CLL-Derived Exosomes Reprogram Resident Cells to Become CLL Supportive Cells

The lack of clinically relevant sinoatrial node (SAN) disease model makes the pathophysiological investigation and therapeutic development stagnant. We hypothesize that engineering SAN by TBX18 somatic-reprogrammed cardiomyocytes on the three-dimension (3D) scaffold could create an in vitro SAN model, sharing similar features with a native SAN. Methods: In addition to neonatal rat ventricular cardiomyocytes (NRVMs) alone, we chose cardiosphere-derived cells (CDCs), or fibroblasts as supportive cells with different mixing ratios to construct engineered SAN. Hydrogel scaffolds including matrigels or platelet gels were used and compared. The engineered tissue was reprogrammed by TBX18 over-expression. Results: The over-expression of TBX18 increased HCN4 and CX45 transcriptions in cardiomyocytes. A stable spontaneous beating rate could be created in TBX18-reprogrammed engineered tissue, made of NRVMs and fibroblasts with matrigel scaffold (beating rate, TBX18 vs. control: 105.0 ± 10.7 bpm vs. 35.5±7.1 bpm, n=12, P<0.001). Although spontaneous beating could be observed in reprogrammed engineered tissues by NRVM alone, NRVM with CDCs, or NRVMs with CDCs and fibroblasts, the beating rates were not stable and slower. The beating rate in engineered tissue did not differ between scaffolds of matrigel and platelet gel. However, inter-experimental variation is higher in platelet gels, compared to matrigels. By immunofluorescent staining, an unique spatial distribution of NRVMs and fibroblasts was identified. NRVMs formed the central core of engineered tissues, encapsulated by fibroblasts, which was similar to a native SAN. The application of a sympathomimetic drug (epinephrine) doubled the beating rate of reprogrammed engineered tissue (P=0.02, n=6-8). Conclusions: A pilot model of engineered SAN was established by TBX18-reprogrammed cardiomyocytes. The supportive cells such as fibroblasts played an important role in tissue engineering of SAN.

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Rotenone-induced neurotoxicity in rat brain areas: A study on neuronal and neuronal supportive cells

Neuroscience ◽

10.1016/j.neuroscience.2012.10.034 ◽

2013 ◽

Vol 230 ◽

pp. 172-183 ◽

Cited By ~ 16

Author(s):

S. Swarnkar ◽

P. Goswami ◽

P.K. Kamat ◽

I.K. Patro ◽

S. Singh ◽

...

Keyword(s):

Rat Brain ◽

Brain Areas ◽

Supportive Cells

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CLL-283: CLL-Derived Exosomes Turn Endothelial Cells into CLL-Supportive Cells

Clinical Lymphoma Myeloma & Leukemia ◽

10.1016/s2152-2650(21)01757-2 ◽

2021 ◽

Vol 21 ◽

pp. S321-S322

Author(s):

Uri Rozovski ◽

Lian Lipshtein ◽

Zinab Sarsor ◽

Einat Beery ◽

Shaked Bogen ◽

...

Keyword(s):

Endothelial Cells ◽

Supportive Cells

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Micropatterned coculture of primary human hepatocytes and supportive cells for the study of hepatotropic pathogens

Nature Protocols ◽

10.1038/nprot.2015.128 ◽

2015 ◽

Vol 10 (12) ◽

pp. 2027-2053 ◽

Cited By ~ 69

Author(s):

Sandra March ◽

Vyas Ramanan ◽

Kartik Trehan ◽

Shengyong Ng ◽

Ani Galstian ◽

...

Keyword(s):

Human Hepatocytes ◽

Primary Human Hepatocytes ◽

Supportive Cells

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Macrophages: Supportive cells for tissue repair and regeneration

Immunobiology ◽

10.1016/j.imbio.2013.09.001 ◽

2014 ◽

Vol 219 (3) ◽

pp. 172-178 ◽

Cited By ~ 159

Author(s):

Bénédicte Chazaud

Keyword(s):

Tissue Repair ◽

Tissue Repair And Regeneration ◽

Supportive Cells

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Androgen Activity in the Primary and Metastatic Prostate Cancer Microenvironments Influences Disease Progression and Patient Outcomes

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.2068 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A1011-A1011

Author(s):

Damien Leach ◽

Alison Buxton ◽

Gilberto Serrano de Almeida ◽

Grant Buchanan ◽

Charlotte Lynne Bevan

Keyword(s):

Prostate Cancer ◽

Cancer Cells ◽

Patient Outcomes ◽

Gene Transcription ◽

Primary Site ◽

Transcriptional Responses ◽

Androgen Therapy ◽

Metastatic Sites ◽

Supportive Cells

Abstract Background: Cancers do not exist in isolation, surrounding tumours are supportive cells, which create the microenvironment in which cancer cells reside. In the prostate cancer (PCa), androgen receptor (AR) signalling in the surrounding fibroblasts is strikingly distinct from that within PCa cells, and has specific functions to produce, maintain, and modulate the extracellular matrix (ECM) which surrounds and interacts with PCa cells. The supportive cells of metastatic sites differ from those in the primary site and produce different types of cellular microenvironments. Since the advent of second generation anti-androgen therapy there has been an increase in the presence of liver metastasis. This project investigates how AR and anti-androgen therapy affect the prostate liver microenvironment and the subsequent effects on cancer. Results: Analysis of microenvironment of primary and metastatic sites indicates transcriptional responses distinct from that seen in PCa cells. This is exemplified by proliferation responses to androgen and anti-androgens in microenvironment cells being the reverse to that seen in Pca cells. Dichotomising microdissected PCa patient material of matched cancer and stromal tissue, based on stromal AR level shows distinct transcriptional profiles in the matched cancer cells. From previous studies, we know AR status in cancer adjacent fibroblasts (CAFs) of the primary tumor inversely associates with patient outcomes. Analysis of single cell CAFs and microdissected stromal samples points to a potential sub population of CAFs with this AR status. Conditioned media from liver and prostate fibroblast cells suggests that inactivation of AR signalling produces proliferative paracrine signals that can affect cancer cell growth. AR in primary site fibroblast and liver stellate cells regulates secretome and ECM production in the primary and metastatic site. Prostates and livers from enzalutamide treated mice showed changes in collagen fibres compared to control mice, as visualised by picro-direct-red staining. We cultured PCa cells within 3D-ECM microenvironments created in vitro from prostate fibroblasts or liver cells. The different 3D-ECM were able to produce changes in PCa cells, including gene transcription, intracellular signalling pathways, and proliferation and apoptotic responses. These data suggest that the responses of primary and metastatic microenvironments to androgens and anti-androgens can influence phosphorylation of intracellular pathways leading to alterations in gene transcription. Furthermore, the transcriptional responses of cancer cells in vitro to changes in microenvironmental AR signalling can be used to predict patient outcomes. Conclusions: Our data suggests that anti-AR therapy produces organ microenvironment-specific signals that influence the response of prostate cancer to treatments and affects patient outcomes.

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Glial fibrillary acidic protein and S-100 protein in pineal supportive cells: An electron microscopic study

Brain Research ◽

10.1016/0006-8993(84)90866-7 ◽

1984 ◽

Vol 304 (1) ◽

pp. 117-120 ◽

Cited By ~ 11

Author(s):

Howard R. Higley ◽

John A. McNulty ◽

Geoffrey Rowden

Keyword(s):

Glial Fibrillary Acidic Protein ◽

Microscopic Study ◽

Electron Microscopic Study ◽

Acidic Protein ◽

Electron Microscopic ◽

S 100 ◽

Supportive Cells

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A quantitative morphological study of the pineal organ in the goldfish, Carassius auratus

Canadian Journal of Zoology ◽

10.1139/z81-183 ◽

1981 ◽

Vol 59 (7) ◽

pp. 1312-1325 ◽

Cited By ~ 10

Author(s):

John A. McNulty

Keyword(s):

Endoplasmic Reticulum ◽

Pineal Organ ◽

Smooth Endoplasmic Reticulum ◽

Close Association ◽

Photoreceptor Cells ◽

Nerve Fibers ◽

Substantial Part ◽

Electron Microscopic ◽

Goldfish Carassius Auratus ◽

Supportive Cells

Stereological techniques applied to a light and electron microscopic study of the pineal organ of the goldfish indicated that photoreceptor and supportive cells were comparable in their number and cell volume and that approximately 500 nerve cells were present in the pineal end vesicle. There were approximately 310 nerve fibers descending the distal part of the pineal tract. Quantitative analysis of organelles in photoreceptor cells revealed that the endoplasmic reticulum and Golgi bodies, in the vicinity of which were situated both clear and dense-cored vesicles, formed a substantial part of the cytoplasmic volume. Other new observations reported for this species include a close association between mitochondria and parts of the smooth endoplasmic reticulum, a characteristic feature of photoreceptor cells, and the presence of subsurface cisternae formed from profiles of endoplasmic reticulum. Moreover, specialized contacts were found between both photoreceptor and supportive cells. Some of these ultrastructural features are similar to those reported in the secretory pinealocytes of mammals. These findings suggest that (1) the pineal organ in this species has a high degree of photosensitivity as evidenced by the large number of photoreceptor cells related to each nerve cell, and (2) photoreceptor cells are metabolically active possibly having functions other than photoreception.

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Mapping PrPSc Propagation in Experimental and Natural Scrapie in Sheep with Different PrP Genotypes

Veterinary Pathology ◽

10.1354/vp.42-3-258 ◽

2005 ◽

Vol 42 (3) ◽

pp. 258-274 ◽

Cited By ~ 37

Author(s):

C. Ersdal ◽

M. J. Ulvund ◽

A. Espenes ◽

S. L. Benestad ◽

P. Sarradin ◽

...

Keyword(s):

Nervous System ◽

Lymph Node ◽

Cellular Localization ◽

Clinical Signs ◽

Enzyme Linked Immunosorbent Assay ◽

Poor Correlation ◽

Peripheral Tissues ◽

The Central Nervous System ◽

Natural Scrapie ◽

Supportive Cells

Twenty-one orally inoculated and seven naturally infected sheep with scrapie were examined for PrPSc in peripheral tissues and in the central nervous system (CNS), using immunohistochemistry. In the inoculated group, VRQ (valine at codon 136, arginine at codon 154 and glutamine at codon 171)/VRQ sheep generally had a greater accumulation of the pathologic form of prion protein (PrPSc) in peripheral tissues, as compared with VRQ/ARQ (alanine at codon 136, arginine at codon 154, and glutamine at codon 171) animals at corresponding time points after inoculation. PrPSc was not detected in the ileal Peyer's patch, the spleen, the superficial cervical lymph node, and peripheral nervous tissues of several inoculated VRQ/ARQ animals. All inoculated VRQ/VRQ sheep, but only one of eight inoculated VRQ/ARQ animals, were PrPSc-positive in the CNS. Thus, the propagation of PrPSc seemed slower and more limited in VRQ/ARQ animals. Tissue and cellular localization of PrPSc suggested that PrPSc was disseminated through three different routes. PrPSc-positive cells in lymph node sinuses and in lymphatics indicated spreading by lymph. The sequential appearance of PrPSc in the peripheral nervous system and the CNS, with satellite cells as early targets, suggested the periaxonal transportation of PrPSc through supportive cells. Focal areas of vascular amyloid-like PrPSc in the brain of five sheep, suggested the hematogenous dissemination of PrPSc. There was a poor correlation between the amount of PrPSc in the CNS and clinical signs. One subclinically affected sheep showed widespread PrPSc accumulation in the CNS, whereas three sheep had early clinical signs without detectable PrPSc in the CNS. A VV136 (homozygous for valine at codon 136) sheep inoculated with ARQ/ARR (alanine at codon 136, arginine at codon 154, and arginine at codon 171) tissue succumbed to disease, demonstrating successful heterologous transmission. Less susceptible sheep receiving VRQ/VRQ or ARQ/ARR material were PrPSc-negative by immunohistochemistry, enzyme-linked immunosorbent assay, and western blot.

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