Adult Germline Stem Cells ; Humans ; Male ; Mutation ; Spermatogenesis ; Spermatogonia

Continuous spermatogenesis depends on the self-renewal and differentiation of spermatogonial stem cells (SSCs). SSCs, the only male reproductive stem cells that transmit genetic material to subsequent generations, possess an inherent self-renewal ability, which allows the maintenance of a steady stem cell pool. SSCs eventually differentiate to produce sperm. However, in an in vitro culture system, SSCs can be induced to differentiate into various types of germ cells. Rodent SSCs are well defined, and a culture system has been successfully established for them. In contrast, available information on the biomolecular markers and a culture system for livestock SSCs is limited. This review summarizes the existing knowledge and research progress regarding mammalian SSCs to determine the mammalian spermatogenic process, the biology and niche of SSCs, the isolation and culture systems of SSCs, and the biomolecular markers and identification of SSCs. This information can be used for the effective utilization of SSCs in reproductive technologies for large livestock animals, enhancement of human male fertility, reproductive medicine, and protection of endangered species.
Adult Germline Stem Cells ; Animals ; Cell Differentiation ; Male ; Spermatogenesis ; Spermatogonia ; Stem Cells

Azoospermia patients who carry a monogenetic mutation that causes meiotic arrest may have their biological child through genetic correction in spermatogonial stem cells (SSCs). However, such therapy for infertility has not been experimentally investigated yet. In this study, a mouse model with an X-linked testis-expressed 11 (TEX11) mutation (Tex11
Adult Germline Stem Cells/metabolism* ; Animals ; Azoospermia/genetics* ; Infertility, Male/therapy* ; Male ; Mice ; Mutation/genetics* ; Spermatogenesis/genetics*

While it is known that spermatogonial stem cells (SSCs) initiate the production of male germ cells, the mechanisms of SSC self-renewal, proliferation, and differentiation remain poorly understood. We have previously identified Strawberry Notch 1 (SBNO1), a vertebrate strawberry notch family protein, in the proteome profile for mouse SSC maturation and differentiation, revealing SBNO1 is associated with neonatal testicular development. To explore further the location and function of SBNO1 in the testes, we performed Sbno1 gene knockdown in mice to study the effects of SBNO1 on neonatal testicular and SSC development. Our results revealed that SBNO1 is required for neonatal testicular and SSC development in mice. Particularly, in vitro Sbno1 gene knockdown with morpholino oligonucleotides caused a reduction of SSCs and inactivation of the noncanonical Wnt pathway, through Jun N-terminal kinases. Our study suggests SBNO1 maintains SSCs by promoting the noncanonical Wnt pathway.
Adult Germline Stem Cells/metabolism* ; Animals ; Cell Proliferation/physiology* ; Gene Knockdown Techniques ; Male ; Mice ; Proteome ; Repressor Proteins/metabolism* ; Testis/metabolism* ; Wnt Signaling Pathway/physiology*

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'.
Adult Stem Cells ; Hematopoietic Stem Cells ; Human Rights ; Humans ; Induced Pluripotent Stem Cells ; Medical Tourism ; Mesenchymal Stromal Cells ; Stem Cells

An ideal animal model of azoospermia would be a powerful tool for the evaluation of spermatogonial stem cell (SSC) transplantation. Busulfan has been commonly used to develop such a model, but 30%-87% of mice die when administered an intraperitoneal injection of 40 mg kg^-1. In the present study, hematoxylin and eosin staining, Western blot, immunofluorescence, and quantitative real-time polymerase chain reaction were used to test the effects of busulfan exposure in a mouse model that received two intraperitoneal injections of busulfan at a 3-h interval at different doses (20, 30, and 40 mg kg^-1) on day 36 or a dose of 40 mg kg^-1 at different time points (0, 9, 18, 27, 36, and 63 days). The survival rate of the mice was 100%. When the mice were treated with 40 mg kg^-1 busulfan, dramatic SSC depletion occurred 18 days later and all of the germ cells were cleared by day 36. In addition, the gene expressions of glial cell line-derived neurotrophic factor (GDNF), fibroblast growth factor 2 (FGF2), chemokine (C-X-C Motif) ligand 12 (CXCL12), and colony-stimulating factor 1 (CSF1) were moderately increased by day 36. A 63-day, long-term observation showed the rare restoration of endogenous germ cells in the testes, suggesting that the potential period for SSC transplantation was between day 36 and day 63. Our results demonstrate that the administration of two intraperitoneal injections of busulfan (40 mg kg^-1 in total) at a 3-h interval to mice provided a nonlethal and efficient method for recipient preparation in SSC transplantation and could improve treatments for infertility and the understanding of chemotherapy-induced gonadotoxicity.
Adult Germline Stem Cells/transplantation* ; Animals ; Azoospermia/chemically induced* ; Busulfan/toxicity* ; Disease Models, Animal ; Infertility, Male/chemically induced* ; Injections, Intraperitoneal ; Male ; Mice ; Spermatogenesis/drug effects* ; Spermatogonia/drug effects* ; Stem Cell Transplantation/methods*

Stem cells are undifferentiated cells capable of generating, sustaining, and replacing terminally differentiated cells and tissues. They can be isolated from embryonic as well as almost all adult tissues including skin, but are also generated through genetic reprogramming of differentiated cells. Preclinical and clinical research has recently tremendously improved stem cell therapy, being a promising treatment option for various diseases in which current medical therapies fail to cure, prevent progression or relieve symptoms. With the main goal of regeneration or sustained genetic correction of damaged tissue, advanced tissue-engineering techniques are especially applicable for many dermatological diseases including wound healing, genodermatoses (like the severe blistering disorder epidermolysis bullosa) and chronic (auto-)inflammatory diseases. This review summarizes general aspects as well as current and future perspectives of stem cell therapy in dermatology.
Adult ; Blister ; Dermatology* ; Epidermolysis Bullosa ; Humans ; Induced Pluripotent Stem Cells ; Regeneration ; Skin ; Stem Cells* ; Wound Healing

Osteoarthritis is a musculoskeletal disease representative of an aging society. As medical conditions are usually complicated in an aging population, osteoarthritis becomes more frequently encountered in the physician's office. There is a growing need, therefore, for physicians to pay attention to this common orthopedic condition. Cartilage degeneration, arthritic pain, and joint dysfunction are major manifestations of osteoarthritis, and degenerated cartilage is difficult to repair with conventional treatment modalities. Scientists and physicians have developed various therapeutic strategies, including the use of stem cells. Here, we discuss previous and current progress in cartilage regenerative therapy against osteoarthritis.
Adult Stem Cells ; Aging ; Cartilage ; Chondrogenesis ; Induced Pluripotent Stem Cells ; Joints ; Musculoskeletal Diseases ; Orthopedics ; Osteoarthritis ; Physicians' Offices ; Stem Cells

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

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.
Adult ; Adult Stem Cells ; Biomarkers ; Cell Lineage ; Developmental Biology ; Drug Evaluation, Preclinical ; Embryonic Stem Cells ; Fibroblasts ; Financial Management ; Humans ; Induced Pluripotent Stem Cells ; Mass Screening ; Pluripotent Stem Cells ; Regenerative Medicine ; Stem Cell Research ; Stem Cells