International Journal of Translational Science

Editorial

2026-02-17T03:59:42+01:00

This exciting issue includes a series of papers with high impact on medicine. The issue of placenta regeneration is addressed by Greenberg et al. The group showed extracellular vesicles from healthy placenta stem cells being able to restore the function of placenta stem cells from preeclampsia. This study brings up the possibility of continual placenta regeneration during pregnancy. If so, the question is why such generation becomes pathological during preeclampsia. This question, as well as other questions from this study will be addressed by this and other groups. Nonetheless, this exciting report paves a path for an alternative therapy with extracellular vesicles for preeclampsia.

An important question that remains in the area of stem cell is the method of sustained multipotency. Sherman et al, systematically address a role for NFκB in multipotency. The authors show a role for NFκB in cell autonomous regulation of multipotency. This finding is interesting since the focused stem cells, mesenchymal, have been shown to elicit immune suppression within an inflammatory environment. Such environment is expected to have a predominance of inflammatory mediators such as cytokines, which could activate NFκB. In this regard, this study suggested both intrinsic and extrinsic regulation of NFκB to regulate multipotency.

The regulation of stem cell multipotency is complex. This network has been addressed with informatic study that shows how pseudogenes could regulate other molecules, leading to multipotency or differentiation. This informatic studies form the basis for bench studies to perform cause-effect relationship to unravel the role of stem cell pseudogenes.

In light of cancer stem cells in solid and hematological malignancies, this issue continues its theme on translation. A short response to a published paper positively acknowledge the role of substance P in cancer. However, this topic is a pleasant revisit of seminal working showing a role for the evolutionary conserved peptide substance P in cancer. Overall, there is excitement since this study could lead to repurpose of a substance P receptor antagonist for cancer. There is a strong potential that such an antagonist will target the stem cell population.

Extracellular Vesicles from Healthy Placenta Stem Cells Restored the Immune Licensing Function of Preeclamptic Placenta Stem Cells

2026-02-17T03:22:04+01:00

Preeclampsia (PE) contributes to pregnancy-related morbidity and mortality, with enhanced inflammation. Healthy placenta stem cells (P-MSCs) can be licensed into immune suppressor cells to mitigate inflammation. Since PE is associated with inflammation, the question is why the associated P-MSCs cannot suppress the response. PE P-MSCs have been shown to be dysfunctional with respect to decreased anti-inflammatory response, cell cycle dysregulation, and reduced production of immune suppressive cytokines. Aspirin (ASA) treatment partly reversed these dysfunctions via epigenetic reprogramming. We tested the hypothesis that extracellular vesicles (EVs) from healthy P-MSC could reset PE P-MSCs to a healthy phenotype, including cell cycle dysregulation and anti-inflammatory licensing. EVs from healthy MSCs were collected and the number of particles quantified. The isolated EVs were added to PE P-MSCs. Control cultures treated the PE P-MSCs with 1 mM ASA. The treated cells were assessed for the epigene regulator TDG and cell cycle linked CDK4, p21, and p53 by western blot, or assessed as third-party suppression in a one-way mixed lymphocyte reaction (MLR). EV- and ASA-treated PE P-MSC suppressed MLR, similar to healthy P-MSCs. However, an evaluation of p21, CDK4, p53, and TDG suggested that EVs impart a more stable restoration of PE P-MSCs when exposed to healthy EVs. This study provides insights into the method by which healthy P-MSCs can function to restore PE P-MSCs, and in vivo microenvironmental restoration.

NFκB in Intrinsic and Cell Autonomous Regulation of Mesenchymal Stem Cell Multipotency

2026-02-17T03:29:48+01:00

Mesenchymal stem cells (MSCs) are multipotent stromal cells that can differentiate into cells of the three germ layers. MSCs exhibit immune plasticity and this property is guided by the inflammatory tissue niche. Importantly, MSCs can be licensed as immune suppressor cells within an inflammatory niche. Since MSCs are approved by the food and drug administration for particular inflammation, it is important to determine how these cells maintain multipotency, in particular, the fate of these cells in vivo when they become located within a varied tissue niche. More importantly, the molecular mechanisms by which MSCs maintain multipotency will improve clinical applications. The focus of this study is particularly important since MSCs are available off the shelf, indicating allogeneic differences between the recipient and donor. We studied the transcription factor NFκB since it is a central regulator of inflammation. NFκB also links intrinsic stem cell signaling and extrinsic inflammatory cues. We used in silico analyses and determined that NFκB could regulate the major stem cell genes such as Octamer 4A (Oct4A). We confirmed a canonical pathway using an NFκB array that dissected the intracellular pathway. Additionally, we used specific small molecules to inhibit NFκB subunits. Using published RNA-Seq data, we showed a potential role for the purinergic receptors with a key role for ADORA2B. Similar to the licensing of MSCs by inflammatory mediators, ADORA2B appeared to be regulated by growth factors, including those linked to inflammation. In total, NFκB regulates MSC multipotency in a cell-autonomous manner, explaining the licensing properties within an inflammatory microenvironment. We also showed that the purinergic receptors could be involved in intrinsic and extrinsic regulation of MSC multipotency.

Substance P/Neurokinin 1 Receptor Involvement in Breast Cancer Progression Supports Therapeutic Repurposing of the Drug Aprepitant

2026-02-17T03:44:57+01:00

This opinion article discusses the findings of a published article, which reported on the mechanism by which neuronal substance P (SP) drives metastasis through an extracellular RNA–TLR7 axis [1]. The role of SP in cancer is not a novel finding. Rather, SP’s effect on cancer is linked to a long-held view on the neural–hematopoietic axis. Since the article omitted several seminal findings, we organized this review/commentary that discusses the landscape of SP in breast cancer. We also include our collective thoughts on the cited article that mostly support the past literature. Our article is intended to enhance the field of the neural-substance P-cancer axis and applaud the authors for their exciting findings. We believe that their findings further underscore the need to target breast cancer with an SP receptor antagonist. In this regard, we propose repurposing of aprepitant to treat breast cancer.

Bioinformatics Analyses of Oct4 Pseudogenes

2026-02-17T03:52:09+01:00

Oct4 is among the key genes involved in pluripotency. Oct4, through alternative splicing, produces at least three different transcripts, Oct4a, Oct4b, and Oct4b1. The Oct4a transcript has been focused on due to its role in pluripotency and multipotency of stem cells. There are several Oct4 pseudogenes with at least seven identified in the human genome. Some of these Oct4 pseudogenes have been found in various cancers. The Oct4 pseudogenes share high homology to the Oct4a transcript. There is limited information on the biologic role of Oct4 pseudogenes. More importantly, it is unclear how these pseudogenes affect the biology of the full-length transcript. Thus, it is important to understand these pseudogenes since their biology could lead to a better understanding of differentiation, cancer, and dedifferentiation to form cancer stem cells. This brief report used in silico analyses to analyze Oct4 and its pseudogenes. The implication for the findings on stem cells and cancer, as well as other related genes, are discussed.