Liver-derived human mesenchymal stem cells: a novel therapeutic source for liver diseases

Wang, Yini; Yu, Xiaopeng; Chen, Ermei; Li, Lanuan

doi:10.1186/s13287-016-0330-3

Cited by 65 publications

(49 citation statements)

References 82 publications

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“…Although the current study is not the first attempt at characterizing the L-MSCs, (48) it differs from and extends the results of the previous ones significantly. Mainly, we investigated MSCs obtained from primary adult human liver tissue, rather than infant liver, (49) cryopreserved hepatocytes, (50) or liver allograft perfusate as a source.…”

Section: L-mscs Possess Characteristics That Define Othercontrasting

confidence: 45%

Phenotypic, Transcriptional, and Functional Analysis of Liver Mesenchymal Stromal Cells and Their Immunomodulatory Properties

et al. 2020

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The liver is an immunologically active organ with a tolerogenic microenvironment at a quiescent state. The immunoregulatory properties of the liver appear to be retained after transplantation because liver allografts can reduce alloresponses against other organs that are simultaneously transplanted. Mechanisms of this phenomenon remain unknown. Given the known immunomodulatory properties of mesenchymal stromal cells (MSCs), we hypothesized that liver mesenchymal stromal cells (L‐MSCs) are superior immunomodulators and contribute to liver‐mediated tolerance. L‐MSCs, generated from human liver allograft biopsies, were compared with adipose mesenchymal stromal cells (A‐MSCs) and bone marrow mesenchymal stromal cells (BM‐MSCs). Trilineage differentiation of L‐MSCs was confirmed by immunohistochemistry. Comparative phenotypic analyses were done by flow cytometry and transcriptome analyses by RNA sequencing in unaltered cell cultures. The in vitro functional analyses were performed using alloreactive T cell proliferation assays. The transcriptome analysis showed that the L‐MSCs are different than the A‐MSCs and BM‐MSCs, with significant enrichment of genes and gene sets associated with immunoregulation. Compared with the others, L‐MSCs were found to express higher cell surface levels of several select immunomodulatory molecules. L‐MSCs (versus A‐MSCs/BM‐MSCs) inhibited alloreactive T cell proliferation (22.7% versus 56.4%/58.7%, respectively; P < 0.05) and reduced the frequency of interferon ɤ–producing T cells better than other MSCs (52.8% versus 94.4%/155.4%; P < 0.05). The antiproliferative impact of L‐MSCs was not dependent on cell‐to‐cell contact, could be reversed incompletely by blocking programmed death ligand 1, and required a higher concentration of the competitive inhibitor of indoleamine 2,3‐dioxygenase for complete reversal. In conclusion, L‐MSCs appear to be uniquely well‐equipped immunomodulatory cells, and they are more potent than A‐MSCs and BM‐MSCs in that capacity, which suggests that they may contribute to liver‐induced systemic tolerance.

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Section: L-mscs Possess Characteristics That Define Othercontrasting

confidence: 45%

Phenotypic, Transcriptional, and Functional Analysis of Liver Mesenchymal Stromal Cells and Their Immunomodulatory Properties

et al. 2020

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“…We now know that the assumption that MSCs are derived from the connective tissue (stroma) of marrow or the stroma of other tissues is not correct. This assumption became more untenable when reports came forth of MSCs isolation from almost every tissue of the body: Fat, skin, heart, muscle, liver, etc . The landmark and comprehensive report of Crisan et al clearly documents that MSCs are derived from perivascular cells (pericytes) from a number of human tissues.…”

Section: Pericytes As the Progenitor Of Mscsmentioning

confidence: 99%

New MSC: MSCs as pericytes are Sentinels and gatekeepers

Caplan

2017

J. Orthop. Res.

131

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Human Mesenchymal Stem Cells, hMSCs, were first named over 25 years ago with the "stem cell" nomenclature derived from the fact that we and others could cause these cells to differentiate into a number of different mesodermal phenotypes in cell culture. The capacity to form skeletal tissue in vitro encouraged the use of hMSCs for the fabrication of tissue engineered skeletal repair tissue with subsequent transplantation to in vivo sites. With the current realization that MSCs are derived from perivascular cells, pericytes, and the immunomodulatory and trophic capabilities of MSCs in both in vitro and in vivo test systems, a complete re-evaluation of the role and functions of MSCs in the body was required. Additionally, the skeleton is a preferred organ for cancer dissemination from various tumor malignancies. To date, most efforts to understand skeletal metastasis have focused on the invasive and digestive capability of disseminated tumor cells (DTCs). The contribution of the target organ-specific microvascular structure influencing extravasation is less well understood. Current targeted cancer therapies are designed to alter not only biological functions in DTCs, but also components of the tumor stroma/microenvironment such as blood vessels. We now have a comprehensive image of the critical role of the host vasculature as an instructive niche for DTCs. The focus of this manuscript is to present the current information about MSC function in situ and to emphasize how these new observations provide insight into understanding the role of the pericyte/MSC in skeletal activities including our new hypothesis for how these cells act as a gatekeeper for metastasis of melanoma into bone. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1151-1159, 2017.

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“…Thus, it is plausible that the increased liver colonization is regulated by the MSX1-ZEB1 axis. Furthermore, the hepatic microenvironment provides a favorable milieu for mesenchymal stem cells, which likely play a role in the promotion of liver regeneration (Liu et al, 2015; Wang et al, 2016). …”

Section: Discussionmentioning

confidence: 99%

MSX1-Induced Neural Crest-Like Reprogramming Promotes Melanoma Progression

Heppt

Wang

Hristova

et al. 2018

Journal of Investigative Dermatology

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Melanoma cells share many biological properties with neural crest stem cells. Here we show that the homeodomain transcription factor MSX1, which is significantly correlated with melanoma disease progression, reprograms melanocytes and melanoma cells toward a neural crest precursor-like state. MSX1-reprogrammed normal human melanocytes express the neural crest marker p75 and become multipotent. MSX1 induces a phenotypic switch in melanoma, which is characterized by an oncogenic transition from an E-cadherin—high nonmigratory state toward a ZEB1-high invasive state. ZEB1 up-regulation is responsible for the MSX1-induced migratory phenotype in melanoma cells. Depletion of MSX1 significantly inhibits melanoma metastasis in vivo. These results show that neural crest-like reprogramming achieved by a single factor is a critical process for melanoma progression.

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Liver-derived human mesenchymal stem cells: a novel therapeutic source for liver diseases

Cited by 65 publications

References 82 publications

Phenotypic, Transcriptional, and Functional Analysis of Liver Mesenchymal Stromal Cells and Their Immunomodulatory Properties

Phenotypic, Transcriptional, and Functional Analysis of Liver Mesenchymal Stromal Cells and Their Immunomodulatory Properties

New MSC: MSCs as pericytes are Sentinels and gatekeepers

MSX1-Induced Neural Crest-Like Reprogramming Promotes Melanoma Progression

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