Genetic lineage tracing reveals stellate cells as contributors to myofibroblasts in pancreas and islet fibrosis

Wang, Jinbang; Li, Tingting; Zhou, Yunting; Wang, Xiaohang; Carvalho, Vladmir; Ni, Chengming; Li, Wei; Wang, Qianqian; Chen, Yang; Shang, Zhanjia; Qiu, Shanhu; Sun, Zilin

doi:10.1016/j.isci.2023.106988

Cited by 2 publications

(2 citation statements)

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“…7 Pancreatic Stellate Cells (PSCs) were first identified in 1998, 8 and have since been implicated in the development of pancreatitis, pancreatic fibrosis, pancreatic cancer, and in normal pancreas development. 9,10 PSCs express stromal cell markers and are multipotent. 11 Previous studies have reported the existence of stromal cell populations within the endocrine pancreatic islets which were referred to as isletderived fibroblast-like cells, 12 islet-derived precursors, 13 or islet-derived progenitor cells, 14 but the precise identity and biological properties of these populations have not yet been studied in detail.…”

Section: Introductionmentioning

confidence: 99%

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Mouse islet‐derived stellate cells are similar to, but distinct from, mesenchymal stromal cells and influence the beta cell function

Xu,

Zhou,

Wang

et al. 2024

Diabet Med

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AimsEvidence is accumulating of the therapeutic benefits of mesenchymal stromal cells (MSCs) in diabetes‐related conditions. We have identified a novel population of stromal cells within islets of Langerhans – islet stellate cells (ISCs) – which have a similar morphology to MSCs. In this study we characterize mouse ISCs and compare their morphology and function to MSCs to determine whether ISCs may also have therapeutic potential in diabetes.MethodsISCs isolated from mouse islets were compared to mouse bone marrow MSCs by analysis of cell morphology; expression of cell‐surface markers and extracellular matrix (ECM) components; proliferation; apoptosis; paracrine activity; and differentiation into adipocytes, chondrocytes and osteocytes. We also assessed the effects of co‐culture with ISCs or MSCs on the insulin secretory capacity of islet beta cells.ResultsAlthough morphological similar, ISCs were functionally distinct from MSCs. Thus, ISCs were less proliferative and more apoptotic; they had different expression levels of important paracrine factors; and they were less efficient at differentiation down multiple lineages. Co‐culture of mouse islets with ISCs enhanced glucose induced insulin secretion more effectively than co‐culture with MSCs.ConclusionsISCs are a specific sub‐type of islet‐derived stromal cells that possess biological behaviors distinct from MSCs. The enhanced beneficial effects of ISCs on islet beta cell function suggests that they may offer a therapeutic target for enhancing beta cell functional survival in diabetes.

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Section: Introductionmentioning

confidence: 99%

“…Pancreatic Stellate Cells (PSCs) were first identified in 1998, 8 and have since been implicated in the development of pancreatitis, pancreatic fibrosis, pancreatic cancer, and in normal pancreas development 9,10 . PSCs express stromal cell markers and are multipotent 11 .…”

Section: Introductionmentioning

confidence: 99%

Mouse islet‐derived stellate cells are similar to, but distinct from, mesenchymal stromal cells and influence the beta cell function

Xu,

Zhou,

Wang

et al. 2024

Diabet Med

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Human pancreatic islet-derived stromal cells reveal combined features of mesenchymal stromal cells and pancreatic stellate cells

Ebrahim,

Kondratyev,

Artyuhov

et al. 2024

Stem Cell Res Ther

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Background Mesenchymal stromal cells (MSCs) are recognized for their potential in regenerative medicine, attributed to their multipotent differentiation capabilities and immunomodulatory properties. Despite this potential, the classification and detailed characterization of MSCs, especially those derived from specific tissues like the pancreas, remains challenging leading to a proliferation of terminology in the literature. This study aims to address these challenges by providing a thorough characterization of human pancreatic islets-derived mesenchymal stromal cells (hPD-MSCs). Methods hPD-MSCs were isolated from donor islets using enzymatic digestion, immortalized through lentiviral transduction of human telomerase reverse transcriptase (hTERT). Cells were characterized by immunostaining, flow cytometry and multilineage differentiation potential into adipogenic and osteogenic lineages. Further a transcriptomic analysis was done to compare the gene expression profiles of hPD-MSCs with other mesenchymal cells. Results We show that hPD-MSCs express the classical MSC features, including morphological characteristics, surface markers expression (CD90, CD73, CD105, CD44, and CD106) and the ability to differentiate into both adipogenic and osteogenic lineages. Furthermore, transcriptomic analysis revealed distinct gene expression profiles, showing notable similarities between hPD-MSCs and pancreatic stellate cells (PSCs). The study also identified specific genes that distinguish hPD-MSCs from MSCs of other origins, including genes associated with pancreatic function (e.g., ISL1) and neural development (e.g., NPTX1, ZNF804A). A novel gene with an unknown function (ENSG00000286190) was also discovered. Conclusions This study enhances the understanding of hPD-MSCs, demonstrating their unique characteristics and potential applications in therapeutic strategies. The identification of specific gene expression profiles differentiates hPD-MSCs from other mesenchymal cells and opens new avenues for research into their role in pancreatic function and neural development. Supplementary Information The online version contains supplementary material available at 10.1186/s13287-024-03963-2.

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Genetic lineage tracing reveals stellate cells as contributors to myofibroblasts in pancreas and islet fibrosis

Cited by 2 publications

References 45 publications

Mouse islet‐derived stellate cells are similar to, but distinct from, mesenchymal stromal cells and influence the beta cell function

Mouse islet‐derived stellate cells are similar to, but distinct from, mesenchymal stromal cells and influence the beta cell function

Human pancreatic islet-derived stromal cells reveal combined features of mesenchymal stromal cells and pancreatic stellate cells

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