• Clinical and Experimental Otorhinolaryngology
• /
• 제11권4호
• /
• pp.224-232
• /
• 2018

Objectives. Spiral ganglion neurons (SGNs) include potential endogenous progenitor populations for the regeneration of the peripheral auditory system. However, whether these populations are present in adult mice is largely unknown. We examined the presence and characteristics of SGN-neural stem cells (NSCs) in mice as a function of age. Methods. The expression of Nestin and Ki67 was examined in sequentially dissected cochlear modiolar tissues from mice of different ages (from postnatal day to 24 weeks) and the sphere-forming populations from the SGNs were isolated and differentiated into different cell types. Results. There were significant decreases in Nestin and Ki67 double-positive mitotic progenitor cells in vivo with increasing mouse age. The SGNs formed spheres exhibiting self-renewing activity and multipotent capacity, which were seen in NSCs and were capable of differentiating into neuron and glial cell types. The SGN spheres derived from mice at an early age (postnatal day or 2 weeks) contained more mitotic stem cells than those from mice at a late age. Conclusion. Our findings showed the presence of self-renewing and proliferative subtypes of SGN-NSCs which might serve as a promising source for the regeneration of auditory neurons even in adult mice.

• Korean Journal of Otorhinolaryngology-Head and Neck Surgery
• /
• 제56권12호
• /
• pp.749-753
• /
• 2013

Basically stem cells have characteristics of multi-potency, differentiation into multiple tissue types, and self-renew through proliferation. Recent advances in stem cell biology can make identifying the stem-cell like cells in various mammalian tissues. Stem cells in various tissues can restore damaged tissue. Stem cells from the adult nervous system proliferate to form clonal floating colonies called spheres in vitro, and recent studies have demonstrated sphere formation by cells in the tympanic membrane, vestibular system, spiral ganglion, and partly in the organ of Corti. The presence of stem cells in the ear raises the possibilities for the regeneration of the tympanic membrane & inner ear hair cells & neurons. But the gradual loss of stem cells postnatally in the organ of Corti may correlate with the loss of regenerative capacity and limited hearing restoration. Future strategies using endogenous stem cells in the ear can be the another treatment modality for the patients with intractable inner ear diseases.

• BMB Reports
• /
• 제50권6호
• /
• pp.285-298
• /
• 2017

The cancer stem cell (CSC) hypothesis has captured the attention of many scientists. It is believed that elimination of CSCs could possibly eradicate the whole cancer. CSC surface markers provide molecular targeted therapies for various cancers, using therapeutic antibodies specific for the CSC surface markers. Various CSC surface markers have been identified and published. Interestingly, most of the markers used to identify CSCs are derived from surface markers present on human embryonic stem cells (hESCs) or adult stem cells. In this review, we classify the currently known 40 CSC surface markers into 3 different categories, in terms of their expression in hESCs, adult stem cells, and normal tissue cells. Approximately 73% of current CSC surface markers appear to be present on embryonic or adult stem cells, and they are rarely expressed on normal tissue cells. The remaining CSC surface markers are considerably expressed even in normal tissue cells, and some of them have been extensively validated as CSC surface markers by various research groups. We discuss the significance of the categorized CSC surface markers, and provide insight into why surface markers on hESCs are an attractive source to find novel surface markers on CSCs.

• Molecules and Cells
• /
• 제43권2호
• /
• pp.121-125
• /
• 2020

The identification of adult stem cells is challenging because of the heterogeneity and plasticity of stem cells in different organs. Within the same tissue, stem cells may be highly proliferative, or maintained in a quiescent state and only to be activated after tissue damage. Although various stem cell markers have been successfully identified, there is no universal stem cell marker, which is exclusively expressed in all stem cells. Here, we discuss the roles of master developmental regulator RUNX1 in stem cells and the development of a 270 base pair fragment of the Runx1 enhancer (eR1) for use as stem cell marker. Using eR1 to identify stem cells offers a distinct advantage over gene promoters, which might not be expressed exclusively in stem cells. Moreover, RUNX1 has been strongly implicated in various cancer types, such as leukemia, breast, esophageal, prostate, oral, skin, and ovarian cancers-it has been suggested that RUNX1 dysfunction promotes stem cell dysfunction and proliferation. As tissue stem cells are potential candidates for cancer cells-of-origin and cancer stem cells, we will also discuss the use of eR1 to target oncogenic gene manipulations in stem cells and to track subsequent neoplastic changes.

• Maxillofacial Plastic and Reconstructive Surgery
• /
• 제30권2호
• /
• pp.133-141
• /
• 2008

Stem cells have self-renewal capacity, long-term viability, and multiline age potential. Adult bone marrow contains mesenchymal stem cells. Bone marrow-derived mesenchymal stem cells (BMSCs) are progenitors of skeletal tissue components and can differentiate into adipocytes, chondrocytes, osteoblasts, and myoblasts in vitro and undergo differentiation in vivo. However, the clinical use of BMSCs has presented problems, including pain, morbidity, and low cell number upon harvest. Recent studies have identified a putative stem cell population within the adipose tissue. Human adipose tissue contains pluripotent stem cells simillar to bone marrow-derived stem cells that can differentiate toward the osteogenic, adipogenic, myogenic, and chondrogenic lineages. Human adipose tissue-derived stem cells (ATSCs) could be proposed as an alternative source of adult bone marrow stem cells, and could be obtained in large quantities, under local anesthesia, with minimal discomfort. Human adipose tissue obtained by liposuction was processed to obtain ATSCs. In this study, we compared the osteogenic differentiation of ATSCs in a specific osteogenic induction medium with that in a non-osteogenic medium. ATSCs were incubated in an osteogenic medium for 28 days to induce osteogenesis respectively. Osteogenic differentiation was assessed by von Kossa and alkaline phosphatase staining. Expression of osteocyte specific bone sialoprotein, osteocalcin, collagen type I and alkaline phosphatase, bone morphogenic protein 2, bone morphogenic protein 6 was confirmed by RT-PCR. ATSCs incubated in the osteogenic medium were stained positively for von Kossa and alkaline phosphatase staining. Expression of osteocyte specific genes was also detected. Since this cell population can be easily identified through fluorescence microscopy, it may be an ideal source of ATSCs for further experiments on stem cell biology and tissue engineering. The present results show that ADSCs have an ability to differentiate into osteoblasts. In the present study, we extend this approach to characterize adipose tissue-derived stem cells.

• Molecules and Cells
• /
• 제21권3호
• /
• pp.343-355
• /
• 2006

Stem cells are unique cell populations with the ability to undergo both self-renewal and differentiation, although a wide variety of adult stem cells as well as embryonic stem cells have been identified and stem cell plasticity has recently been reported. To identify genes implicated in the control of the stem cell state as well as the characteristics of each stem cell line, we analyzed the expression profiles of genes in human embryonic, hematopoietic ($CD34^+$ and $CD133^+$), and mesenchymal stem cells using cDNA microarrays, and identified genes that were differentially expressed in specific stem cell populations. In particular we were able to identify potential hESC signature-like genes that encode transcription factors (TFAP2C and MYCN), an RNA binding protein (IMP-3), and a functionally uncharacterized protein (MAGEA4). The overlapping sets of 22 up-regulated and 141 down-regulated genes identified in this study of three human stem cell types may also provide insight into the developmental mechanisms common to all human stem cells. Furthermore, our comprehensive analyses of gene expression profiles in various adult stem cells may help to identify the genetic pathways involved in self-renewal as well as in multi-lineage specific differentiation.

• Journal of Korean Neurosurgical Society
• /
• 제63권2호
• /
• pp.153-162
• /
• 2020

Spinal cord injury (SCI) is one of the most devastating conditions and many SCI patients suffer neurological sequelae. Stem cell therapies are expected to be beneficial for many patients with central nervous system injuries, including SCI. Adult stem cells (ASCs) are not associated with the risks which embryonic stem cells have such as malignant transformation, or ethical problems, and can be obtained relatively easily. Consequently, many researchers are currently studying the effects of ASCs in clinical trials. The environment of transplanted cells applied in the injured spinal cord differs between the phases of SCI; therefore, many researchers have investigated these phases to determine the optimal time window for stem cell therapy in animals. In addition, the results of clinical trials should be evaluated according to the phase in which stem cells are transplanted. In general, the subacute phase is considered to be optimal for stem cell transplantation. Among various candidates of transplantable ASCs, mesenchymal stem cells (MSCs) are most widely studied due to their clinical safety. MSCs are also less immunogenic than neural stem/progenitor cells and consequently immunosuppressants are rarely required. Attempts have been made to enhance the effects of stem cells using scaffolds, trophic factors, cytokines, and other drugs in animal and/or human clinical studies. Over the past decade, several clinical trials have suggested that transplantation of MSCs into the injured spinal cord elicits therapeutic effects on SCI and is safe; however, the clinical effects are limited at present. Therefore, new therapeutic agents, such as genetically enhanced stem cells which effectively secrete neurotrophic factors or cytokines, must be developed based on the safety of pure MSCs.

• BMB Reports
• /
• 제57권4호
• /
• pp.182-187
• /
• 2024

Neural stem cells (NSCs) in the adult hippocampus divide infrequently; the endogenous molecules modulating adult hippocampal neurogenesis (AHN) remain largely unknown. Here, we show that ErbB3 binding protein 1 (Ebp1), which plays important roles in embryonic neurodevelopment, acts as an essential modulator of adult neurogenic factors. In vivo analysis of Ebp1 neuron depletion mice showed impaired AHN with a low number of hippocampal NSCs and neuroblasts. Ebp1 leads to transcriptional repression of Bmp4 and suppression of Ascl1 promoter methylation in the dentate gyrus of the adult hippocampus reflecting an unusually high level of Bmp4 and low Ascl1 level in neurons of Ebp1-deficient mice. Therefore, our findings suggests that Ebp1 could act as an endogenous modulator of the interplay between Bmp4 and Ascl1/Notch signaling, contributing to AHN.

• Journal of Veterinary Science
• /
• 제22권1호
• /
• pp.7.1-7.13
• /
• 2021

Background: Niemann-Pick disease type C (NPC) is caused by the mutation of NPC genes, which leads to the abnormal accumulation of unesterified cholesterol and glycolipids in lysosomes. This autosomal recessive disease is characterized by liver dysfunction, hepatosplenomegaly, and progressive neurodegeneration. Recently, the application of induced neural stem cells (iNSCs), converted from fibroblasts using specific transcription factors, to repair degenerated lesions has been considered a novel therapy. Objectives: The therapeutic effects on NPC by human iNSCs generated by our research group have not yet been studied in vivo; in this study, we investigate those effects. Methods: We used an NPC mouse model to efficiently evaluate the therapeutic effect of iNSCs, because neurodegeneration progress is rapid in NPC. In addition, application of human iNSCs from NPC patient-derived fibroblasts in an NPC model in vivo can give insight into the clinical usefulness of iNSC treatment. The iNSCs, generated from NPC patientderived fibroblasts using the SOX2 and HMGA2 reprogramming factors, were transplanted by intracerebral injection into NPC mice. Results: Transplantation of iNSCs showed positive results in survival and body weight change in vivo. Additionally, iNSC-treated mice showed improved learning and memory in behavior test results. Furthermore, through magnetic resonance imaging and histopathological assessments, we observed delayed neurodegeneration in NPC mouse brains. Conclusions: iNSCs converted from patient-derived fibroblasts can become another choice of treatment for neurodegenerative diseases such as NPC.

• 한국발생생물학회:학술대회논문집
• /
• 한국발생생물학회 2009년도 특별 Symposium
• /
• pp.34-34
• /
• 2009