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Induced pluripotent stem cells and their implication for regenerative medicine.

In 2006 Yamanaka's group showed that stem cells with properties similar to embryonic stem cells could be generated from mouse fibroblasts by introducing four genes. These cells were termed induced pluripotent stem cells (iPSCs). Because iPSCs avoid many of ethical concerns associated with the use of embryonic material, they have great potential in cell-based regenerative medicine. They are suitable also for other various purposes, including disease modelling, personalized cell therapy, drug or toxicity screening and basic research. Moreover, in the future, there might become possible to genera

Establishment of CD34 + hematopoietic stem cell-derived xenograft model of hyperleukocytic acute myeloid leukemia.

BACKGROUND: Hyperleukocytic acute myeloid leukemia (HLL) is marked by high early mortality and presents significant therapeutic challenges. Research on HLL is still in its infancy, and comprehensive development of patient-derived xenograft (PDX) models, especially CD34 + hematopoietic stem cell-derived models, remains limited. METHODS: We evaluated the establishment of the HLL model through blood examinations, smear analysis, bone marrow biopsy, flow cytometry, and mutation analysis. Correlation between survival times in mice and patients was assessed using linear regression. RESULTS: In the

Development and application of neural stem cells for treating various human neurological diseases in animal models.

Stem cells derived from adult tissues or the inner cell mass (ICM) of embryos in the mammalian blastocyst (BL) stage are capable of self-renewal and have remarkable potential for undergoing lineage-specific differentiation under in vitro culturing conditions. In particular, neural stem cells (NSCs) that self-renew and differentiate into major cell types of the brain exist in the developing and adult central nervous system (CNS). The exact function and distribution of NSCs has been assessed, and they represent an interesting population that includes astrocytes, oligodendrocytes, and neurons. Ma

Metabolism of Young and Aged Hematopoietic and Acute Myeloid Leukemia Stem Cells: Insights for Rejuvenation and Therapy.

Hematopoietic stem cells (HSCs) reside in the adult bone marrow and sustain the lifelong production of blood and immune cells. The processes of HSC quiescence, activation, and aging are complex and are orchestrated by a combination of intrinsic and extrinsic stimuli. Similarly, leukemic stem cells (LSCs) are responsible for the initiation of leukemia and drug resistance. Metabolic adaptations are critical for these processes, and research in this area is rapidly evolving. In this review, the metabolic programs, including glycolysis, mitochondrial metabolism, and amino acid and lipid metabolism

Novel therapeutic strategies for Asherman's syndrome: Endometrial regeneration using menstrual blood-derived stem cells.

Endometrium is vital to the establishment of pregnancy through its cyclical regeneration, which, when disrupted, can lead to endometrial thinning and Asherman's syndrome (AS). AS is characterized by infertility, pelvic pain, menstrual irregularities, and placental complications. Currently, treatments such as hysteroscopic adhesiolysis and hormone replacement therapy have demonstrated variable efficacy with limited clinical evidence. Recent developments in cell therapy have introduced menstrual blood-derived mesenchymal stem cells (MenSCs) as a promising alternative therapeutic strategy. Menstr

Oral Prednisolone, Apremilast and Human Umbilical Cord Mesenchymal Stem Cells in the Management of Pemphigus Foliaceus.

This case report showed a 60-year-old male with Pemphigus foliaceus (PF), complicated by hypertension, diabetes, and hepatitis B, for whom traditional treatments posed potential risks. The regimen included prednisone, human umbilical cord mesenchymal stem cells (UC-MSCs), and apremilast, showing several advancements: UC-MSCs addressed PF and comorbidities without reported side effects, accelerated steroid tapering substantially compared to apremilast monotherapy, and held superior benefits over hematopoietic stem cells. Over a 4-month follow-up, there was a marked improvement in the patient's

Vitiligo: An immune disease and its emerging mesenchymal stem cell therapy paradigm.

Melanocyte damage, innate immune response, adaptive immune response, and immune inflammatory microenvironment disorders are involved in the development of the immunological pathogenic mechanism of vitiligo. Mesenchymal stem cells are considered an ideal type of cells for the treatment of vitiligo owing to their low immunogenicity, lower rates of transplant rejection, and ability to secrete numerous growth factors, exosomes, and cytokines in vivo. The regulation of signaling pathways related to oxidative stress and immune imbalance in the immunological pathogenesis of vitiligo can improve the i

The first reported generation of human induced pluripotent stem cells (iPS cells) and iPS cell-derived cardiomyocytes in the Netherlands.

One of the recent breakthroughs in stem cell research has been the reprogramming of human somatic cells to an embryonic stem cell (ESC)-like state (induced pluripotent stem cells, iPS cells). Similar to ESCs, iPS cells can differentiate into derivatives of the three germ layers, for example cardiomyocytes, pancreatic cells or neurons. This technique offers a new approach to investigating disease pathogenesis and to the development of novel therapies. It may now be possible to generate iPS cells from somatic cells of patients who suffer from vascular genetic diseases, such as hereditary haemorr…

[Electrical stimulation promote proliferation and differentiation of endogenous neural stem cells in normal and injured spinal cord].

This article briefly reviews the general understanding of endogenous neural stem cells (eNSCs) in the CNS over the past 50 years. The proliferation and differentiation of neural progenitors continue throughout the lifetime, instead of cell division stopping at the postnatal period. In the spinal cord, these cells differentiate into different kinds of glial cells. Based on his current research in spinal cord injury (SCI), the author reports that the implantation of functional electrical stimulation (FES) in the motor cortex or the peripheral nerve increases cell birth and differentiation of eNS

Nuclear ataxias.

Historically basic neuroscience research has made several important contributions to the cell biology of the nucleus, in particular the elucidation of nuclear structures and compartments. As research progressed towards elucidating the mechanism of neurological disease at the cellular and molecular levels, it is now providing insight into the importance and basis of coordination of nuclear pathways within the nucleus and with other cellular compartments. Ataxias, lethal neurodegenerative diseases that are distinguished by a progressive loss of motor coordination, stem from disruption of nuclear

Triploid and diploid embryonic stem cell lines derived from tripronuclear human zygotes.

PURPOSE: Human embryonic stem cells (hESCs) are self-renewing, pluripotent cells that are valuable research tools and hold promise for use in regenerative medicine. The need for new hESC lines motivated our attempts to find a new resource for the derivation of hESC lines. The aim of this work was to establish more hESC lines from abnormal fertilized zygotes and to meet the emerging requirements for their use in cell replacement therapies, disease modeling, and basic research. METHODS: A total of 130 tripronuclear human zygotes was collected 18-20 h post-insemination and cultured in a modified

[Culture and application of thymic organoids: a review].

The thymus is a pivotal immune organ of the human body, and it is the place where T cells differentiate and mature. The damage of thymus would easily induce autoimmune diseases and even malignant tumors. For years, researchers have been exploring the process of T cell development and revealing the mechanism of thymic injury and regeneration generally through the monolayer culture system of T cells in vitro. However, the classic monolayer culture system could neither reproduce the unique three-dimensional epithelial reticular structure of the thymus, nor provide the cytokines and growth factors

Evaluation of the impact of customized serum-free culture medium on the production of clinical-grade human umbilical cord mesenchymal stem cells: insights for future clinical applications.

BACKGROUND: The selection of suitable culture medium is critical for achieving good clinical outcomes in cell therapy. To support the commercial application of stem cell therapy, customized culture media not only need to promote stem cell proliferation, but also need to save costs and meet industrial requirements for inter-batch consistency, efficacy, and biosafety. In this study, we developed a series of serum-free media (SFM) and elucidated the effects between different SFM, as well as between SFM and serum-containing meida (SCM), on human umbilical cord mesenchymal stem cells (hUC-MSCs) phe

Normal Numbers of Stem Cell Memory T Cells Despite Strongly Reduced Naive T Cells Support Intact Memory T Cell Compartment in Ataxia Telangiectasia.

Ataxia Telangiectasia (AT) is a rare inherited disorder characterized by progressive cerebellar ataxia, chromosomal instability, cancer susceptibility and immunodeficiency. AT is caused by mutations in the ATM gene, which is involved in multiple processes linked to DNA double strand break repair. Immunologically, ATM mutations lead to hampered V(D)J recombination and consequently reduced numbers of naive B and T cells. In addition, class switch recombination is disturbed resulting in antibody deficiency causing common, mostly sinopulmonary, bacterial infections. Yet, AT patients in general hav

3D bioprinting as a prospective therapeutic strategy for corneal limbal epithelial stem cell deficiency.

Limbal epithelial stem cells (LESCs) are responsible for the maintenance and repair of the corneal surface. Injuries and diseases of the eye may result in a vision condition called limbal stem cell deficiency (LSCD). Without limbal stem cells, the cornea becomes opaque, vascularized, and inflamed. Cultured LESC therapy as a treatment method was first described in 1997, and LESCs cultured from either patients or donors have been used to treat LSCD successfully. However, the main source of cornea for LSCD treatment is from donors, which are too few to meet the demand (less than 1:70 of cases). T

Anodal tDCS applied to the left frontal cortex abrogates scopolamine‑induced fear memory deficit via the dopaminergic system.

Plerixafor [Mozobil, AMD 3100, JM 3100, SDZ SID 791] is a bicyclam derivative that acts as a stem cell mobiliser by blocking the CXCR4 chemokine receptor. Plerixafor was synthesised by Johnson Matthey (AnorMED) in collaboration with the Rega Institute of Leuven, Belgium. Plerixafor is in phase III clinical trials in stem cell transplantation among cancer patients. Plerixafor blocks CXCR4, which triggers the rapid movement of stem cells out of the bone marrow and into circulating blood. These cells can then be collected and used in stem cell transplant procedures. Plerixafor had been available

Medical progress: Stem cells as a new therapeutic strategy for COVID-19.

Currently, the world is facing the SARS-CoV-2 pandemic, coronavirus of acute respiratory distress syndrome 2, causes of COVID-19. Coronaviruses are RNA single-stranded viruses that have an envelope. In addition, coronaviruses are classified into four subfamilies: alpha, beta, gamma and delta coronaviruses. The first of them, cause mildly symptomatic or asymptomatic infections, while beta-coronaviruses are responsible for severe diseases. SARS-CoV-2 belongs to the group of beta-coronaviruses. Current available therapies use corticosteroids to reduce inflammation, non-specific antiviral drugs or

Preclinical Efficacy of Peripheral Nerve Regeneration by Schwann Cell-like Cells Differentiated from Human Tonsil-Derived Mesenchymal Stem Cells in C22 Mice.

Charcot-Marie-Tooth disease (CMT) is a hereditary disease with heterogeneous phenotypes and genetic causes. CMT type 1A (CMT1A) is a type of disease affecting the peripheral nerves and is caused by the duplication of the peripheral myelin protein 22 (PMP22) gene. Human tonsil-derived mesenchymal stem cells (TMSCs) are useful for stem cell therapy in various diseases and can be differentiated into Schwann cell-like cells (TMSC-SCs). We investigated the potential of TMSC-SCs called neuronal regeneration-promoting cells (NRPCs) for peripheral nerve and muscle regeneration in C22 mice, a model for

Viral Vector-Based Innovative Approaches to Directly Abolishing Tumorigenic Pluripotent Stem Cells for Safer Regenerative Medicine.

Human pluripotent stem cells (hPSCs) are a promising source of regenerative material for clinical applications. However, hPSC transplant therapies pose the risk of teratoma formation and malignant transformation of undifferentiated remnants. These problems underscore the importance of developing technologies that completely prevent tumorigenesis to ensure safe clinical application. Research to date has contributed to establishing safe hPSC lines, improving the efficiency of differentiation induction, and indirectly ensuring the safety of products. Despite such efforts, guaranteeing the clinica

Tissue-Resident Myeloid and Histiocytic Cells in Health and Disease: Novel Emerging Concepts.

Although all myeloid cells are considered to derive from hematopoietic stem cells, the cells in each myeloid lineage are heterogeneous populations, and their distribution and functions vary, depending on underlying physiologic and pathologic processes, age, sex, and genetic and epigenetic signatures. In general, myeloid cells can be separated into circulating and tissue-resident cells. Tissue-resident myeloid cells can further be divided into cells derived from circulating monocytes, circulating stem cells, or local tissue-restricted stem or progenitor cells. Depending on underlying diseases a

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… Sovalat H., Racadot E., Ojeda M., et al., “CD34+ Cells and CD34+CD38‐ Subset From Mobilized Blood Show Different Patterns of Adhesion Molecules Compared to Those From Steady‐State Blood, Bone Marrow, and Cord Blood,” Journal of Hematotherapy & Stem Cell Research 12, no. 5 (2003): 473–489. 37. …