혈액질환치료에 있어 동종말초조혈모세포와 배양확장된 간엽모세포(Mesenchymal Stem Cell)의 동시이식 2예

강석윤,김재홍,박준성,김현수,최진혁,임호영,양말숙,김영진,김효철 대한조혈모세포이식학회 2001 대한조혈모세포이식학회지 Vol.6 No.1

Human bone marrow contain two kinds of stem cells. One is hematopoietic stem cell, and the other is multipotential mesenchymal stem cells which are capable of differentiating into a number of mesenchymal cell lineages. These mesenchymal stem cells are shown to secrete hematopoietic cytokines and support hematopietic progenitors in vitro. Animal models suggest that the transplantation of healthy stromal elements, including mesenchymal stem cells, may enhance the ability of the bone marrow microenvironment to support hematopoiesis after stem cell transplantation. Therefore, We hypothesized that cotransplantation of hematopoietic stem cells and mesenchymal stem cells after high dose chemotherapy would facilitate engraftment of hematopietic stem cells and reduce complications caused by delayed engraftments. And we investigated the safety, feasibility, side effects and hematopoietic effects of in vitro-expanded mesenchymal stem cells in hematologic malignancies receiving allogeneic peripheral stem cell transplantation.

Bone Formation of Embryonic Stem Cell-Derived Mesenchymal Stem Cells

정연태,유기연,이희수 한국조직공학과 재생의학회 2015 조직공학과 재생의학 Vol.12 No.4

Human embryonic stem cells are multipotent cells. In this study, We observed osteogenesis of human embryonic stem cell derived mesenchymal stem cells. mbryonic body formation method was used to derive mesenchymal stem cells from human embryonic stem cells. Embryonic stem cell derived mesenchymal stem cells were immunostained for CD 73 to make characterization of mesencymal stem cells. Osteogenesis of CD 73 positive mesencymal stem cells with media included ascorbic acid, dexamethasone and glycerophosphate was induced. After 10 days culture with osteogenesis media, the cells were immunostained with type I collagen, osteocalcin and Runx-2. After 21 days culture with osteogenesis media, the cells were stained with alizarin red to observe bone nodule formation. Mesenchymal stem cells were derived from human embryonic stem cells by embryonic body method. After these cells were cultured with osteogenesis media, the cells were differentiated into osteoblast and showed bone nodule formation.

Bone Formation of Embryonic Stem Cell-Derived Mesenchymal Stem Cells

( Yeon Tae Jung ),( Ki Yeon Yoo ),( Hee Su Lee ) 한국조직공학·재생의학회 2015 조직공학과 재생의학 Vol.12 No.2s

Human embryonic stem cells are multipotent cells. In this study, We observed osteogenesis of human embryonic stem cell derived mesenchymal stem cells. mbryonic body formation method was used to derive mesenchymal stem cells from human embryonic stem cells. Embryonic stem cell derived mesenchymal stem cells were immunostained for CD 73 to make characterization of mesencymal stem cells. Osteogenesis of CD 73 positive mesencymal stem cells with media included ascorbic acid, dexamethasone and glycerophosphate was induced. After 10 days culture with osteogenesis media, the cells were immunostained with type I collagen, osteocalcin and Runx-2. After 21 days culture with osteogenesis media, the cells were stained with alizarin red to observe bone nodule formation. Mesenchymal stem cells were derived from human embryonic stem cells by embryonic body method. After these cells were cultured with osteogenesis media, the cells were differentiated into osteoblast and showed bone nodule formation. Tissue Eng Regen Med 2015;12(Suppl 2):132-137

Profiling of Differentially Expressed Genes in Human Stem Cells by cDNA Microarray

김철근,이종주,정대영,전진선,허현석,강호철,신준호,조윤신,차경준,김찬길,도병록,김경숙,김현수 한국분자세포생물학회 2006 Molecules and cells Vol.21 No.3

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 downregulated 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.

줄기세포 기반의 치주조직재생

박재욱,박주철 대한구강해부학회 2014 대한구강해부학회지 Vol.35 No.1

Periodontium is complex tissue composed of cementum, periodontal ligament and alveolar bone which holds the tooth in the bone. periodontitis is main cause of tooth loss leads to loss of attachment of connective tissue and irreversible bony destruction. So periodontitis has been one of the main concern to dentist, patient and oral health system. For recent years the main purpose of periodontics is regeneration of damaged peroidontium on shape, structure and function. In periodontal regeneration, new connective tissue fibers should be inserted in the cementum and bone, and construct the complex cementum-ligament-bone interfaces and provide a functional connection between a tooth and the surrounding jaw. Recently, many surgical, nonsurgical therapies and bone substitutes are using, but the clinical outcomes are still limiting. Bone transplantation or bone substitutes like guided bone regeneration, guided tissue regeneration don't have the capacity to regenerate destructed connective tissue. With cell based therapy, numerous growth factors and modulating agents have used but it made limited success. Stem cell based therapy is the most active researching field in medical and dental area. However, when diseased periodontal condition, tissue repair does not occur naturally because of the lack of sound stem cells. So exogenous regenerative tools such as ex vivo expanded/ manipulated stem cells will be needed to replenish the host cell niche and facililtate tissue regeneration. As the increasing success of regenerating other tissues(skin, cartilage, bone, cardiovascular component, pancreas), stem cell based periodontal regeneration with tissue engineering approach can be new field of treatment. Comparing stem cells from other sites of adult body, dental stem cells have advantage that is easy access to gaining site and have characteristics like proliferation, differentiation, and flexiblity. Some kind of reviewed stem cells, dental pulp stem cells (DPSCs), Stem cells from exfoliated deciduous teeth (SHED), PDL stem cells (PDLSCs), Stem cells from apical papilla, apical papilla stem cells (SCAP), Dental follicle cells (DFCs), and MSCs are most actively studied for stem cell based periodontal regeneration. However, safety problems are not completely examined, and the difficulty of ex vivo proliferation is still recognized to limiatation of stem cells. With effective stem cell delivery strategy, research to overcome these limitations should be continued. With recent advancement of stem cell based periodontal tissue engineering and periodontal regeneration, next step of research should be concentrated to clinical application of this advanced therapeutic method. Accordingly, further studies are required to develop new methods to identify and maintain multipotent stem cells in vitro and to determine the long term safety and efficacy of ex vivo expanded stem cells to repair periodontal defects in large animal models. With partial regeneration of tooth, whole tooth regeneration has been actively studied. When whole tooth regeneration succeed, regenerating periodontal ligament and contact of tooth-periodontium are needed to transplant regenerated tooth. So periodontal regeneration is essential step to achieve whole tooth regeneration and replantation.

줄기세포 치료의 허와 실

오일환 대한의사협회 2013 대한의사협회지 Vol.56 No.10

Stem cell therapy has been taken as a highly promising area of future medicine due to its potential for providing new therapeutic modalities for debilitating, incurable diseases. In addition, stem cell therapy holds promise for its great industrial value due to the rapid growth of the market size. Recently, various types of stem cells such as induced pluripotent stem cells are being developed based on the conceptual revolution with regard to cell fate decisions. However, so far, most stem cell therapies have been performed using tissue-specific adult stem cells. Nevertheless, except for a few cases of stem cells such as hematopoietic stem cells that can regenerate hematopoietic tissue, a large proportion of stem cells, especially mesenchymal stromal cells, primarily work through paracrine functioning. The short life span of the injected stem cells and their paracrine mode of action pose a limitation to the maximum therapeutic efficacy that can be achieved from the current stem cell therapy model, warranting further research and development to enhance their efficacy. Despite the fact that stem cell therapies largely remain in the research stage, the public has expectations of rapid results and even fanaticism, leading to unauthorized stem cell practices and medical tourism. Moreover, the temptation to expedite the industrialization of stem cell therapeutics by simplifying the authorization process could increase the risk of endangering the rights of patients. Thus, stem cell therapy can become a ‘hope’ when society can overcome the stem cell ‘hype’.

Gene expression profile in mesenchymal stem cells derived from dental tissues and bone marrow

Kim, Su-Hwan,Kim, Young-Sung,Lee, Su-Yeon,Kim, Kyoung-Hwa,Lee, Yong-Moo,Kim, Won-Kyung,Lee, Young-Kyoo Korean Academy of Periodontology 2011 Journal of Periodontal & Implant Science Vol.41 No.4

Purpose: The aim of this study is to compare the gene expression profile in mesenchymal stem cells derived from dental tissues and bone marrow for characterization of dental stem cells. Methods: We employed GeneChip analysis to the expression levels of approximately 32,321 kinds of transcripts in 5 samples of bone-marrow-derived mesenchymal stem cells (BMSCs) (n=1), periodontal ligament stem cells (PDLSCs) (n=2), and dental pulp stem cells (DPSCs) (n=2). Each cell was sorted by a FACS Vantage Sorter using immunocytochemical staining of the early mesenchymal stem cell surface marker STRO-1 before the microarray analysis. Results: We identified 379 up-regulated and 133 down-regulated transcripts in BMSCs, 68 up-regulated and 64 down-regulated transcripts in PDLSCs, and 218 up-regulated and 231 down-regulated transcripts in DPSCs. In addition, anatomical structure development and anatomical structure morphogenesis gene ontology (GO) terms were over-represented in all three different mesenchymal stem cells and GO terms related to blood vessels, and neurons were over-represented only in DPSCs. Conclusions: This study demonstrated the genome-wide gene expression patterns of STRO-$1^+$ mesenchymal stem cells derived from dental tissues and bone marrow. The differences among the expression profiles of BMSCs, PDLSCs, and DPSCs were shown, and 999 candidate genes were found to be definitely up- or down-regulated. In addition, GOstat analyses of regulated gene products provided over-represented GO classes. These data provide a first step for discovering molecules key to the characteristics of dental stem cells.

Gene expression profile in mesenchymal stem cells derived from dental tissues and bone marrow

김수환,김영성,이수연,김경화,이용무,김원경,이영규 대한치주과학회 2011 Journal of Periodontal & Implant Science Vol.41 No.4

Purpose: The aim of this study is to compare the gene expression profile in mesenchymal stem cells derived from dental tissues and bone marrow for characterization of dental stem cells. Methods: We employed GeneChip analysis to the expression levels of approximately 32,321 kinds of transcripts in 5 samples of bone-marrow-derived mesenchymal stem cells (BMSCs) (n=1), periodontal ligament stem cells (PDLSCs) (n=2), and dental pulp stem cells (DPSCs) (n=2). Each cell was sorted by a FACS Vantage Sorter using immunocytochemical staining of the early mesenchymal stem cell surface marker STRO-1 before the microarray analysis. Results: We identified 379 up-regulated and 133 down-regulated transcripts in BMSCs, 68 up-regulated and 64 down-regulated transcripts in PDLSCs, and 218 up-regulated and 231 down-regulated transcripts in DPSCs. In addition, anatomical structure development and anatomical structure morphogenesis gene ontology (GO) terms were over-represented in all three different mesenchymal stem cells and GO terms related to blood vessels, and neurons were over-represented only in DPSCs. Conclusions: This study demonstrated the genome-wide gene expression patterns of STRO-1+ mesenchymal stem cells derived from dental tissues and bone marrow. The differences among the expression profiles of BMSCs, PDLSCs, and DPSCs were shown, and 999 candidate genes were found to be definitely up- or down-regulated. In addition, GOstat analyses of regulated gene products provided over-represented GO classes. These data provide a first step for discovering molecules key to the characteristics of dental stem cells.

Current Status and Future Strategies to Treat Spinal Cord Injury with Adult Stem Cells

Jeong, Seong Kyun,Choi, Il,Jeon, Sang Ryong The Korean Neurosurgical Society 2020 Journal of Korean neurosurgical society Vol.63 No.2

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.

Adult Stem Cell Therapy for Stroke: Challenges and Progress

방오영,김은희,차재민,문경준 대한뇌졸중학회 2016 Journal of stroke Vol.18 No.3

Stroke is one of the leading causes of death and physical disability among adults. It has been 15 years since clinical trials of stem cell therapy in patients with stroke have been conducted using adult stem cells like mesenchymal stem cells and bone marrow mononuclear cells. Results of randomized controlled trials showed that adult stem cell therapy was safe but its efficacy was modest, underscoring the need for new stem cell therapy strategies. The primary limitations of current stem cell therapies include (a) the limited source of engraftable stem cells, (b) the presence of optimal time window for stem cell therapies, (c) inherited limitation of stem cells in terms of growth, trophic support, and differentiation potential, and (d) possible transplanted cell-mediated adverse effects, such as tumor formation. Here, we discuss recent advances that overcome these hurdles in adult stem cell therapy for stroke.