Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-04964-z
Background Psoriasis is a refractory immune-related disease. In recent years, it has been discovered that mesenchymal stem cells (MSCs) can be used as a new therapeutic approach for psoriasis, but their potential therapeutic mechanism remains unclear. This study aims to explore the role of MSCs in the treatment of psoriasis. Methods We employed a mouse psoriasis model induced by imiquimod (IMQ) in vivo and a co-culture system of MSCs and HaCaT keratinocytes (KCs) cell line in vitro. These approaches allowed us to investigate the effect of MSCs on the levels of inflammatory factors and the activation of inflammasomes in both contexts. Mouse-targeted amino acid sequencing, transmission electron microscopy for in vitro observation, immunofluorescence for both in vivo and in vitro analyses, and siRNA transfection in vitro were employed in this study. Results Our results showed that MSCs significantly improved the skin lesion of mice with psoriasis, and reduced the levels of inflammatory factors and chemokines including IL-1β, IL-6, IL-8, TNF-α, MCP-1, CCL7, CCL20 and CCL27 in the mouse skin lesion areas and M5- induced psoriatic KCs models in vitro. Likewise, MSCs repaired the skin barrier by enhancing claudin-1 expression in vivo. In addition, MSCs increased KRT1 and decreased KRT6 levels in vivo and in vitro. Amino acid metabolism analysis showed that MSCs could improve the serine metabolism level in the mouse skins and upregulated the key enzyme phosphoserine phosphatase (PSPH) in serine metabolism. In vitro experiments demonstrated that knockdown of PSPH could reverse the therapeutic effects of MSCs on psoriasis. Furthermore, studies in vitro and in vivo revealed that MSCs can activate the PINK1-Parkin pathway. It was specifically manifested by elevated levels of PINK1, Parkin, p-Parkin, Beclin-1, and LC3B-II/I, coupled with a reduction in P62 protein. Subsequently, the activation of PINK1-Parkin led to decreased expressions of IL-1β, IL-6, IL-8, TNF-α, CCL7, CCL20, CCL27, and MCP-1. In vitro and in vivo experiments indicated that MSCs can reduce the levels of IL-1β, IL-6, IL-8, TNF-α, CCL7, CCL20, CCL27, and MCP-1 by inhibiting the activation of NLRP3 inflammasomes. Meanwhile, PSPH knockdown in vitro can reverse the activating effects of MSCs on the PINK1-Parkin, as shown by decreased levels of PINK, Parkin, p-Parkin, Beclin-1, and LC3B-II/I, concurrently with an elevation in P62. Conclusions The results of this study indicated that MSCs can alleviate IMQ-induced psoriasiform dermatitis in mice by upregulating serine metabolism. The key serine metabolism enzyme PSPH may enhance PINK1/Parkin-mediated mitochondrial autophagy in psoriatic HaCaT and inhibit NLRP3 inflammasome activation in HaCaT cells, thereby alleviating skin inflammatory responses and suppressing skin proliferation in psoriatic mice.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-04964-z
Psoriasis is a chronic inflammatory skin disease affecting 2-3% of the global population. Mesenchymal stem cells (MSCs) have emerged as a potential therapy, but the underlying mechanisms remain unclear. This study investigated the therapeutic effects of adipose-derived MSCs on imiquimod (IMQ)-induced psoriasis in mice and M5-induced psoriatic HaCaT keratinocytes in vitro. MSCs significantly ameliorated skin lesions, reduced inflammatory cytokines (IL-1β, IL-6, IL-8, TNF-α) and chemokines (MCP-1, CCL7, CCL20, CCL27), and restored skin barrier function by upregulating claudin-1. MSCs also normalized keratinocyte differentiation markers (increased KRT1, decreased KRT6). Amino acid metabolomics revealed that MSCs enhanced serine metabolism in mouse skin, upregulating phosphoserine phosphatase (PSPH). Knockdown of PSPH reversed the therapeutic effects of MSCs in vitro. Mechanistically, MSCs activated the PINK1-Parkin mitophagy pathway, as evidenced by increased PINK1, Parkin, p-Parkin, Beclin-1, and LC3B-II/I ratios, and decreased P62. This activation attenuated NLRP3 inflammasome activation and restrained keratinocyte hyperproliferation. The study concludes that MSCs alleviate psoriasis via PSPH-mediated activation of PINK1-Parkin mitophagy, suppressing NLRP3 inflammasome. Limitations include the need to identify specific MSC-secreted factors and lack of clinical validation. These findings provide a rationale for developing PSPH-targeted therapies for psoriasis.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-04964-z
Background: Psoriasis is a refractory immune-related disease. In recent years, it has been discovered that mesenchymal stem cells (MSCs) can be used as a new therapeutic approach for psoriasis, but their potential therapeutic mechanism remains unclear. This study aims to explore the role of MSCs in the treatment of psoriasis. Methods: We employed a mouse psoriasis model induced by imiquimod (IMQ) in vivo and a co-culture system of MSCs and HaCaT keratinocytes (KCs) cell line in vitro. These approaches allowed us to investigate the effect of MSCs on the levels of inflammatory factors and the activation of inflammasomes in both contexts. Mouse-targeted amino acid sequencing, transmission electron microscopy for in vitro observation, immunofluorescence for both in vivo and in vitro analyses, and siRNA transfection in vitro were employed in this study. Results: Our results showed that MSCs significantly improved the skin lesion of mice with psoriasis, and reduced the levels of inflammatory factors and chemokines including IL-1β, IL-6, IL-8, TNF-α, MCP-1, CCL7, CCL20 and CCL27 in the mouse skin lesion areas and M5-induced psoriatic KCs models in vitro. Likewise, MSCs repaired the skin barrier by enhancing claudin-1 expression in vivo. In addition, MSCs increased KRT1 and decreased KRT6 levels in vivo and in vitro. Amino acid metabolism analysis showed that MSCs could improve the serine metabolism level in the mouse skins and upregulated the key enzyme phosphoserine phosphatase (PSPH) in serine metabolism. In vitro experiments demonstrated that knockdown of PSPH could reverse the therapeutic effects of MSCs on psoriasis. Furthermore, studies in vitro and in vivo revealed that MSCs can activate the PINK1-Parkin pathway. It was specifically manifested by elevated levels of PINK1, Parkin, p-Parkin, Beclin-1, and LC3B-II/I, coupled with a reduction in P62 protein. Subsequently, the activation of PINK1-Parkin led to decreased expressions of IL-1β, IL-6, IL-8, TNF-α, CCL7, CCL20, CCL27, and MCP-1. In vitro and in vivo experiments indicated that MSCs can reduce the levels of these inflammatory factors by inhibiting the activation of NLRP3 inflammasomes. Meanwhile, PSPH knockdown in vitro can reverse the activating effects of MSCs on the PINK1-Parkin, as shown by decreased levels of PINK, Parkin, p-Parkin, Beclin-1, and LC3B-II/I, concurrently with an elevation in P62. Conclusions: The results of this study indicated that MSCs can alleviate IMQ-induced psoriasiform dermatitis in mice by upregulating serine metabolism. The key serine metabolism enzyme PSPH may enhance PINK1/Parkin-mediated mitochondrial autophagy in psoriatic HaCaT and inhibit NLRP3 inflammasome activation in HaCaT cells, thereby alleviating skin inflammatory responses and suppressing skin proliferation in psoriatic mice.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21267
BACKGROUND: Sarcopenia and osteoporosis have attracted significant attention in the academic community due to their high prevalence and severe adverse outcomes. Although existing studies have suggested a potential causal relationship between sarcopenia and osteoporosis, the evidence remains insufficient. OBJECTIVE: Based on large-scale genome-wide data, to explore the causal relationship between genetically predicted sarcopenia and osteoporosis through a bidirectional Mendelian randomization approach. METHODS: Genome-wide significant loci (P < 5×10-8) associated with sarcopenia-related traits were selected from the UK Biobank database (an open database jointly developed by the UK government, the Medical Research Council, and the Wellcome Trust), followed by linkage disequilibrium analysis. Osteoporosis data were obtained from the GEnetic Factors for OSteoporosis Consortium (GEFOS; an open database funded by the EU Framework Program for Research and Development, jointly led by Erasmus University Medical Center in the Netherlands), including 28,498 European ancestry subjects, with a focus on data from osteoporosis-prone fracture sites. The study used inverse variance weighting as the primary analysis method, supplemented by MR-Egger regression, weighted median method, and MR-RAPS for multiple validation. To ensure the reliability of the results, multiple sensitivity analyses were performed. RESULTS AND CONCLUSION: Inverse variance weighting analysis showed a bidirectional causal relationship between whole-body fat-free mass and bone mineral density (P < 0.05). Forward causal analysis indicated that whole-body fat-free mass was positively associated with lumbar spine bone mineral density (OR=1.124, 95%CI: 1.008-1.253, P=0.035) and negatively associated with forearm bone mineral density (OR=0.821, 95%CI: 0.699-0.966, P=0.017). Reverse causal analysis showed that forearm bone mineral density (OR=1.033, 95%CI: 1.002-1.066, P=0.036), lumbar spine bone mineral density (OR=1.054, 95%CI: 1.025-1.084, P < 0.001), and femoral neck bone mineral density (OR=1.059, 95%CI: 1.008-1.113, P=0.021) were all positively associated with whole-body fat-free mass. A reduction in whole-body fat-free mass can lead to decreased lumbar spine bone mineral density, and a decrease in bone mineral density at various sites further exacerbates the loss of whole-body fat-free mass. Although the data in this study mainly come from European populations, due to the universality of genome-wide association analysis methods and the commonality of genetic backgrounds, the results still have important reference value for exploring the pathogenesis of sarcopenia and osteoporosis in the Chinese population, formulating clinical intervention strategies, and assessing genetic risk.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21355
BACKGROUND: In recent years, multiple epidemiological studies have suggested a potential pathological link between sarcopenia and cognitive impairment. However, due to methodological limitations in traditional observational studies and difficulties in controlling confounding factors, their genetic-level causal relationship has not yet been fully elucidated. OBJECTIVE: To systematically analyze the causal relationship and underlying pathogenesis between sarcopenia and cognitive impairment in European populations using Mendelian randomization methods. METHODS: This study utilized genome-wide association study (GWAS) summary data for sarcopenia-related phenotypes (whole-body fat-free mass, hand grip strength, and walking speed) from the UK Biobank, and cognitive function GWAS summary data from the IEU database. After rigorous threshold filtering and linkage disequilibrium clumping, bidirectional Mendelian randomization analyses were performed. Forward analysis used sarcopenia-related traits as exposures and cognitive function as the outcome; reverse analysis swapped the direction. Inverse variance weighting was the primary analysis method, supplemented by weighted median, MR-Egger regression, and robust adjusted profile scoring. Heterogeneity and sensitivity analyses were conducted to ensure robustness. RESULTS AND CONCLUSION: Forward MR-IVW analysis showed that whole-body fat-free mass (OR=1.091, 95%CI: 1.001-1.188, P=0.045), left hand grip strength (OR=1.283, 95%CI: 1.077-1.527, P=0.005), right hand grip strength (OR=1.220, 95%CI: 1.022-1.456, P=0.027), and walking speed (OR=3.069, 95%CI: 1.997-4.717, P<0.001) were significantly positively associated with cognitive function. Reverse analysis showed that cognitive function had a significant positive causal effect only on walking speed (OR=1.023, 95%CI: 1.004-1.043, P=0.014), but not on fat-free mass or grip strength. Sensitivity analyses indicated some heterogeneity but no horizontal pleiotropy. The findings suggest a causal relationship between sarcopenia and cognitive impairment, indicating that sarcopenia may serve as a predictor for cognitive impairment, providing a theoretical basis for early clinical screening. This study, based on international public databases, offers new evidence for the association between sarcopenia and cognitive impairment in Chinese populations and has important reference value for early screening and prevention of both diseases.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21058
BACKGROUND: Hemiplegia, a prevalent stroke-related condition, is often studied for motor dysfunction; however, spasticity remains under-researched. Abnormal muscle tone significantly hinders hemiplegic patients' walking recovery. OBJECTIVE: To determine whether early suspension-protected training with a personal assistant machine for stroke patients enhances walking ability and prevents muscle spasms. METHODS: Thirty-two early-stage stroke patients from Shenzhen University General Hospital and the China Rehabilitation Research Center were randomly assigned to the experimental group (n=16) and the control group (n=16). Both groups underwent 4 weeks of gait training under the suspension protection system for 30 minutes daily, 5 days a week. The experimental group used the personal assistant machine during training. Three-dimensional gait analysis (using the Cortex motion capture system), Brunnstrom staging, Fugl-Meyer Assessment for lower limb motor function, Fugl-Meyer balance function, and the modified Ashworth Scale were evaluated within 1 week before the intervention and after 4 weeks of intervention. RESULTS AND CONCLUSION: After the 4-week intervention, all outcome measures showed significant changes in each group. The experimental group had a small but significant increase in the modified Ashworth Scale score (P < 0.05, d=|0.15|), while the control group had a large significant increase (P < 0.05, d=|1.48|). The experimental group demonstrated greater improvements in walking speed (16.5 to 38.44 cm/s, P < 0.05, d=|4.01|), step frequency (46.44 to 64.94 steps/min, P < 0.05, d=|2.32|), stride length (15.50 to 29.81 cm, P < 0.05, d=|3.44|), and peak hip and knee flexion (d=|1.82| to |2.17|). After treatment, the experimental group showed significantly greater improvements than the control group in walking speed (38.44 vs. 26.63 cm/s, P < 0.05, d=|2.75|), stride length, peak hip and knee flexion (d=|1.31| to |1.45|), step frequency (64.94 vs. 59.38 steps/min, P < 0.05, d=|0.85|), and a reduced support phase (bilateral: 24.31% vs. 28.38%, P < 0.05, d=|0.88|; non-paretic: 66.19% vs. 70.13%, P < 0.05, d=|0.94|). For early hemiplegia, personal assistant machine-assisted gait training under the suspension protection system helps establish a correct gait pattern, prevents muscle spasms, and improves motor function.