Stem Cell Reviews and Reports最新文献

Ischemic stroke is one of the leading causes of disability and mortality worldwide, posing a significant threat to human health. Neural stem cells possess the remarkable capabilities of self-renewal and differentiation into diverse neural cell types, endowing them with significant potential for the restoration of damaged neural tissues and functions. Exosomes, which carry a multitude of bioactive substances, serve as crucial tools for intercellular communication. Neural stem cell-derived exosomes are capable of engaging in the modulation of various physiological functions, presenting a highly promising novel approach for the treatment of ischemic stroke. This paper elaborates on the pathophysiological mechanisms of ischemic stroke, the engineering strategies for exosomes, and the prospects and limitations of neural stem cell transplantation therapies. It systematically reviews the potential roles of neural stem cell-derived exosomes in the treatment of ischemic stroke. Studies have shown that neural stem cell-derived exosomes can contribute to brain targeting, promote neural regeneration and angiogenesis, suppress neuroinflammation, and enhance the integrity of the blood-brain barrier in the treatment of ischemic stroke. However, their efficacy is constrained by insufficient targeting precision and limited cargo content. To improve the therapeutic efficacy of neural stem cell-derived exosomes, strategies such as surface modification and cargo loading can be employed. These include attaching targeting peptides, proteins, and antibodies to the exosome surface via chemical modification and genetic engineering, as well as loading small-molecule drugs and nanomaterials. Furthermore, accelerating the clinical translation of exosomes requires strict adherence to Good Manufacturing Practices. Neural stem cell-derived exosomes hold substantial potential in the treatment of ischemic stroke, which is expected to promote the development of the field of neural regeneration and bring new hope for more central nervous system diseases.

Mesenchymal stromal cells (MSCs) have gained significant attention in regenerative medicine for their potential in treating a variety of diseases even intractable ones, due to their ability to differentiate into various cell types and promote tissue repair. In addition to their regenerative properties, MSCs possess potent immunomodulatory effects, which make them particularly promising for treating orthopedic conditions and musculoskeletal disorders complicated by chronic inflammation, infection, or other comorbidities. This review explores the immunomodulatory mechanisms of MSCs and their role in facilitating bone and cartilage repair in conditions such as fractures, osteoarthritis, and tendon injuries. We examine the key mechanisms by which MSCs regulate the immune responses, including the paracrine activity by secreting cytokines, growth factors and extracellular vesicles on one hand, and modulation of immune cell activities through direct cell-cell contact. Furthermore, this review examines how comorbidities impact MSC function and quality and explores the potential of MSCs in treating orthopedic conditions complicated by diabetes, obesity, smoking, and infections, which can hinder the healing process. The challenges of translating MSC-based therapies into orthopaedic clinical practice are also discussed, particularly concerning MSC source selection, optimal dosing strategies and long-term safety and efficacy. Finally, we highlight emerging strategies aimed at enhancing the immunomodulatory effects of MSCs, such as preconditioning, genetic modifications, biomaterial-based delivery systems and combination therapies. A profound understanding of MSC immunomodulatory mechanisms can pave the way toward optimizing their application in orthopedic cell therapy and tissue engineering and enhancing clinical outcomes for patients with complex healing conditions.

Background: Mesenchymal stromal cells (MSCs) are currently employed in numerous clinical protocols, and have been used to enhance the regeneration of bone tissue in case of osteonecrosis, long bone and maxillary bone defects. Traditionally, these protocols were designed using freshly harvested, cultured MSCs. However, several limitations arose due to logistical issues, revealing the need to modify the protocol to facilitate the clinical process. In this context, cryopreservation and the use of the MSCs immediately after thawing seem to be the easiest way to overcome most of these constraints.

Methods: Bone marrow MSCs (BMSCs) of three donors were compared immediately after harvesting or thawing. First, the kinetics of cell viability and the gene expression profile were assessed in vitro. Then, the role of the cells in supporting vasculogenesis and bone formation in vivo was assessed using molecular biology and histology.

Results: Firstly, we observed a reduction in cell viability immediately after thawing, but no difference after 2 h. Furthermore, the gene expression profile was equivalent for genes involved in osteoblastic differentiation, vasculogenesis, inflammatory cytokines and proliferation. These in vitro results were confirmed by in vivo assays, which showed that cryopreservation did not affect their inflammatory response or vasculogenesis potential. Additionally, analysis of cell survival kinetics and bone formation assays revealed that cryo- and fresh-BMSCs exhibit equivalent potential to induce new bone formation and participate directly in bone formation, as evidenced by the expression of human osteoblastic genes.

Conclusion: Our study demonstrated that cryo-BMSCs possess the same properties as fresh BMSCs. Therefore, using cryo-BMSCs appears to be the optimal approach for future bone tissue engineering protocols and will facilitate the establishment of a BMSCs bank for future clinical trials.

Duchenne muscular dystrophy (DMD) is a severe X-linked disorder characterized by progressive muscle degeneration and premature mortality. This study evaluated the long-term safety and efficacy of DT-DEC01, a Dystrophin Expressing Chimeric (DEC) cell therapy, in non-ambulatory DMD patients following systemic intraosseous administration. Three non-ambulatory DMD patients aged 11 to 16 years, each carrying a different DMD mutation (deletion of exons 48-50, deletion of exon 52, or nonsense mutation), received DT-DEC01 at doses of 2 × 10⁶, 4 × 10⁶, and 6 × 10⁶ cells/kg, respectively, without immunosuppression. Safety assessment included monitoring of Adverse Events (AE), Serious Adverse Events (SAE), and Donor-Specific anti-HLA Antibodies (DSA). Efficacy evaluations included Performance of Upper Limb (PUL 2.0) test, grip strength, electromyography (EMG)-assessed Motor Unit Potential (MUP) duration, echocardiography, spirometry, and wristband-based arm movement quantification. No treatment-related AE, SAE, or DSA were detected through 24 months of follow-up. All three patients demonstrated measurable and sustained improvements across multiple functional domains following systemic DT-DEC01 administration. Patient-specific gains included improved cardiac parameters, prolonged MUP duration, enhanced respiratory capacity, and increased upper-limb strength. Notably, these improvements occurred in non-ambulatory patients - a disease stage typically associated with progressive cardiac and pulmonary decline, rather than functional recovery. These sustained functional benefits up to 24 months suggest that DT-DEC01 therapy may promote multisystem functional improvements in advanced DMD, independent of dystrophin mutation type or disease stage.

Chronic hyperglycemia in diabetes precipitates vascular damage and subsequent organ failure, yet the most critical defect is the inability to mount an adequate regenerative response. Numerous studies confirm that the reparative process, particularly angiogenesis, is profoundly defective in patients with diabetes. An increasingly vital area of investigation focuses on vasculogenesis: the de novo formation of blood vessels, involving specialized stem/progenitor cells. When these crucial repair cells and processes fail, complications in the target organ become inevitable and often irreversible. This review synthesizes our current understanding of how the complex diabetic milieu, marked by inflammation and metabolic stress, fundamentally corrupts the function, mobilization, and survival of these essential vascular regenerative populations. We highlight the known molecular mechanisms underlying this failure and, critically, examine emerging strategies to normalize these cellular abnormalities. Restoring robust vasculogenesis represents the next frontier in therapeutic development, holding the key to enhancing endogenous repair and successfully engineering new, functional vasculature to combat diabetic tissue damage.

Calcific aortic valve disease (CAVD) is a progressive and life-threatening condition characterized by fibrocalcific remodeling of the valve leaflets. Valvular interstitial cells (VICs) are central mediators of calcific aortic valve disease (CAVD), as their osteogenic trans-differentiation drives pathological matrix remodeling and calcium deposition within the valve leaflets. Human-induced pluripotent stem cell-derived valvular interstitial cells (hiVICs) represent a promising patient-specific platform for disease modeling. While primary VICs (pVICs) readily undergo mineralization under osteogenic stimulation, hiVICs fail to calcify in conventional two-dimensional (2D) cultures. Our data suggests that the inability of hiVICs to calcify in 2D culture is related to FOXO1 (Forkhead box protein O1) activity, which suppresses the osteogenic transcriptional program by inhibiting RUNX2 (Runt-related transcription factor 2). To address this limitation, we then developed a three-dimensional tissue ring construct using hiVICs. When cultured in osteogenic medium, these constructs exhibited robust calcification, as confirmed by Alizarin Red and Von Kossa staining. FOXO1 was also identified as a mediator of calcification in the tissue ring constructs. Metformin treatment restored FOXO1 expression and inhibited calcification, while AS1842856, a selective FOXO1 inhibitor, exacerbated tissue construct mineralization and led to a near-complete tissue collapse. In summary, we establish a functional 3D hiVIC-based model of CAVD enabling mechanistic investigation and pharmacological screening and identify FOXO1 as a critical regulator of osteogenic transition.

The skin is the body's most fundamental protective barrier but also a prominent indicator of aging. Skin aging is a complex process influenced by both intrinsic and extrinsic factors. In recent years, stem cell therapy has emerged as a novel approach widely applied in the field of skin rejuvenation. However, how Mesenchymal Stem Cells (MSCs) coordinately and dynamically regulate this network of pathways remains largely unknown. We propose an integrative hypothesis: MSCs improve skin rejuvenation through a dynamic, interactive multi-pathway network, exhibiting temporal and spatial specificity. We hypothesize that MSCs can dynamically regulate multiple signaling pathways at different levels, including MAPK, TGF-β/Smad, PI3K/Akt, Wnt/β-catenin, Notch, NF-κB, and Nrf2, to exert their therapeutic effects. By modulating the interactions between these pathways, including synergistic or antagonistic effects, and regulating various cellular responses such as anti-oxidation, anti-apoptosis, anti-inflammation, and promotion of dermal fibroblast proliferation, MSCs achieve skin rejuvenation. This knowledge may contribute to the future development of more precise targeted therapies and help in formulating tailored treatment strategies, potentially optimizing efficacy and mitigating the risk of subsequent complications.