miRNAs to Stem Cell Identity Testing for Next-Generation Culturing Development.

Therapeutic benefit of stem cells has been demonstrated in multiple disease models and clinical trials. Robust quality assurance is imperative to make advancements in culturing procedures to enable large-scale cell manufacturing without hampering therapeutic potency. MicroRNAs (miRNAs or miRs) are shown to be master regulators of biological processes and are potentially ideal quality markers. We determined miRNA markers differentially expressed under nonclinical multipotent adult progenitor cell (MAPC) and mesenchymal stem cell (MSC) culturing conditions that regulate important stem cell features, such as proliferation and differentiation. These bone marrow-derived stem cell types were selected because they both exert therapeutic functions, but have different proliferative and regenerative capacities. To determine cell-specific marker miRNAs and assess their effects on stem cell qualities, a miRNA and mRNA profiling was performed on MAPCs and MSCs isolated from three shared donors. We applied an Ingenuity Pathway Analysis-based strategy that combined an integrated RNA profile analysis and a biological function analysis to determine the effects of miRNA-mRNA interactions on phenotype. This resulted in the identification of important miRNA markers linked to cell-cycle regulation and development, the most distinctive being MAPC marker miR-204-5p and MSC marker miR-335-5p, for which we provide in vitro validation of its function in differentiation and cell cycle regulation, respectively. Importantly, marker expression is maintained under xeno-free conditions and during bioreactor isolation and expansion of MAPC cultures. In conclusion, the identified biologically relevant miRNA markers can be used to monitor stem cell stability when implementing variations in culturing procedures. Human adult marrow stromal stem cells have shown great potential in addressing unmet health care needs. Quality assurance is imperative to make advancements in large-scale manufacturing procedures. MicroRNAs are master regulators of biological processes and potentially ideal quality markers. MicroRNA and mRNA profiling data of two human adult stem cell types were correlated to biological functions in silico. Doing this provided evidence that differentially expressed microRNAs are involved in regulating specific stem cell features. Furthermore, expression of a selected microRNA panel was maintained in next-generation culturing platforms, demonstrating the robustness of microRNA profiling in stem cell comparability testing.

A systematic mRNA control mechanism for germline stem cell homeostasis and cell fate specification.

Germline stem cells (GSCs) are the best understood adult stem cell types in the nematode Caenorhabditis elegans, and have provided an important model system for studying stem cells and their cell fate in vivo, in mammals. In this review, we propose a mechanism that controls GSCs and their cell fate through selective activation, repression and mobilization of the specific mRNAs. This mechanism is acutely controlled by known signal transduction pathways (e.g., Notch signaling and Ras-ERK MAPK signaling pathways) and P granule (analogous to mammalian germ granule)-associated mRNA regulators (FBF-1, FBF-2, GLD-1, GLD-2, GLD-3, RNP-8 and IFE-1). Importantly, all regulators are highly conserved in many multi-cellular animals. Therefore, GSCs from a simple animal may provide broad insight into vertebrate stem cells (e.g., hematopoietic stem cells) and their cell fate specification. [BMB Reports 2016; 49(2): 93-98]

Abstract A38: The Wnt noncanonical receptor ROR1 regulates neuroblastoma cell growth and motility through two distinct mechanisms

Abstract Neuroblastoma is a pediatric tumor derived from the sympathetic nervous system, responsible for about 15% of cancer deaths in children. The Wnt signaling pathway, which is required for both normal embryonic development and the maintenance of different types of adult stem cells, including sympathoadrenal progenitors, plays a major role in the onset and progression of several types of human cancer. In a screen of several human neuroblastoma cell lines, we found that none showed a constitutive activation of the canonical Wnt/β-catenin signaling, arguing against a major role of this pathway in this type of cancer. In a previous study, we demonstrated that the receptor tyrosine kinase-like orphan receptor 1 (ROR1) can be triggered by noncanonical Wnt ligands, resulting in its phosphorylation on serine/threonine residues. We found that several neuroblastoma cells express high levels of ROR1, which can be associated in some cases with constitutive phosphorylation of this receptor through an autocrine mechanism. We showed that ROR1 down-regulation through lentiviral shRNAs strongly reduced the growth of different neuroblastoma cells, including SJNB-10, SK-N-AS and Kelly. Conversely, ROR1 knockdown in other neuroblastoma cells significantly reduced cell motility, without affecting growth. To assess the potential role of autocrine noncanonical Wnt signaling in neuroblastoma cell motility and/or growth, we used two different approaches, based on the inhibition of Wnt secretion using the small molecule IWP2, or the sequestration of Wnt ligands by ext-Fzd8, a decoy receptor containing the extracellular domain of the Wnt co-receptor Frizzled 8. These studies revealed that IWP-2 and ext-Fzd8 could both inhibit ROR1 constitutive phosphorylation and reduce cell motility, but they had no effect on cell growth, indicating that different mechanisms are responsible for the activation of this receptor in neuroblastoma cells. It has been recently reported that the putative tyrosine kinase domain of ROR1 could play a role in the survival of lung cancer cells. We found that the inactivation of ROR1 ATP-binding domain using the CRISPR/Cas9 technology did not affect the growth of SJNB-10 and Kelly cells, implying that the catalytic activity of this receptor is not required for its effects in neuroblastoma cells. In conclusion, we demonstrated that ROR1 can play a dual role in neuroblastoma cell motility and growth through two distinct mechanisms, respectively dependent and independent of noncanonical Wnt ligands, suggesting that this receptor could represent a novel therapeutic target for the treatment of this type of cancer. Citation Format: Alexis Guernet, Sardar Faisal Mahmood, Hassan Ainani, Youssef Anouar, Luca Grumolato. The Wnt noncanonical receptor ROR1 regulates neuroblastoma cell growth and motility through two distinct mechanisms. [abstract]. In: Proceedings of the Fourth AACR International Conference on Frontiers in Basic Cancer Research; 2015 Oct 23-26; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2016;76(3 Suppl):Abstract nr A38.

Human endometrial regenerative cells attenuate renal ischemia reperfusion injury in mice.

BackgroundEndometrial regenerative cells (ERCs) is an attractive novel type of adult mesenchymal stem cells that can be non-invasively obtained from menstrual blood and are easily replicated at a large scale without tumorigenesis. We have previously reported that ERCs exhibit unique immunoregulatory properties in experimental studies in vitro and in vivo. In this study, the protective effects of ERCs on renal ischemia–reperfusion injury (IRI) were examined.MethodsRenal IRI in C57BL/6 mice was induced by clipping bilateral renal pedicles for 30 min, followed by reperfusion for 48 h. ERCs were isolated from healthy female menstrual blood, and were injected (1 million/mouse, i.v.) into mice 2 h prior to IRI induction. Renal function, pathological and immunohistological changes, cell populations and cytokine profiles were evaluated after 48 h of renal reperfusion.ResultsHere, we showed that as compared to untreated controls, administration of ERCs effectively prevented renal damage after IRI, indicated by better renal function and less pathological changes, which were associated with increased serum levels of IL-4, but decreased levels of TNF-α, IFN-γ and IL-6. Also, ERC-treated mice displayed significantly less splenic and renal CD4+ and CD8+ T cell populations, while the percentage of splenic CD4+CD25+ regulatory T cells and infiltrating M2 macrophages in the kidneys were significantly increased in ERC-treated mice.ConclusionsThis study demonstrates that the novel anti-inflammatory and immunoregulatory effects of ERCs are associated with attenuation of renal IRI, suggesting that the unique features of ERCs may make them a promising candidate for cell therapies in the treatment of ischemic acute kidney injury in patients.

Biobanking of Human Mesenchymal Stem Cells: Future Strategy to Facilitate Clinical Applications.

Human mesenchymal stem cells (hMSCs), a type of adult stem cells that hold great potential in clinical applications (e.g., regenerative medicine and cell-based therapy) due to their ability to differentiate into multiple types of specialized cells and secrete soluble factors which can initiate tissue repair and regulate immune response. hMSCs need to be expanded in vitro or cryopreserved to obtain sufficient cell numbers required for clinical applications. However, long-term in vitro culture-expanded hMSCs may raise some biosafety concerns (e.g., chromosomal abnormality and malignant transformation) and compromised functional properties, limiting their use in clinical applications. To avoid those adverse effects, it is essential to cryopreserve hMSCs at early passage and pool them for off-the-shelf use in clinical applications. However, the existing cryopreservation methods for hMSCs have some notable limitations. To address these limitations, several approaches have to be taken in order to produce healthy and efficacious cryopreserved hMSCs for clinical trials, which remains challenging to date. Therefore, a noteworthy amount of resources has been utilized in research in optimization of the cryopreservation methods, development of freezing devices, and formulation of cryopreservation media to ensure that hMSCs maintain their therapeutic characteristics without raising biosafety concerns following cryopreservation. Biobanking of hMSCs would be a crucial strategy to facilitate clinical applications in the future.

Lifespan Extension and Sustained Expression of Stem Cell Phenotype of Human Breast Epithelial Stem Cells in a Medium with Antioxidants.

We have previously reported the isolation and culture of a human breast epithelial cell type with stem cell characteristics (Type I HBEC) from reduction mammoplasty using the MSU-1 medium. Subsequently, we have developed several different normal human adult stem cell types from different tissues using the K-NAC medium. In this study, we determined whether this low calcium K-NAC medium with antioxidants (N-acetyl-L-cysteine and L-ascorbic acid-2-phosphate) is a better medium to grow human breast epithelial cells. The results clearly show that the K-NAC medium is a superior medium for prolonged growth (cumulative population doubling levels ranged from 30 to 40) of normal breast epithelial cells that expressed stem cell phenotypes. The characteristics of these mammary stem cells include deficiency in gap junctional intercellular communication, expression of Oct-4, and the ability to differentiate into basal epithelial cells and to form organoid showing mammary ductal and terminal end bud-like structures. Thus, this new method of growing Type I HBECs will be very useful in future studies of mammary development, breast carcinogenesis, chemoprevention, and cancer therapy.

Cell-cycle quiescence maintains Caenorhabditis elegans germline stem cells independent of GLP-1/Notch.

Many types of adult stem cells exist in a state of cell-cycle quiescence, yet it has remained unclear whether quiescence plays a role in maintaining the stem cell fate. Here we establish the adult germline of Caenorhabditis elegans as a model for facultative stem cell quiescence. We find that mitotically dividing germ cells--including germline stem cells--become quiescent in the absence of food. This quiescence is characterized by a slowing of S phase, a block to M-phase entry, and the ability to re-enter M phase rapidly in response to re-feeding. Further, we demonstrate that cell-cycle quiescence alters the genetic requirements for stem cell maintenance: The signaling pathway required for stem cell maintenance under fed conditions--GLP-1/Notch signaling--becomes dispensable under conditions of quiescence. Thus, cell-cycle quiescence can itself maintain stem cells, independent of the signaling pathway otherwise essential for such maintenance.

Patient-derived mesenchymal stem cells as delivery vehicles for oncolytic virotherapy: novel state-of-the-art technology.

Oncolytic virotherapy is gaining interest in the clinic as a new weapon against cancer. In vivo administration of oncolytic viruses showed important limitations that decrease their effectiveness very significantly: the antiviral immune response causes the elimination of the therapeutic effect, and the poor natural ability of oncolytic viruses to infect micrometastatic lesions significantly minimizes the effective dose of virus. This review will focus on updating the technical and scientific foundations of one of the strategies developed to overcome these limitations, ie, using cells as vehicles for oncolytic viruses. Among many candidates, a special type of adult stem cell, mesenchymal stem cells (MSCs), have already been used in the clinic as cell vehicles for oncolytic viruses, partly due to the fact that these cells are actively being evaluated for other indications. MSC carrier cells are used as Trojan horses loaded with oncoviruses, are administered systemically, and release their cargos at the right places. MSCs are equipped with an array of molecules involved in cell arrest in the capillaries (integrins and selectins), migration toward specific parenchymal locations within tissues (chemokine receptors), and invasion and degradation of the extracellular matrix (proteases). In addition to anatomical targeting capacity, MSCs have a well-recognized role in modulating immune responses by affecting cells of the innate (antigen-presenting cells, natural killer cells) and adaptive immune system (effector and regulatory lymphocytes). Therefore, carrier MSCs may also modulate the immune responses taking place after therapy, ie, the antiviral and the antitumor immune responses.

Evidence of Notch-Hesr-Nrf2 Axis in Muscle Stem Cells, but Absence of Nrf2 Has No Effect on Their Quiescent and Undifferentiated State.

Nrf2 is a master regulator of oxidative stresses through the induction of anti-oxidative genes. Nrf2 plays roles in maintaining murine hematopoietic stem cells and fly intestinal stem cells. The canonical Notch signaling pathway is also crucial for maintaining several types of adult stem cells including muscle stem cells (satellite cells). Here, we show that Dll1 induced Nrf2 expression in myogenic cells. In addition, primary targets of Notch signaling, Hesr1 and Hesr3, were involved in the up-regulation of Nrf2 mRNA and expression of its target genes. In vitro, Nrf2 had anti-myogenic and anti-proliferative effects on primary myoblasts. In vivo, although Nrf2-knockout mice showed decreased expression of its target genes in muscle stem cells, adult muscle stem cells of Nrf2-knockout mice did not exhibit the phenotype. Taken together, in muscle stem cells, the Notch-Hesr-Nrf2 axis is a pathway potentially inducing anti-oxidative genes, but muscle stem cells either do not require Nrf2-mediated anti-oxidative gene expression or they have a complementary system compensating for the loss of Nrf2.

The role of adult tissue-derived stem cells in chronic leg ulcers: a systematic review focused on tissue regeneration medicine.

Wound healing is an articulated process that can be impaired in different steps in chronic wounds. Chronic leg ulcers are a special type of non-healing wounds that represent an important cause of morbidity and public cost in western countries. Because of their common recurrence after conventional managements and increasing prevalence due to an ageing population, newer approaches are needed. Over the last decade, the research has been focused on innovative treatment strategies, including stem-cell-based therapies. After the initial interest in embryonic pluripotent cells, several different types of adult stem cells have been studied because of ethical issues. Specific types of adult stem cells have shown a high potentiality in tissue healing, in both in vitro and in vivo studies. Aim of this review is to clearly report the newest insights on tissue regeneration medicine, with particular regard for chronic leg ulcers.

Concise review: the role of oxygen in hematopoietic stem cell physiology.

Molecular dioxygen, O(2), is an important element in cellular microenvironment in vivo, and often overlooked in standard in vitro and ex vivo cell culture systems. Molecular oxygen is the ultimate electron acceptor in oxidative cellular respiration, and also a signal that regulates cell fate through concentration gradients. Recent advances in physiology of oxygen and adult stem cell research have shown that apart from being important for oxidative phosphorylation, thus energy metabolism, oxygen is also important as a signaling molecule and an integral part of the stem cell niche. This review article covers the influence of physiologically relevant oxygen levels on adult stem cells through highlighting the research on the effect of oxygen concentration on hematopoietic stem cell maintenance, proliferation and differentiation. This is important particularly to understand the embryonic and adult stem cell biology and physiology. The new discoveries in this field will help to further improve current tissue engineering and clinical applications. In addition, understanding the relationship between oxygen and stemness is invaluable for the advanced treatments of neoplastic diseases. Authors believe that in the future, active and programmed dynamic of oxygen levels will be routinely used for the programmed in vitro and ex vivo expansion of different adult stem cell types and tissue regeneration purposes.

Mesenchymal stem cell in vitro labeling by hybrid fluorescent magnetic polymeric particles for application in cell tracking.

Mesenchymal stem cells (MSCs) are a type of adult stem cell that contains multi-differentiation and proliferative properties and that shows high treatment implications for many clinical problems. The outcome of stem cell transplantation is still limited due to many factors, especially their survival and their interaction with the microenvironment after transplantation. Molecular imaging is a challenging technique that has been used to overcome this limitation and is based on the concept of labeling cells with tractable, visible, and non-toxic materials to track the cells after transplantation. In this study, magnetic polymeric nanoparticles (MPNPs) were used to directly label Wharton's jelly-derived MSCs (WJ-MSCs). After labeling, the growth rate and the viability of the MSCs as well as the time of exposure were determined. The 3D images of WJ-MSCs labeled with MPNPs for 24h were created using confocal microscopy. The results showed that, after incubation with fluorescent MPNPs for over 8h, the growth rate and cell viability of the WJ-MSCs was similar to those of the control. Three-dimensional imaging revealed that the fluorescent MPNPs could infiltrate into the cells and spread into the cytoplasm, which suggests that the synthesized fluorescent MPNPs could possibly label MSCs for cell tracking study and be further developed for in vivo applications.

Carboxymethylcellulose (CMC) formed nanogels with branched poly(ethyleneimine) (bPEI) for inhibition of cytotoxicity in human MSCs as a gene delivery vehicles

Specific vehicles are necessary for safe and efficient gene transfection into cells. Nano-type hydrogels (nanogel) comprising carboxymethylcellulose (CMC) complexed with branched type cationic poly(ethleneimine) (bPEI) were used as gene delivery vehicles. When complexes of CMC and bPEI were used in vitro, CMC showed nano-gel type properties, as shown by the results of a viscosity test, and bPEI showed low cytotoxicity comparing to bPEI alone. Together, these properties are shown to maintain high gene transfection efficiency. In viability experiments using three types of adult stem cells, cell viability varied depending on the branch form of PEI and whether or not it is in a complex with CMC. The gene delivery efficacy showed that the CMC nanogel complexed with bPEI (CMC-bPEI) showed more uptaking and gene transfection ability in hMSCs comparing to bPEI alone. In osteogenesis, the CMC-bPEI complexed with OSX pDNA showed more easy internalization than bPEI alone complexed with OSX pDNA in hMSCs. Specific genes and proteins related in osteogenic differentiation were expressed in hMSCs when the CMC-bPEI complexed with OSX pDNA was used.

Urine-Derived Stem Cells for Tissue Repair in the Genitourinary System

Tissue-specific stem cells can more efficiently repair the tissue from which they originate, compared to other types of adult stem cells. Human urine-derived stem cells (USCs), a subpopulation of cells constantly exposed to urine, possess biological characteristics of stem cells, and thus are an optimal cell source for tissue repair in the genitourinary system. USCs display clonogenicity, high proliferation capacity, stem cell marker expression profiles, and multipotent differentiation capacity. These cells can more efficiently differentiate into the cell types of the genitourinary tract, particular in urothelial cells, renal podocytes, and endothelial cells, compared to other adult stem cells. In addition, USCs secrete numerous growth factors and cytokines to support cell growth, differentiation, resident stem cell recruitment, and immunomodulatory properties. In vivo studies in rodent models of diabetic erectile dysfunction, urinary tract incontinence, and renal dysfunction demonstrated that USCs significantly enhanced organ function via angiogenesis and transdifferentiation, and showed anti-inflammatory and anti-fibrotic properties after implantation of USCs. USCs can be obtained via a simple, non-invasive, and low-cost approach. Thus, USCs offer an extremely promising cell source for cell-based therapy in androurology.