Adipose tissue secretome plays a crucial role in the mechanisms of metabolic diseases. Weight loss has a favourable effect on the adipose tissue secretome and prevents the development of type 2 diabetes mellitus (T2DM) and its complications. The most effective methods of glycaemic control are bariatric surgery (BS) and pharmacotherapy. The aim of our study is to evaluate changes in adipose tissue secretome after BS and semaglutide injections.
17 patients with T2DM were examined before and 6 months after BS or semaglutide therapy. The examination protocol included anthropometry, clinical biochemistry, insulin resistance evaluation and collection of subcutaneous adipose tissue biopsies. Adipose derived stem cells (ADSC) were isolated from biopsies according to a standard enzymatic protocol and differentiated into white and beige adipocytes. Adipogenesis and thermogenesis were assessed by confocal microscopy. Secretome of adipocytes and cytokines plasma levels were analyzed using a MILLIPLEX panel.
Following BS and semaglutide therapy, a decline in BMI, total fat content, HbA1c, and fasting blood glucose was observed. Insulin sensitivity increased only 6 months after BS. Semaglutide therapy resulted in the elevation of angiogenic and proinflammatory cytokines in adipocyte secretory profile. After BS we also detected the increase in proinflammatory cytokines both in adipocyte secretome and in plasma levels. However, the adipocyte secretome subsequent to bariatric surgery (BS) exhibited a reduced proinflammatory response in comparison to that observed following semaglutide therapy.
The effect of semaglutide injections directly on adipose tissue can change the function of ADSC, making them more angiogenic and adipogenic. A decrease in BMI, HbA1c and insulin resistance is achieved to a significant extent only after BS. BS-induced T2DM remission is related to lower pro-inflammatory secretion from adipocytes as compared to semaglutide. The regulation of inflammation in adipocytes may serve as a potential mechanism underlying BS-induced T2DM remission.
© 2025. The Author(s).

Cancer-associated mesenchymal stem cells (Ca-MSCs), an integral part of the tumor microenvironment, play a major role in modulating tumor progression; they have been reported to progress as well as inhibit various cancers, including cervical cancer. To understand the exact role of Ca-MSCs in tumor modulation, it is necessary to have an optimized protocol for Ca-MSCs isolation. This work demonstrates the isolation and expansion of a primary culture of cervical cancer-associated MSCs (CCa-MSCs) from the biopsy sample of cervical cancer patients using the explant culture technique. The isolated cells were characterized according to International Society for Cellular Therapy (ISCT) guidelines. Morphological analysis revealed that cells were adherent to the plastic surface and possessed spindle-shaped morphology. Flow cytometry analysis of the cells showed high expression (~98%) for MSC-specific cell surface markers (CD90, CD73, and CD105), negative expression (<0.5%) for endothelial cell marker (CD34) and hematopoietic cell marker (CD45), and negligible expression for HLA-DR, as recommended by ISCT. Further, trilineage differentiation potential analysis of the cells showed their osteogenic and chondrogenic potential and adipogenic differentiation. This standardized protocol will assist in the cultivation of CCa-MSCs and the study of their interactions with tumor cells and other components of the tumor microenvironment. This protocol may be utilized in the establishment of Ca-MSCs from other types of cancers as well. Key features • Isolation and expansion of cervical cancer-associated mesenchymal stem cells (CCa-MSCs) from patient biopsy sample. • Characterization of isolated CCa-MSCs for the presence of MSC-specific cell surface markers and trilineage differentiation potential. • CCa-MSCs can be employed to study the interactions with the tumor cells in the tumor microenvironment. Graphical overview.
©Copyright : © 2025 The Authors; This is an open access article under the CC BY-NC license.

Intervertebral disc degeneration (IDD) is characterized by oxidative-stress driven progressive apoptosis and senescence of nucleus pulposus mesenchymal stem cells (NP-MSCs). MOTS-c, a 16-amino acid peptide encoded by the mitochondrial 12S rRNA open reading frame, has emerged as a key regulator of cellular metabolism, oxidative stress, and senescence. This study investigated the therapeutic potential of MOTS-c in countering tert-butyl hydroperoxide (TBHP)-induced oxidative damage in NP-MSCs, and we developed a novel biomaterial strategy for IDD treatment.Key findings include.
MOTS-c significantly attenuated TBHP-induced NP-MSC apoptosis (Annexin V+/PI + cells reduced by 48 %, p < 0.001), senescence (SA-β-gal + cells decreased by 52 %, p < 0.005), and ROS overproduction (35 % reduction, p < 0.0001) via activation of the AMPK/SIRT1 pathway. Pharmacological inhibition of SIRT1 abolished these protective effects, confirming pathway specificity.
A sustained-release MOTS-c delivery system (RAD/RMOTS-c) was engineered by conjugating MOTS-c to the self-assembling RADA16-I peptide. The hydrogel exhibited a β-sheet-rich nanofibrous structure (fiber diameter: 362.6 nm), shear-thinning rheology (viscosity: 131-217 Pa s), and sustained peptide release over 7 days.
RAD/RMOTS-c enhanced NP-MSC viability (1.8-fold vs. control, p < 0.005) and extracellular matrix (ECM) synthesis, elevating collagen II/aggrecan expression (2.3-fold, p < 0.05) while suppressing collagen I (63 % reduction, p < 0.001).In Vivo Therapeutic Validation: In a rat IDD model, RAD/RMOTS-c injection preserved disc height (DHI%: 82.4 vs. 58.7 in IDD group, p < 0.001), restored T2-weighted MRI signals (1.5-fold increase, p < 0.001), and reduced histological degeneration scores by 44 % compared to untreated controls (p < 0.001).
This work (1) demonstrates the association between MOTS-c's anti-degenerative effects and AMPK/SIRT1 signaling in NP-MSCs and (2) pioneers a peptide-hydrogel hybrid system that synergistically combines mitochondrial protection with structural support for disc regeneration. The findings can advance IDD therapy toward biology-driven, minimally invasive solutions, aligning with the paradigm of functional biomaterials for degenerative diseases.
© 2025 The Authors.

Human menstrual blood-derived stem cells (MenSCs), a major class of mesenchymal stem cells (MSCs), modulate intercellular signals via paracrine factors. Previous studies found that MenSC-derived secretomes exert protective effects against liver fibrosis. However, the underlying mechanisms of these observations remain unclear.
Extracellular Matrix Protein 1 (ECM1), identified in MenSCs culture medium using mass spectrometry, was employed to stably overexpress ECM1-HA or silence in MenSCs using lentiviral vectors. These genetically engineered cells were either intravenously injected into the carbon tetrachloride (CCl4)-induced liver fibrosis mice or co-cultured with hepatic stellate cells (HSCs)-LX-2. The interaction between ECM1 and low-density lipoprotein receptor-related protein 1α (LRP1α) was confirmed using Co-Immunoprecipitation (Co-ip), Duolink Proximity Ligation Assays (PLA) and pull-down. LRP1 deficient mice were generated via intravenous administration of adeno-associated-virus-8. The downstream molecular mechanisms were characterized by non-target metabolomics and multiplex immunohistochemical staining. RNA sequencing was performed to evaluate the genetic alterations in various genes within the MenSCs.
MenSC-secreted ECM1 exhibits potential to ameliorate liver fibrosis by inactivating HSCs, improving liver functions, and reducing collagen deposition in both cellular and mouse model of the CCl4-induced liver fibrosis. Mechanistically, a novel interaction was identified that ECM1 directly bound to cell surface receptor LRP1α. Notably, the antifibrotic efficacy of MenSC was negated in LRP1-deficient cells and mice. Moreover, the ECM1-LRP1 axis contributed to the alleviation of liver fibrosis by suppressing AKT/mTOR while activating the FoxO1 signaling pathway, thereby facilitating pyrimidine and purine metabolism. Additionally, ECM1-modified MenSCs regulate the transcription of intrinsic cytokine genes, further mitigating liver fibrosis.
These findings highlight an extensive network of ECM1-LRP1 interaction, which serve as a link for providing promising insights into the mechanism of MenSC-based drug development for liver fibrosis. Our study also potentially presents novel avenues for clinical antifibrotic therapy.
© 2025. The Author(s).

This study aimed to investigate the therapeutic effect of human nasal turbinate-derived stem cells (hNTSCs) on mice with rheumatoid arthritis (RA) and identify hNTSC gene signatures with therapeutic effects on RA. hNTSCs were obtained from 20 healthy controls (HCs) who had undergone nasal turbinate surgery. Collagen-induced arthritis (CIA) mice were used to investigate the therapeutic effects of hNTSCs. The engraftment and migration abilities of hNTSCs were evaluated. CD4+CD25- T cells were co-cultured with hNTSCs, and effector T cell proliferation was evaluated by flow cytometry. Osteoclast differentiation was evaluated using mouse bone marrow monocytes which were cultured with M-CSF and RANKL, then TRAP staining was performed to measure effect of hNTSCs on osteoclastogenesis. Microarray assays were performed to identify gene expression differences between hNTSCs with CIA mice therapeutic or not and were validated by RT-qPCR. hNTSCs differentiated well into osteoblasts and adipocytes and expressed high levels of CXCL1 and osteoprotegerin. Single-cell RNA sequencing showed that hNTSCs clustered into 11 cell types, and cell surface markers were compatible with mesenchymal stem cells. hNTSC-treated CIA mice showed reductions in arthritis severity scores and incidence of arthritis. In engraft measurements, hNTSCs survived for 8 to 12 weeks in mice paws. Chemokine receptors expression increased in hNTSCs by IL-1β or TNF-α stimulation. CD4+CD25- T cell proliferation was reduced by hNTSCs and reversed by adding 1-MT (indoleamine 2,3-dioxygenase inhibitor), indicating that indoleamine 2,3-dioxygenase mediated T cell suppression. Osteoclastogenesis was suppressed by hNTSCs, and this was attenuated by anti-OPG Ab. hNTSCs therapeutic in CIA mice showed specific gene signatures with up-regulated genes (KRTAP1-5, HAS2, and CXCL1) and down-regulated genes (GSTT2B and C4B) compared to hNTSCs without CIA therapeutic effects. hNTSCs exhibited therapeutic potential in RA. Therapeutic effects were mediated by effector helper T cell suppression and the inhibition of osteoclastogenesis. In addition, hNTSCs with greater therapeutic effects on RA showed significant differences in their gene signatures.
© 2025. The Author(s).