Human induced pluripotent stem cell-derived macrophages ameliorate liver fibrosis

Autor: Tatiana Kisseleva, Karin Diggle, Timothy V. Pham, Pablo Tamayo, Dan S. Kaufman, Andrea Fanjul, Hamidreza Hashemi, Luisjesus S. Cruz, Manuel Fierro, Somayeh Pouyanfard, Nairika Meshgin
Rok vydání: 2021
Předmět:
Liver Cirrhosis
Technology
induced pluripotent stem cells
Chronic Liver Disease and Cirrhosis
Immunology
Induced Pluripotent Stem Cells
Biology
Stem cell marker
liver
Regenerative Medicine
Medical and Health Sciences
Oral and gastrointestinal
Cell therapy
chemistry.chemical_compound
Mice
Rare Diseases
Fibrosis
medicine
Macrophage
2.1 Biological and endogenous factors
Animals
Humans
Induced pluripotent stem cell
liver regeneration
Sirius Red
Stem Cell Research - Induced Pluripotent Stem Cell
Stem Cell Research - Induced Pluripotent Stem Cell - Human
5.2 Cellular and gene therapies
Liver Disease
Inflammatory and immune system
Macrophages
Cell Differentiation
Cell Biology
cellular therapy
Biological Sciences
medicine.disease
Stem Cell Research
Liver regeneration
chemistry
Cancer research
Molecular Medicine
Cytokines
Digestive Diseases
CCL22
Developmental Biology
Zdroj: Stem cells (Dayton, Ohio), vol 39, iss 12
ISSN: 1549-4918
Popis: With an increasing number of patients with degenerative hepatic diseases, such as liver fibrosis, and a limited supply of donor organs, there is an unmet need for therapies that can repair or regenerate damaged liver tissue. Treatment with macrophages that are capable of phagocytosis and anti-inflammatory activities such as secretion of matrix metalloproteinases (MMPs) provide an attractive cellular therapy approach. Human induced pluripotent stem cells (iPSCs) are capable of efficiently generating a large-scale, homogenous population of human macrophages using fully defined feeder- and serum-free differentiation protocol. Human iPSC-macrophages exhibit classical surface cell markers and phagocytic activity similar to peripheral blood-derived macrophages. Moreover, gene and cytokine expression analysis reveal that these macrophages can be efficiently polarized to pro-inflammatory M1 or anti-inflammatory M2 phenotypes in presence of LPS + IFN-γ and IL-4 + IL-13, respectively. M1 macrophages express high level of CD80, TNF-α, and IL-6 while M2 macrophages show elevated expression of CD206, CCL17, and CCL22. Here, we demonstrate that treatment of liver fibrosis with both human iPSC-derived macrophage populations and especially M2 subtype significantly reduces fibrogenic gene expression and disease associated histological markers including Sirius Red, αSMA and desmin in immunodeficient Rag2−/−γc−/− mice model, making this approach a promising cell-based avenue to ameliorate fibrosis.
Databáze: OpenAIRE
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