Biologic and immunomodulatory properties of mesenchymal stromal cells derived from human pancreatic islets

Kim, Jaehyup; Breunig, Melissa J.; Escalante, Leah E.; Bhatia, Neehar; Denu, Ryan A.; Dollar, Bridget A.; Stein, Andrew P.; Hanson, Summer E.; Naderi, Nadia; Radek, James T.; Haughy, Dermot; Bloom, Debra D.; Assadi‐Porter, Fariba M.; Hematti, Peiman

doi:10.3109/14653249.2012.684376

Cited by 27 publications

(15 citation statements)

References 56 publications

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“…According to the original studies of Friedenstein and Pittenger [38,39], we used their physical property of plastic adherence to isolate adherent cells from human pancreatic islet. To overcome the limited access of human pancreatic islets and the early senescence highlighted in pancreatic human MSCs after ten passages [40,41], we immortalized islet-derived cells by using hTERT-expressing retrovirus.…”

Section: Discussionmentioning

confidence: 99%

Characterization of immortalized human islet stromal cells reveals a MSC-like profile with pancreatic features

et al. 2020

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Background: Mesenchymal stromal cells (MSCs) represent an interesting tool to improve pancreatic islet transplantation. They have immunomodulatory properties and secrete supportive proteins. However, the functional properties of MSCs vary according to many factors such as donor characteristics, tissue origin, or isolation methods. To counteract this heterogeneity, we aimed to immortalize and characterize adherent cells derived from human pancreatic islets (hISCs), using phenotypic, transcriptomic, and functional analysis. Methods: Adherent cells derived from human islets in culture were infected with a hTERT retrovirus vector and then characterized by microarray hybridization, flow cytometry analysis, and immunofluorescence assays. Osteogenic, adipogenic, and chondrogenic differentiation as well as PBMC proliferation suppression assays were used to compare the functional abilities of hISCs and MSCs. Extracellular matrix (ECM) gene expression profile analysis was performed using the SAM (Significance Analysis of Microarrays) software, and protein expression was confirmed by western blotting. Results: hISCs kept an unlimited proliferative potential. They exhibited several properties of MSCs such as CD73, CD90, and CD105 expression and differentiation capacity. From a functional point of view, hISCs inhibited the proliferation of activated peripheral blood mononuclear cells. The transcriptomic profile of hISCs highly clusterized with bone marrow (BM)-MSCs and revealed a differential enrichment of genes involved in the organization of the ECM. Indeed, the expression and secretion profiles of ECM proteins including collagens I, IV, and VI, fibronectin, and laminins, known to be expressed in abundance around and within the islets, were different between hISCs and BM-MSCs. Conclusion: We generated a new human cell line from pancreatic islets, with MSCs properties and retaining some pancreatic specificities related to the production of ECM proteins. hISCs appear as a very promising tool in islet transplantation by their availability (as a source of inexhaustible source of cells) and ability to secrete a supportive "pancreatic" microenvironment.

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Section: Discussionmentioning

confidence: 99%

Characterization of immortalized human islet stromal cells reveals a MSC-like profile with pancreatic features

et al. 2020

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“…Both IL1b and IL6 may be expressed in MSCs [27,57,58]. IL1b is regarded as a typical NF-kB activator for long time, and its elevation potently supports the NF-kB activation.…”

Section: Discussionmentioning

confidence: 99%

Transcriptional Profiling Reveals Crosstalk Between Mesenchymal Stem Cells and Endothelial Cells Promoting Prevascularization by Reciprocal Mechanisms

LiJunxiang

MaYing

TengRuifang

et al. 2015

Stem Cells and Development

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Mesenchymal stem cells (MSCs) show great promise in blood vessel restoration and vascularization enhancement in many therapeutic situations. Typically, the co-implantation of MSCs with vascular endothelial cells (ECs) is effective for the induction of functional vascularization in vivo, indicating its potential applications in regenerative medicine. The effects of MSCs-ECs-induced vascularization can be modeled in vitro, providing simplified models for understanding their underlying communication. In this article, a contact coculture model in vitro and an RNA-seq approach were employed to reveal the active crosstalk between MSCs and ECs within a short time period at both morphological and transcriptional levels. The RNA-seq results suggested that angiogenic genes were significantly induced upon coculture, and this prevascularization commitment might require the NF-kB signaling. NF-kB blocking and interleukin (IL) neutralization experiments demonstrated that MSCs potentially secreted IL factors including IL1b and IL6 to modulate NF-kB signaling and downstream chemokines during coculture. Conversely, RNA-seq results indicated that the MSCs were regulated by the coculture environment to a smooth muscle commitment within this short period, which largely induced myocardin, the myogenic co-transcriptional factor. These findings demonstrate the mutual molecular mechanism of MSCs-ECs-induced prevascularization commitment in a quick response.

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“…The islet-derived cells are more effective at suppressing lymphocyte proliferation. Thus donor banks of islet-derived mesenchymal stromal cells may be a more useful feeder-layer for ex vivo islet culture or to provide a more suitable islet microenvironment after transplantation [101]. …”

Section: β-Cell Death and T1dmentioning

confidence: 99%

Metabolomics applied to the pancreatic islet

Gooding

Jensen

Newgard

2016

Archives of Biochemistry and Biophysics

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Metabolomics, the characterization of the set of small molecules in a biological system, is advancing research in multiple areas of islet biology. Measuring a breadth of metabolites simultaneously provides a broad perspective on metabolic changes as the islets respond dynamically to metabolic fuels, hormones, or environmental stressors. As a result, metabolomics has the potential to provide new mechanistic insights into islet physiology and pathophysiology. Here we summarize advances in our understanding of islet physiology and the etiologies of type-1 and type-2 diabetes gained from metabolomics studies.

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Biologic and immunomodulatory properties of mesenchymal stromal cells derived from human pancreatic islets

Cited by 27 publications

References 56 publications

Characterization of immortalized human islet stromal cells reveals a MSC-like profile with pancreatic features

Characterization of immortalized human islet stromal cells reveals a MSC-like profile with pancreatic features

Transcriptional Profiling Reveals Crosstalk Between Mesenchymal Stem Cells and Endothelial Cells Promoting Prevascularization by Reciprocal Mechanisms

Metabolomics applied to the pancreatic islet

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