Stem cell therapy in pain medicine

Yong Hee Han,Kyung Hoon Kim,Salahadin Abdi,Tae Kyun Kim 대한통증학회 2019 The Korean Journal of Pain Vol.32 No.4

Stem cells are attracting attention as a key element in future medicine, satisfying the desire to live a healthier life with the possibility that they can regenerate tissue damaged or degenerated by disease or aging. Stem cells are defined as undifferentiated cells that have the ability to replicate and differentiate themselves into various tissues cells. Stem cells, commonly encountered in clinical or preclinical stages, are largely classified into embryonic, adult, and induced pluripotent stem cells. Recently, stem cell transplantation has been frequently applied to the treatment of pain as an alternative or promising approach for the treatment of severe osteoarthritis, neuropathic pain, and intractable musculoskeletal pain which do not respond to conventional medicine. The main idea of applying stem cells to neuropathic pain is based on the ability of stem cells to release neurotrophic factors, along with providing a cellular source for replacing the injured neural cells, making them ideal candidates for modulating and possibly reversing intractable neuropathic pain. Even though various differentiation capacities of stem cells are reported, there is not enough knowledge and technique to control the differentiation into desired tissues in vivo. Even though the use of stem cells is still in the very early stages of clinical use and raises complicated ethical problems, the future of stem cells therapies is very bright with the help of accumulating evidence and technology.

Evaluation of the maintenance of stemness, viability, and differentiation potential of gingiva-derived stem-cell spheroids

Lee, Sung-Il,Ko, Youngkyung,Park, Jun-Beom D.A. Spandidos 2017 Experimental and therapeutic medicine Vol.13 No.5

<P>Gingiva-derived stem cells have been applied for tissue-engineering purposes and may be considered a favorable source of mesenchymal stem cells as harvesting stem cells from the mandible or maxilla may be performed with ease under local anesthesia. The present study was performed to fabricate stem-cell spheroids using concave microwells and to evaluate the maintenance of stemness, viability, and differentiation potential. Gingiva-derived stem cells were isolated, and the stem cells of 4×10<SUP>5</SUP> (group A) or 8×10<SUP>5</SUP> (group B) cells were seeded into polydimethylsiloxane-based, concave micromolds with 600 µm diameters. The morphology of the microspheres and the change of the diameters of the spheroids were evaluated. The viability of spheroids was qualitatively analyzed via Live/Dead kit assay. A cell viability analysis was performed on days 1, 3, 6, and 12 with Cell Counting Kit-8. The maintenance of stemness was evaluated with immunocytochemical staining using SSEA-4, TRA-1-60(R) (positive markers), and SSEA-1 (negative marker). Osteogenic, adipogenic, and chondrogenic differentiation potential was evaluated by incubating spheroids in osteogenic, adipogenic and chondrogenic induction medium, respectively. The gingiva-derived stem cells formed spheroids in the concave microwells. The diameters of the spheroids were larger in group A than in group B. The majority of cells in the spheroids emitted green fluorescence, indicating the presence of live cells at day 6. At day 12, the majority of cells in the spheroids emitted green fluorescence, and a small portion of red fluorescence was also noted, which indicated the presence of dead cells. The spheroids were positive for the stem-cell markers SSEA-4 and TRA-1-60(R) and were negative for SSEA-1, suggesting that these spheroids primarily contained undifferentiated human stem cells. Osteogenic, adipogenic, and chondrogenic differentiation was more evident with an increase of incubation time: Mineralized extracellular deposits were observed following Alizarin Red S staining at days 14 and 21; oil globules were increased at day 18 when compared with day 6; and Alcian blue staining was more evident at day 18 when compared with day 6. Within the limits of this study, stem-cell spheroids from gingival cells maintained the stemness, viability, and differentiation potential during the experimental periods. This method may be applied for a promising strategy for stem-cell therapy.</P>

Nuclear receptor regulation of stemness and stem cell differentiation

David J. Mangelsdorf,정양식 생화학분자생물학회 2009 Experimental and molecular medicine Vol.41 No.8

Stem cells include a diverse number of toti-, pluri-, and multi-potent cells that play important roles in cellular genesis and differentiation, tissue development, and organogenesis. Genetic regulation involving various transcription factors results in the self-renewal and differentiation properties of stem cells. The nuclear receptor (NR) superfamily is composed of 48 ligand-activated transcription factors involved in diverse physiological functions such as metabolism, development, and reproduction. Increasing evidence shows that certain NRs function in regulating stemness or differentiation of embryonic stem (ES) cells and tissue-specific adult stem cells. Here, we review the role of the NR superfamily in various aspects of stem cell biology, including their regulation of stemness, forward- and trans-differentiation events; reprogramming of terminally differentiated cells; and interspecies differences. These studies provide insights into the therapeutic potential of the NR superfamily in stem cell therapy and in treating stem cell-associated diseases (e.g., cancer stem cell). Stem cells include a diverse number of toti-, pluri-, and multi-potent cells that play important roles in cellular genesis and differentiation, tissue development, and organogenesis. Genetic regulation involving various transcription factors results in the self-renewal and differentiation properties of stem cells. The nuclear receptor (NR) superfamily is composed of 48 ligand-activated transcription factors involved in diverse physiological functions such as metabolism, development, and reproduction. Increasing evidence shows that certain NRs function in regulating stemness or differentiation of embryonic stem (ES) cells and tissue-specific adult stem cells. Here, we review the role of the NR superfamily in various aspects of stem cell biology, including their regulation of stemness, forward- and trans-differentiation events; reprogramming of terminally differentiated cells; and interspecies differences. These studies provide insights into the therapeutic potential of the NR superfamily in stem cell therapy and in treating stem cell-associated diseases (e.g., cancer stem cell).

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.

Stem cell therapy in pain medicine

Han, Yong Hee,Kim, Kyung Hoon,Abdi, Salahadin,Kim, Tae Kyun The Korean Pain Society 2019 The Korean Journal of Pain Vol.32 No.4

Stem cells are attracting attention as a key element in future medicine, satisfying the desire to live a healthier life with the possibility that they can regenerate tissue damaged or degenerated by disease or aging. Stem cells are defined as undifferentiated cells that have the ability to replicate and differentiate themselves into various tissues cells. Stem cells, commonly encountered in clinical or preclinical stages, are largely classified into embryonic, adult, and induced pluripotent stem cells. Recently, stem cell transplantation has been frequently applied to the treatment of pain as an alternative or promising approach for the treatment of severe osteoarthritis, neuropathic pain, and intractable musculoskeletal pain which do not respond to conventional medicine. The main idea of applying stem cells to neuropathic pain is based on the ability of stem cells to release neurotrophic factors, along with providing a cellular source for replacing the injured neural cells, making them ideal candidates for modulating and possibly reversing intractable neuropathic pain. Even though various differentiation capacities of stem cells are reported, there is not enough knowledge and technique to control the differentiation into desired tissues in vivo. Even though the use of stem cells is still in the very early stages of clinical use and raises complicated ethical problems, the future of stem cells therapies is very bright with the help of accumulating evidence and technology.

줄기세포의 개요

허용준,김동욱 대한의사협회 2011 대한의사협회지 Vol.54 No.5

We are now in the middle of stem cell war. Each country is trying to invest a large amount of funds into stem cell research. This is due to a potentiality of stem cells. Stem cells are capable of proliferating in an undifferentiated manner and are able to differentiate into a desired cell lineage under certain conditions. These abilities make stem cells an appealing source for cell replacement therapies (regenerative medicine), the study of developmental biology and drug/toxin screening. In addition to embryonic and adult stem cells, induced pluripotent stem (iPS) cells has been recently generated through reprogramming from adult tissue cells such as fibroblasts. This technique has opened up new avenues to generate patient- and disease-specific pluripotent stem cells. Human iPS cells may be useful for gaining valuable insight into the pathophysiology of disease, as well as for discovering for new prognostic biomarkers and drug screening. Moreover,the iPS cell technology may play a major role in immune-matched clinical application in the future. In this chapter, we introduce general characteristics of various stem cells, clinical application of stem cells and future perspectives.

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.

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.

Comparative Characterization of Skeletal Stem Cells from Various Tissues

( Whee Moon Cho ),( Seung Woo Nam ),( Eun Ah Lee ),( Young Sook Son ) 한국조직공학과 재생의학회 2010 조직공학과 재생의학 Vol.7 No.3

Tissue engineering is an approach to repair damaged or defected tissue with stem cells and scaffolds. Stem cells used in tissue engineering can be easily expanded in vitro, and can be differentiate to other cell types. To secure the various sources of stem/progenitor cells, stromal cells from various tissues were isolated and characterized. Bone marrow stormal cells (BMSCs), also known as mesenchymal stem cells, can differentiate into other cell types and they are best in their utilization potential among many skeletal stem cells. Various musculoskeletal tissues such as adipose, xiphisternum cartilage, tendon, and ligament contain stromal cells, which can be isolated using collagenase type I. Isolated cells were named as Adipose derived stem cells (ADSCs), xiphisternum derived stem cells (XDSCs), tendon derived stem cells (TDSCs), and ligament derived stem cells. Although it is probable that every isolated stem cells displayed different characteristics, there has been no approach to compare those cells in exactly same conditions. In this study, various tissue derived stem cells were comparatively characterized for the cell morphology, colony morphology, CFU-F, and surface marker expressions. Stem cells derived from various tissues displayed morphology of fibroblast-like shape, although there were subtle differences between the skeletal stem cells according to their origin. Based on CFU-F assay, all the cells showed density-independent growth when they were seeded in clonogenic density. All the stem cells tested showed positive expression of CD90 and α-SMA and negative to CD45 displaying similar characteristics to BMSCs.