Current Stem Cell Research & Therapy - Volume 20, Issue 6, 2025

Diabetes Mellitus (DM) can lead to serious complications, such as Diabetic Foot Ulcers (DFUs). Currently, Aquacel Extra is one of the standard therapies for DFUs, but its efficacy has some limitations that may be overcome by alternative treatments, such as the secretome derived from adipose-derived stem cell (ADSCs). ADSC secretome has shown promising results in promoting wound healing by enhancing cell proliferation, collagen synthesis, and migration of fibroblasts.

This study aims to compare the effect of the adipose-derived stem cell (ADSC) secretome to Aquacel Extra, a hydrofiber dressing containing gel- forming agents, on wound healing in a diabetic rat model. Aquacel Extra has sodium carboxymethylcellulose fibers, which contribute to its unique properties.

The objective of this study is to compare the wound healing outcome of ADSC secretome and Aquacel Extra in streptozotocin-induced diabetic rats.

Sprague Dawley rats received a single intravenous administration of streptozotocin to induce diabetes mellitus (DM). A full-thickness excisional circular wound was created at the dorsum aspect of the rats two weeks after diabetic induction. Rats were randomly divided into two groups: the Aquacel Extra group, which received the hydrofiber dressing Aquacel Extra containing gel-forming agents, and the secretome group, which received the ADSC secretome on days 0, 3, and 7. The gross examination was performed on days 0, 3, 7, and 14. On day 14, the rats were euthanized, and full-thickness skin biopsies of the wounds were taken for histological and immunohistochemical analysis.

The secretome group demonstrated accelerated cutaneous wound healing compared to the Aquacel Extra group, as indicated by faster wound closure (p < 0.05). Hematoxylin and eosin staining revealed a thicker epidermal layer in the secretome group than in the Aquacel Extra group (p < 0.05). The mean histological score of the secretome group was higher at 10 ± 1.73 compared to the score of 8.33 ± 1.52 in the Aquacel Extra group, indicating a more mature tissue architecture. Immunohistochemical analysis showed lower expression of α-smooth muscle actin (α-sma) in the secretome group than in the Aquacel Extra group, which correlated with reduced collagen secretion and deposition in the secretome group, as indicated by Masson’s trichrome staining.

The ADSC secretome accelerated the healing of diabetic wounds compared to Aquacel Extra. However, as this study is preliminary, future studies should be conducted similar to this study with a larger sample and wound size. In addition, the optimal dosage of ADSC secretome and the components of the secretome that promoted wound healing should be determined to fully elucidate the clinical potential of ADSC secretome.

The use of decellularized tissues as cell culture scaffolds is an exciting new direction in regenerative medicine because they may provide the instructional context for cell development and function.

Building a scaffold with biomimetic chemical, structural, and functional features is crucial for lung tissue healing. Due to the diverse nature of their structure, a decellularized lung matrix derived from both allogeneic and xenogeneic sources is regarded as an ideal scaffold for lung regeneration.

By decellularizing rat lungs using a combination of chemical and physical methods, we were able to build a scaffold for lung tissue engineering. A decellularized lung was tested for DNA content, and histologically, it was shown to be totally free of cells after using this process.

The decellularized lung was biocompatible for the growth of human endometrial stem cells (hEnSCs), as evidenced by scanning electron microscopy (SEM), an MTS assay, and Hematoxylin and Eosin (H&E) staining. In addition, we found that decellularized scaffolds induced lung epithelial cell differentiation from EnSCs by upregulating a subset of genes. Lung epithelial cell development from stem cells was also induced by decellularized scaffolds, as shown by an increase in the expression of a gene that is only expressed in lung epithelial cells. The strong level of acellularized scaffold affinity for cell adhesion, proliferation, and growth was also shown to promote lung lesion regeneration in rats after four weeks of treatment, according to in vivo research.

In summary, the decellularized lung scaffold that has been developed offers a highly accurate framework for the effective restoration of lung tissues. These scaffolds prove to be valuable tools for investigating the mechanisms by which the tissue microenvironment facilitates the growth, differentiation, and function of lung epithelial-like cells, ultimately contributing to the beneficial outcomes of lung repair.

Acute respiratory distress syndrome (ARDS) poses a significant challenge as it lacks specific treatments and can occur due to various etiologies. Mesenchymal stem cells (MSCs) have emerged as a promising cell-based therapy for ARDS due to their immunomodulatory, anti-inflammatory, and anti-fibrotic properties. Despite encouraging findings from preclinical studies, clinical evidence supporting the efficacy of MSCs in non-COVID-19 ARDS remains insufficient.

We conducted a systematic search of three major databases (Web of Science Core Collection, Scopus, and PubMed) to identify original articles focusing on MSCs in non-COVID-19 ARDS. Subsequently, we employed the bibliometric package in R Studio to analyze and visualize bibliometric indicators derived from the retrieved articles.

Our analysis of 244 original studies revealed a notable trend in research on MSCs and non-COVID-19 ARDS. While the number of publications in this area saw an increase beginning in 2007, it exhibited a decline after 2019, with only 20 articles published in 2022. Notably, a significant proportion (131/244) of these studies originated from Chinese scholars. MSC derivatives emerged as a recent research focus due to their unique advantages as an alternative to MSCs. Specifically, umbilical cord/placental-derived MSCs have gained traction, surpassing the use of bone marrow-derived MSCs by 2022. The route of delivery is still mainly intravenous. Despite the potential advantages of the intratracheal route for lung-related diseases, the intravenous route remains the preferred mode of drug delivery.

Research on non-COVID-19 ARDS deserves further attention and investments. Existing studies have primarily focused on MSC derivatives that have shown clinical efficacy. Furthermore, umbilical cord/placental-derived MSCs are expected to replace traditional bone marrow-derived MSCs in research. Intratracheal delivery, which offers advantages for treating pulmonary diseases, still requires extensive experiments to validate.

DAND5 encodes a protein that acts as an antagonist to Nodal/TGF-β and Wnt pathways. A mouse knockout (KO) model has shown that this molecule is associated with left-right asymmetry and cardiac development, with its depletion causing heterotaxia and cardiac hyperplasia.

This study aimed to investigate the molecular mechanisms affected by the depletion of DAND5.

DAND5-KO and wild-type embryoid bodies (EBs) were used to assess genetic expression with RNA sequencing. To complement the expression results that pointed towards differences in epithelial to mesenchymal transition (EMT), we evaluated migration and cell attachment. Lastly, in vivo valve development was investigated, as it was an established model of EMT.

DAND5-KO EBs progress faster through differentiation. The differences in expression will lead to differences in the expression of genes involved with Notch and Wnt signalling pathways, as well as changes in the expression of genes encoding membrane proteins. Such changes were accompanied by lower migratory rates in DAND5-KO EBs, as well as higher concentrations of focal adhesions. Within valve development, DAND5 is expressed in the myocardium underlying future valve sites, and its depletion compromises correct valve structure.

The DAND5 range of action goes beyond early development. Its absence leads to significantly different expression patterns in vitro and defects in EMT and migration. These results have an in vivo translation in mouse heart valve development. Knowledge regarding the influence of DAND5 in EMT and cell transformation allows further understanding of its role in development, or even in some disease contexts, such as congenital heart defects.

Posthepatectomy liver failure leads to a poor prognosis in patients receiving hepatectomy treatment, and cell therapy can promote liver regeneration. In this study, we investigated the therapeutic potential of human amniotic epithelial cells (hAECs) in promoting liver regeneration after partial hepatectomy (PHx) and the underlying molecular mechanism.

We established a 70% PHx liver regeneration model, after which 5×10⁵ hAECs were injected into the tail vein of mice. The resulting liver function, weight, and immunohistochemistry data were analyzed to determine whether hAECs can promote liver regeneration. Then, we explored the possible mechanism by which hAECs promote liver regeneration after PHx through RNA sequencing. Finally, western blotting and immunofluorescence were used to confirm the discovered potential mechanism and signaling pathway involved.

The mice in the hAECs group displayed enhanced liver regeneration 48 hours after 70% PHx and the expression levels of cell proliferation-related proteins were significantly higher than those in the control group. RNA sequencing analysis revealed that the key signaling pathway through which hAECs promote liver regeneration is the FOXO3a pathway. Mechanistically, IL-6 activates FOXO3a through STAT3, thereby promoting liver autophagy to enhance liver regeneration after PHx. Finally, western blotting and immunofluorescence confirmed that the IL-6/STAT3/FOXO3a pathway promotes liver regeneration by activating autophagy.

These results suggest that hAECs treatment promoted liver regeneration after PHx through the IL-6/ STAT3/FOXO3a/autophagy pathway.

Mesenchymal Stem Cells (MSCs) are pivotal in immunomodulation, hematopoiesis, and tissue repair. The interplay between MSCs and the pathological microenvironment influences their proliferation and differentiation. Transforming Growth Factor-Beta 1 (TGF-β1) serves as a key cytokine in the MSC microenvironment. This study aimed to scrutinize the impact of TGF-β1 on human placenta-derived MSCs of fetal origin (fPMSCs) and elucidate its underlying mechanism.

fPMSCs were isolated, and surface markers were identified by flow cytometry. Cell proliferation in fPMSCs was assessed using Cell Counting Kit-8 (CCK-8) and 5-Ethynyl-2’-Deoxy Uridine (EdU). Apoptosis was detected via Annexin V/PI staining, and apoptosis-related proteins were detected by western blot. Endoplasmic reticulum (ER) stress-related proteins were detected by western blot, and Flou-4 AM staining was utilized to assess intracellular Ca²⁺ levels under TGF-β1 exposure. The impact of 4-PBA treatment on ER stress and apoptosis was assessed by western blot and Annexin V/PI staining. Additionally, the PERK and p-PERK expressions were evaluated via Western blot.

CCK-8 and EdU assays revealed inhibited proliferation of fPMSCs under TGF-β1 exposure. Annexin V/PI staining demonstrated a significant induction of apoptosis in fPMSCs following TGF-β1 treatment. Furthermore, TGF-β1 treatment significantly elevated intracellular Ca²⁺ levels and the expressions of GRP78, p-eIF2α, and CHOP. Interruption of ER stress with 4-PBA mitigated TGF-β1-induced apoptosis in fPMSCs. Moreover, TGF-β1 increased p-PERK expression. Inhibition of PERK autophosphorylation with GSK2606414 suppressed TGF-β1-induced apoptosis and ER stress in fPMSCs.

Our findings indicated that TGF-β1 induced ER stress-dependent apoptosis in fPMSCs through the PERK signaling pathway. These results offer insights into enhancing the therapeutic efficacy of fPMSCs by modulating TGF-β1-induced apoptosis.