1.Stem cell therapy in pain medicine
Yong Hee HAN ; Kyung Hoon KIM ; Salahadin ABDI ; Tae Kyun KIM
The Korean Journal of Pain 2019;32(4):245-255
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.
Adult
;
Adult Stem Cells
;
Aging
;
Cell Differentiation
;
Embryonic Stem Cells
;
Humans
;
Induced Pluripotent Stem Cells
;
Musculoskeletal Pain
;
Nerve Growth Factors
;
Neuralgia
;
Osteoarthritis
;
Stem Cell Transplantation
;
Stem Cells
2.Stem Cell-Based Therapies for Liver Diseases: An Overview and Update
Jie WANG ; Meiyan SUN ; Wei LIU ; Yan LI ; Miao LI
Tissue Engineering and Regenerative Medicine 2019;16(2):107-118
BACKGROUND: Liver disease is one of the top causes of death globally. Although liver transplantation is a very effective treatment strategy, the shortage of available donor organs, waiting list mortality, and high costs of surgery remain huge problems. Stem cells are undifferentiated cells that can differentiate into a variety of cell types. Scientists are exploring the possibilities of generating hepatocytes from stem cells as an alternative for the treatment of liver diseases. METHODS: In this review, we summarized the updated researches in the field of stem cell-based therapies for liver diseases as well as the current challenges and future expectations for a successful cell-based liver therapy. RESULTS: Several cell types have been investigated for liver regeneration, such as embryonic stem cells, induced pluripotent stem cells, liver stem cells, mesenchymal stem cells, and hematopoietic stem cells. In vitro and in vivo studies have demonstrated that stem cells are promising cell sources for the liver regeneration. CONCLUSION: Stem cell-based therapy could be a promising therapeutic method for patients with end-stage liver disease, which may alleviate the need for liver transplantation in the future.
Cause of Death
;
Embryonic Stem Cells
;
Hematopoietic Stem Cells
;
Hepatocytes
;
Humans
;
In Vitro Techniques
;
Induced Pluripotent Stem Cells
;
Liver Diseases
;
Liver Regeneration
;
Liver Transplantation
;
Liver
;
Mesenchymal Stromal Cells
;
Methods
;
Mortality
;
Stem Cells
;
Tissue Donors
;
Waiting Lists
3.Regenerative Medicine of the Bile Duct: Beyond the Myth
Elina Maria BUISSON ; Jaemin JEONG ; Han Joon KIM ; Dongho CHOI
International Journal of Stem Cells 2019;12(2):183-194
Cholangiopathies are rare diseases of the bile duct with high mortality rates. The current treatment for cholangiopathies is liver transplantation, but there are significant obstacles including a shortage of donors and a high risk of complications. Currently, there is only one available medicine on the market targeting cholangiopathies, and the results have been inadequate in clinical therapy. To overcome these obstacles, many researchers have used human induced pluripotent stem cells (hPSC) as a source for cholangiocyte-like cell generation and have incorporated advances in bioprinting to create artificial bile ducts for implantation and transplantation. This has allowed the field to move dramatically forward in studies of biliary regenerative medicine. In this review, the authors provide an overview of cholangiocytes, the organogenesis of the bile duct, cholangiopathies, and the current treatment and advances that have been made that are opening new doors to the study of cholangiopathies.
Bile Ducts
;
Bile
;
Bioprinting
;
Humans
;
Induced Pluripotent Stem Cells
;
Liver Transplantation
;
Mortality
;
Organogenesis
;
Rare Diseases
;
Regenerative Medicine
;
Tissue Donors
4.Applications of kidney organoids derived from human pluripotent stem cells.
Yong Kyun KIM ; Sun Ah NAM ; Chul Woo YANG
The Korean Journal of Internal Medicine 2018;33(4):649-659
The establishment of protocols to differentiate kidney organoids from human pluripotent stem cells provides potential applications of kidney organoids in regenerative medicine. Modeling of renal diseases, drug screening, nephrotoxicity testing of compounds, and regenerative therapy are attractive applications. Although much progress still remains to be made in the development of kidney organoids, recent advances in clustered regularly interspaced short palindromic repeat (CRISPR)-CRISPR-associated system 9 (Cas9) genome editing and three-dimensional bioprinting technologies have contributed to the application of kidney organoids in clinical fields. In this section, we review recent advances in the applications of kidney organoids to kidney disease modelling, drug screening, nephrotoxicity testing, and regenerative therapy.
Bioprinting
;
Clustered Regularly Interspaced Short Palindromic Repeats
;
Drug Evaluation, Preclinical
;
Genome
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Humans*
;
Kidney Diseases
;
Kidney*
;
Organoids*
;
Pluripotent Stem Cells*
;
Regenerative Medicine
;
Transplantation
5.Storage and use of cord blood
Journal of the Korean Medical Association 2018;61(9):557-565
Cord blood (CB) has been used as an important source for hematopoietic stem cell transplantation and has been stored in public CB banks (CBBs) worldwide since the mid-1990s. Recently, the application of cell-based therapy using CB has expanded its clinical utility for various refractory diseases and immunologic diseases through the manufacture of mesenchymal stem cells or induced pluripotent stem cells and the isolation of mononuclear cells from CB. In this review, I briefly summarize the biologic characteristics and banking process of CB, as well as the current status of public and private CBBs. I also review the current status of stem cell transplantation and cell-based therapy using CBs. Finally, I suggest strategies of banking CBs in anticipation of future medical advances.
Cell- and Tissue-Based Therapy
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Cryopreservation
;
Fetal Blood
;
Hematopoietic Stem Cell Transplantation
;
Immune System Diseases
;
Induced Pluripotent Stem Cells
;
Mesenchymal Stromal Cells
;
Population Characteristics
;
Stem Cell Transplantation
;
Transplantation
6.Generation of Induced Pluripotent Stem Cells and Neural Stem/Progenitor Cells from Newborns with Spina Bifida Aperta.
Yohei BAMBA ; Masahiro NONAKA ; Natsu SASAKI ; Tomoko SHOFUDA ; Daisuke KANEMATSU ; Hiroshi SUEMIZU ; Yuichiro HIGUCHI ; Ritsuko K POOH ; Yonehiro KANEMURA ; Hideyuki OKANO ; Mami YAMASAKI
Asian Spine Journal 2017;11(6):870-879
STUDY DESIGN: We established induced pluripotent stem cells (iPSCs) and neural stem/progenitor cells (NSPCs) from three newborns with spina bifida aperta (SBa) using clinically practical methods. PURPOSE: We aimed to develop stem cell lines derived from newborns with SBa for future therapeutic use. OVERVIEW OF LITERATURE: SBa is a common congenital spinal cord abnormality that causes defects in neurological and urological functions. Stem cell transplantation therapies are predicted to provide beneficial effects for patients with SBa. However, the availability of appropriate cell sources is inadequate for clinical use because of their limited accessibility and expandability, as well as ethical issues. METHODS: Fibroblast cultures were established from small fragments of skin obtained from newborns with SBa during SBa repair surgery. The cultured cells were transfected with episomal plasmid vectors encoding reprogramming factors necessary for generating iPSCs. These cells were then differentiated into NSPCs by chemical compound treatment, and NSPCs were expanded using neurosphere technology. RESULTS: We successfully generated iPSC lines from the neonatal dermal fibroblasts of three newborns with SBa. We confirmed that these lines exhibited the characteristics of human pluripotent stem cells. We successfully generated NSPCs from all SBa newborn-derived iPSCs with a combination of neural induction and neurosphere technology. CONCLUSIONS: We successfully generated iPSCs and iPSC-NSPCs from surgical samples obtained from newborns with SBa with the goal of future clinical use in patients with SBa.
Cells, Cultured
;
Ethics
;
Fibroblasts
;
Humans
;
Induced Pluripotent Stem Cells*
;
Infant, Newborn*
;
Meningomyelocele
;
Plasmids
;
Pluripotent Stem Cells
;
Regenerative Medicine
;
Skin
;
Spina Bifida Cystica*
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Spinal Cord
;
Spinal Dysraphism*
;
Stem Cell Transplantation
;
Stem Cells
7.Research progress of induced pluripotent stem cells in treatment of muscle atrophy.
Zhongkai YAO ; Chensong YANG ; Guixin SUN
Journal of Zhejiang University. Medical sciences 2016;45(2):147-151
Muscle atrophy caused by nerve injury is a common and difficult clinical problem. The development of stem cell researches has opened up a new way for the treatment of nerve injury-induced muscle atrophy. The induced pluripotent stem cells(iPSCs)can differentiate into various types of cells and have more advantages than embryonic stem cells (ESCs). After being transplanted into the damaged area, iPSCs are guided by neurogenic signals to the lesion sites, to repair the damaged nerve, promote generation of axon myelination, rebuild neural circuits and restore physiological function. Meanwhile, iPSCs can also differentiate into muscle cells and promote muscle tissue regeneration. Therefore, it would be possible to attenuate muscle atrophy caused by nerve injury with iPSCs treatment.
Animals
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Disease Models, Animal
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Embryonic Stem Cells
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Humans
;
Induced Pluripotent Stem Cells
;
cytology
;
transplantation
;
Muscular Atrophy
;
therapy
8.Generation and characterization of integration-free induced pluripotent stem cells from patients with autoimmune disease.
Mi Young SON ; Mi Ok LEE ; Hyejin JEON ; Binna SEOL ; Jung Hwa KIM ; Jae Suk CHANG ; Yee Sook CHO
Experimental & Molecular Medicine 2016;48(5):e232-
Autoimmune diseases (AIDs), a heterogeneous group of immune-mediated disorders, are a major and growing health problem. Although AIDs are currently treated primarily with anti-inflammatory and immunosuppressive drugs, the use of stem cell transplantation in patients with AIDs is becoming increasingly common. However, stem cell transplantation therapy has limitations, including a shortage of available stem cells and immune rejection of cells from nonautologous sources. Induced pluripotent stem cell (iPSC) technology, which allows the generation of patient-specific pluripotent stem cells, could offer an alternative source for clinical applications of stem cell therapies in AID patients. We used nonintegrating oriP/EBNA-1-based episomal vectors to reprogram dermal fibroblasts from patients with AIDs such as ankylosing spondylitis (AS), Sjögren's syndrome (SS) and systemic lupus erythematosus (SLE). The pluripotency and multilineage differentiation capacity of each patient-specific iPSC line was validated. The safety of these iPSCs for use in stem cell transplantation is indicated by the fact that all AID-specific iPSCs are integrated transgene free. Finally, all AID-specific iPSCs derived in this study could be differentiated into cells of hematopoietic and mesenchymal lineages in vitro as shown by flow cytometric analysis and induction of terminal differentiation potential. Our results demonstrate the successful generation of integration-free iPSCs from patients with AS, SS and SLE. These findings support the possibility of using iPSC technology in autologous and allogeneic cell replacement therapy for various AIDs, including AS, SS and SLE.
Autoimmune Diseases*
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Fibroblasts
;
Humans
;
In Vitro Techniques
;
Induced Pluripotent Stem Cells*
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Lupus Erythematosus, Systemic
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Pluripotent Stem Cells
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Spondylitis, Ankylosing
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Stem Cell Transplantation
;
Stem Cells
;
Transgenes
9.Evolution of Myelofibrosis Treatment.
Korean Journal of Medicine 2016;90(4):293-297
Myelofibrosis (MF) is a classical Philadelphia chromosome-negative myeloproliferative neoplasm characterized by clonal proliferation of pluripotent stem cells, dysfunctional kinase signaling, and abnormal cytokine release. MF is a heterogeneous disease, ranging from asymptomatic to being associated with one or more of the following problems: profound anemia, splenomegaly, constitutional issues, and even rapid progression to overt leukemia. Recently, important progress has been made. A Janus kinase (JAK) 2 mutation affects both pathogenesis and prognosis. Conventional treatment is primarily palliative and has only limited effects on the natural course of the disease. Allogeneic stem cell transplantation is the only curative treatment, but is presently limited to eligible intermediate-2 and high-risk patients. Ruxolitinib, the first drug approved by the Food and Drug Administration for treatment of intermediate-2 and high-risk patients, is currently the best available therapy for symptomatic MF patients. Additional JAK inhibitors are under investigation. Emerging therapies include immunomodulators and inhibitors of histone deacetylase (HDAC), mammalian target of rapamycin (mTOR), and telomerase. A better understanding of disease pathogenesis will lead to the development of better treatments modifying the disease course and, ultimately, curing the condition.
Anemia
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Histone Deacetylases
;
Humans
;
Immunologic Factors
;
Leukemia
;
Phosphotransferases
;
Pluripotent Stem Cells
;
Primary Myelofibrosis*
;
Prognosis
;
Sirolimus
;
Splenomegaly
;
Stem Cell Transplantation
;
Telomerase
;
United States Food and Drug Administration
10.Recent Stem Cell Advances: Cord Blood and Induced Pluripotent Stem Cell for Cardiac Regeneration- a Review.
Sheetal Kashinath MEDHEKAR ; Vikas Suresh SHENDE ; Anjali Baburao CHINCHOLKAR
International Journal of Stem Cells 2016;9(1):21-30
Stem cells are primitive self renewing undifferentiated cell that can be differentiated into various types of specialized cells like nerve cell, skin cells, muscle cells, intestinal tissue, and blood cells. Stem cells live in bone marrow where they divide to make new blood cells and produces peripheral stem cells in circulation. Under proper environment and in presence of signaling molecules stem cells begin to develop into specialized tissues and organs. These unique characteristics make them very promising entities for regeneration of damaged tissue. Day by day increase in incidence of heart diseases including left ventricular dysfunction, ischemic heart disease (IHD), congestive heart failure (CHF) are the major cause of morbidity and mortality. However infracted tissue cannot regenerate into healthy tissue. Heart transplantation is only the treatment for such patient. Due to limitation of availability of donor for organ transplantation, a focus is made for alternative and effective therapy to treat such condition. In this review we have discussed the new advances in stem cells such as use of cord stem cells and iPSC technology in cardiac repair. Future approach of CB cells was found to be used in tissue repair which is specifically observed for improvement of left ventricular function and myocardial infarction. Here we have also focused on how iPSC technology is used for regeneration of cardiomyocytes and intiating neovascularization in myocardial infarction and also for study of pathophysiology of various degenerative diseases and genetic disease in research field.
Blood Cells
;
Bone Marrow
;
Fetal Blood*
;
Heart Diseases
;
Heart Failure
;
Heart Transplantation
;
Humans
;
Incidence
;
Mortality
;
Muscle Cells
;
Myocardial Infarction
;
Myocardial Ischemia
;
Myocytes, Cardiac
;
Neurons
;
Organ Transplantation
;
Pluripotent Stem Cells*
;
Regeneration
;
Skin
;
Stem Cells*
;
Tissue Donors
;
Transplants
;
Ventricular Dysfunction, Left
;
Ventricular Function, Left

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