Alternative origins of stroma in normal organs and disease

Kolonin, Mikhail G.; Evans, Kurt W.; Mani, Sendurai A.; Gomer, Richard H.

doi:10.1016/j.scr.2011.11.005

Cited by 53 publications

(55 citation statements)

References 126 publications

(190 reference statements)

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“…A bone marrow transplantation model for tracking WATderived cells To enable tracking of hematopoietic tumor stroma (17,18,35,36) in parallel with ASCs, we designed an in vivo competitive repopulation assay. This obesity/cancer model is based on 2 syngeneic mouse strains: host ubiquitously expressing GFP and donor expressing RFP.…”

Section: Obesity-associated Cell Mobilization and Tumor Infiltrationmentioning

confidence: 99%

“…[13][14][15]. ASCs are similar to mesenchymal stromal cells (MSC) originally isolated as bone marrow colony-forming unit (CFU-F) fibroblasts (16,17). Accumulating evidence indicates that MSCs serve as progenitors of cells contributing to the trophic tumor microenvironment (18)(19)(20)(21).…”

Section: Introductionmentioning

confidence: 99%

“…Administered bone marrow MSC and ASC engraft tumors in animal models result in accelerated cancer progression (7,(22)(23)(24); however, the physiologic relevance of these results has been unclear. The capacity of mesenchymal progenitors to sense cancer as a site of hypoxia/inflammation has been proposed to explain their tumor homing (17,25). ASC proliferation accompanies WAT expansion (26) and number of ASCs per gram of WAT increases in obese individuals (27,28).…”

Section: Introductionmentioning

confidence: 99%

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Stromal Progenitor Cells from Endogenous Adipose Tissue Contribute to Pericytes and Adipocytes That Populate the Tumor Microenvironment

et al. 2012

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Epidemiologic studies associate cancer with obesity, but the pathophysiologic connections remain obscure. In this study, we show that obesity facilitates tumor growth in mice irrespective of concurrent diet, suggesting a direct effect of excess white adipose tissue (WAT). When transplanted into mice, adipose stromal cells (ASC) can serve as perivascular adipocyte progenitors that promote tumor growth, perhaps helping explain the obesitycancer link. In developing this hypothesis, we showed that ASCs are expanded in obesity and that they traffic from endogenous WAT to tumors in several mouse models of cancer. Strikingly, a comparison of circulating and tumorinfiltrating cell populations in lean, and obese mice revealed that cancer induces a six-fold increase of ASC frequency in the systemic circulation. We obtained evidence that ASCs mobilized in this way can be recruited into tumors, where they can be incorporated into blood vessels as pericytes and they can differentiate into adipocytes in an obesity-dependent manner. Extending this evidence, we found that increased tumor vascularization (reflected by changes in tumor vascular morphology and a two-fold increase in vascular density) was associated with intratumoral adipocytes and elevated proliferation of neighboring malignant cells. Taken together, our results suggest that ASCs recruited from endogenous adipose tissue can be recruited by tumors to potentiate the supportive properties of the tumor microenvironment. Cancer Res; 72(20); 5198-208. Ó2012 AACR.

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Section: Obesity-associated Cell Mobilization and Tumor Infiltrationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Stromal Progenitor Cells from Endogenous Adipose Tissue Contribute to Pericytes and Adipocytes That Populate the Tumor Microenvironment

et al. 2012

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“…MSC are not only capable of differentiating into adipocytes, osteoblasts, and chondrocytes, which has resulted in the term mesenchymal stem cells, 6,7 but also support vascularization as trophic pericytic cells and suppress the immune response. 8 These combined features have made bone marrow MSC as a cell type of choice for numerous clinical trials that are currently in progress. In the meanwhile, organs such as WAT have been shown as a considerably more abundant reservoir of mesenchymal progenitors.…”

mentioning

confidence: 99%

“…[16][17][18][19] ASC promote endothelial proliferation and blood vessel formation at least in part via trophic effects of secreted growth factors, while also displaying marked anti-inflammatory properties. 8 These features of WAT have made grafts of adipose tissue fragments or cells (lipotransfer) a promising approach to cosmetic and functional tissue repair. 20 In parallel, approaches to de novo tissue engineering based on ASC have been developed.…”

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confidence: 99%

Adipose Tissue Engineering in Three-Dimensional Levitation Tissue Culture System Based on Magnetic Nanoparticles

Daquinag

Souza²,

Kolonin³

2013

Tissue Engineering Part C: Methods

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White adipose tissue (WAT) is becoming widely used in regenerative medicine/cell therapy applications, and its physiological and pathological importance is increasingly appreciated. WAT is a complex organ composed of differentiated adipocytes, stromal mesenchymal progenitors known as adipose stromal cells (ASC), as well as endothelial vascular cells and infiltrating leukocytes. Two-dimensional (2D) culture that has been typically used for studying adipose cells does not adequately recapitulate WAT complexity. Improved methods for reconstruction of functional WAT ex vivo are instrumental for understanding of physiological interactions between the composing cell populations. Here, we used a three-dimensional (3D) levitation tissue culture system based on magnetic nanoparticle assembly to model WAT development and growth in organoids termed adipospheres. We show that 3T3-L1 preadipocytes remain viable in spheroids for a long period of time, while in 2D culture, they lose adherence and die after reaching confluence. Upon adipogenesis induction in 3T3-L1 adipospheres, cells efficiently formed large lipid droplets typical of white adipocytes in vivo, while only smaller lipid droplet formation is achievable in 2D. Adiposphere-based coculture of 3T3-L1 preadipocytes with murine endothelial bEND.3 cells led to a vascular-like network assembly concomitantly with lipogenesis in perivascular cells. Adipocyte-depleted stromal vascular fraction (SVF) of mouse WAT cultured in 3D underwent assembly into organoids with vascular-like structures containing luminal endothelial and perivascular stromal cell layers. Adipospheres made from primary WAT cells displayed robust proliferation and complex hierarchical organization reflected by a matricellular gradient incorporating ASC, endothelial cells, and leukocytes, while ASC quickly outgrew other cell types in adherent culture. Upon adipogenesis induction, adipospheres derived from the SVF displayed more efficient lipid droplet accumulation than 2D cultures. This indicates that 3D intercellular signaling better recapitulates WAT organogenesis. Combined, our studies show that adipospheres are appropriate for WAT modeling ex vivo and provide a new platform for functional screens to identify molecules bioactive toward individual adipose cell populations. This 3D methodology could be adopted for WAT transplantation applications and aid approaches to WAT-based cell therapy.

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Fibroblast autophagy in fibrotic disorders

Principe¹,

Lista

Malorni

et al. 2012

The Journal of Pathology

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Fibrotic disorders are multistage progressive processes that often arise from different causes and are commonly associated with chronic inflammation. Excessive deposition of extracellular matrix is the hallmark of many fibrotic diseases. This may be due to an excess of fibroblast recruitment and activation, as well as to their differentiation in myofibroblasts. These events may be triggered by cytokines, chemokines and growth factors released by lymphocytes or macrophages. The excessive production of extracellular matrix is apparently due to alterations of metabolic pathways in activated fibroblasts. It has been suggested that a defective autophagy, an important subcellular pathway with multiple homeostatic roles, also recognized as a key component of both innate and acquired immunity, could play a role. In this review we illustrate recent insights in the field, suggesting the possible implication of the immune system in orchestrating the fibrotic response via the modulation of autophagic pathways.

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Alternative origins of stroma in normal organs and disease

Cited by 53 publications

References 126 publications

Stromal Progenitor Cells from Endogenous Adipose Tissue Contribute to Pericytes and Adipocytes That Populate the Tumor Microenvironment

Stromal Progenitor Cells from Endogenous Adipose Tissue Contribute to Pericytes and Adipocytes That Populate the Tumor Microenvironment

Adipose Tissue Engineering in Three-Dimensional Levitation Tissue Culture System Based on Magnetic Nanoparticles

Fibroblast autophagy in fibrotic disorders

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