Stem Cell Research & Therapy

BACKGROUND: Although oncogenic RAS mutants are thought to exert mutagenic effects upon blood cells, it remains uncertain how a single oncogenic RAS impacts non-transformed multipotent hematopoietic stem or progenitor cells (HPCs). Such potential pre-malignant status may characterize HPCs in patients with RAS-associated autoimmune lymphoproliferative syndrome-like disease (RALD). This study sought to elucidate the biological and molecular alterations in human HPCs carrying monoallelic mutant KRAS (G13C) with no other oncogene mutations...

BACKGROUND: Microglia, the brain's resident immune cells, play vital roles in brain development, and disorders like Alzheimer's disease (AD). Human iPSC-derived microglia (iMG) provide a promising model to study these processes. However, existing iMG generation protocols face challenges, such as prolonged differentiation time, lack of detailed characterization, and limited gene function investigation via CRISPR-Cas9. METHODS: Our integrated toolkit for in-vitro microglia functional genomics optimizes iPSC differentiation into iMG through a streamlined two-step, 20-day process, producing iMG with a normal karyotype...

BACKGROUND: Acute hypoxic proximal tubule (PT) injury and subsequent maladaptive repair present high mortality and increased risk of acute kidney injury (AKI) - chronic kidney disease (CKD) transition. Human bone marrow mesenchymal stem cell-derived exosomes (hBMMSC-Exos) as potential cell therapeutics can be translated into clinics if drawbacks on safety and efficacy are clarified. Here, we determined the real-time effective dose and treatment window of allogeneic hBMMSC-Exos, evaluated their performance on the structural and functional integrity of 3D microfluidic acute hypoxic PT injury platform...

BACKGROUND: Premature ovarian insufficiency (POI) is a major cause of infertility. In this study, we aimed to investigate the effects of the combination of bone marrow mesenchymal stem cells (BMSCs) and moxibustion (BMSCs-MOX) on POI and evaluate the underlying mechanisms. METHODS: A POI rat model was established by injecting different doses of cyclophosphamide (Cy). The modeling of POI and the effects of the treatments were assessed by evaluating estrous cycle, serum hormone levels, ovarian weight, ovarian index, and ovarian histopathological analysis...

In response to the growing demand for organ substitutes, tissue engineering has evolved significantly. However, it is still challenging to create functional tissues and organs. Tissue engineering from the 'bottom-up' is promising on solving this problem due to its ability to construct tissues with physiological complexity. The workflow of this strategy involves two key steps: the creation of building blocks, and the subsequent assembly. There are many techniques developed for the two pivotal steps. Notably, bioprinting is versatile among these techniques and has been widely used in research...

BACKGROUND: Oral ulcers are a common side effect of chemotherapy and affect patients' quality of life. While stem cell transplantation is a potential treatment for oral ulcers, its efficacy is limited as the stem cells tend to remain in the affected area for a short time. This study aims to develop a treatment for oral ulcers by using trimethyl chitosan (TMC) hydrogel with human tonsil-derived stem cells (hTMSCs) to increase the therapeutic effect of stem cells and investigate their effectiveness...

BACKGROUND: Erythroid and myeloid differentiation disorders are commonly occurred in leukemia. Given that the relationship between erythroid and myeloid lineages is still unclear. To find the co-regulators in erythroid and myeloid differentiation might help to find new target for therapy of myeloid leukemia. In hematopoiesis, ALA (alpha lipoic acid) is reported to inhibit neutrophil lineage determination by targeting transcription factor ELK1 in granulocyte-monocyte progenitors via splicing factor SF3B1...

BACKGROUND: Human induced pluripotent stem cell (iPSC)-derived peripheral sensory neurons present a valuable tool to model human diseases and are a source for applications in drug discovery and regenerative medicine. Clinically, peripheral sensory neuropathies can result in maladies ranging from a complete loss of pain to severe painful neuropathic disorders. Sensory neurons are located in the dorsal root ganglion and are comprised of functionally diverse neuronal types. Low efficiency, reproducibility concerns, variations arising due to genetic factors and time needed to generate functionally mature neuronal populations from iPSCs remain key challenges to study human nociception in vitro...

BACKGROUND: DNA damage and oxidative stress induced by chemotherapy are important factors in the onset of premature ovarian insufficiency (POI). Studies have shown that mitochondria derived from mesenchymal stem cells (MSC-Mito) are beneficial for age-related diseases, but their efficacy alone is limited. Pyrroloquinoline quinone (PQQ) is a potent antioxidant with significant antiaging and fertility enhancement effects. This study aimed to investigate the therapeutic effect of MSC-Mito in combination with PQQ on POI and the underlying mechanisms involved...

BACKGROUND: In vitro chondrogenesis of mesenchymal stromal cells (MSCs) driven by the essential chondro-inducer transforming growth factor (TGF)-β is instable and yields undesired hypertrophic cartilage predisposed to bone formation in vivo. TGF-β can non-canonically activate bone morphogenetic protein-associated ALK1/2/3 receptors. These have been accused of driving hypertrophic MSC misdifferentiation, but data remained conflicting. We here tested the antihypertrophic capacity of two highly specific ALK1/2/3 inhibitors - compound A (CompA) and LDN-212854 (LDN21) - in order to reveal potential prohypertrophic contributions of these BMP/non-canonical TGF-β receptors during MSC in vitro chondrogenesis...

BACKGROUND: Ovarian ageing is one of the major issues that impacts female fertility. Mesenchymal stem cell (MSC)-based therapy has made impressive progress in recent years. However, the efficacy and safety of MSCs, as nonautologous components, remain to be further verified. METHODS: Two common sources of MSCs, umbilical cord-derived MSCs (UC-MSCs) and adipose tissue-derived MSCs (AD-MSCs), were orthotopically transplanted into a mouse model of ovarian ageing to evaluate their therapeutic effects...

BACKGROUND: Human adipose stromal cells-derived extracellular vesicles (haMSC-EVs) have been shown to alleviate inflammation in acute lung injury (ALI) animal models. However, there are few systemic studies on clinical-grade haMSC-EVs. Our study aimed to investigate the manufacturing, quality control (QC) and preclinical safety of clinical-grade haMSC-EVs. METHODS: haMSC-EVs were isolated from the conditioned medium of human adipose MSCs incubated in 2D containers...

BACKGROUND: Spinal Muscular Atrophy (SMA) is an autosomal-recessive neuromuscular disease affecting children. It is caused by the mutation or deletion of the survival motor neuron 1 (SMN1) gene resulting in lower motor neuron (MN) degeneration followed by motor impairment, progressive skeletal muscle paralysis and respiratory failure. In addition to the already existing therapies, a possible combinatorial strategy could be represented by the use of adipose-derived mesenchymal stem cells (ASCs) that can be obtained easily and in large amounts from adipose tissue...

BACKGROUND: Spermatogonial stem cells (SSCs) were considered to be stem cells with limited potencies due to their existence in adult organisms. However, the production of spermatogonial stem cell colonies with broader differentiation capabilities in primary germ cell cultures from mice of select genetic backgrounds (C57BL6/Tg14, ddY, FVB and 129/Ola) indicated that SSCs from these strains were pluripotent. METHODS: We established primary cultures of SSCs from neonatal and adult Swiss 3T3 Albino mice...

Musculoskeletal disorders are the leading causes of physical disabilities worldwide. The poor self-repair capacity of musculoskeletal tissues and the absence of effective therapies have driven the development of novel bioengineering-based therapeutic approaches. Adipose-derived stem cell (ADSC)-based therapies are being explored as new regenerative strategies for the repair and regeneration of bone, cartilage, and tendon owing to the accessibility, multipotency, and active paracrine activity of ADSCs. In this review, recent advances in ADSCs and their optimization strategies, including ADSC-derived exosomes (ADSC-Exos), biomaterials, and genetic modifications, are summarized...

BACKGROUND: Previously, we have demonstrated that the batch variations of human platelet lysate (conventional MSC expansion medium) induce MSC heterogeneity and therapeutic inconsistency. On the other hand, the MSCs expanded with chemical defined medium have improved therapeutic consistency. METHODS: In the current study, we studied the MSC subpopulation composition and variation in different types and batches of MSC expansion medium with scRNA-seq analysis. RESULTS: MSCs expanded with different batches of media have higher levels of heterogeneity from the perspective of cell subpopulation composition at transcriptome levels and therapeutic inconsistency...

Premature ovarian insufficiency (POI) is an essential cause of reduced fertility and quality of life in young women. Mesenchymal stem cells (MSCs) and MSCs-derived extracellular vesicles (EVs) have the ability to migrate to damaged tissues and are considered as promising therapeutic approaches for POI. However, the homing ability and therapeutic efficacy of MSCs administered in vivo are still insufficient, and their potential tumorigenicity and multi-differentiation potential also bring many doubts about their safety...

BACKGROUND: Human pluripotent stem cells (hPSCs) have an enormous therapeutic potential, but large quantities of cells will need to be supplied by reliable, economically viable production processes. The suspension culture (three-dimensional; 3D) of hPSCs in stirred tank bioreactors (STBRs) has enormous potential for fuelling these cell demands. In this study, the efficient long-term matrix-free suspension culture of hPSC aggregates is shown. METHODS AND RESULTS: STBR-controlled, chemical aggregate dissociation and optimized passage duration of 3 or 4 days promotes exponential hPSC proliferation, process efficiency and upscaling by a seed train approach...

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BACKGROUND: The clinical application of human bone-marrow derived mesenchymal stem cells (MSCs) for the treatment of refractory diseases has achieved remarkable results. However, there is a need for a systematic evaluation of the quality and safety of MSCs sourced from donors. In this study, we sought to assess one potential factor that might impact quality, namely the age of the donor. METHODS: We downloaded two data sets from each of two Gene Expression Omnibus (GEO), GSE39035 and GSE97311 databases, namely samples form young (< 65 years of age) and old (> 65) donor groups...