scholarly journals Artificial Mitochondria Transfer: Current Challenges, Advances, and Future Applications

2017 ◽  
Vol 2017 ◽  
pp. 1-23 ◽  
Author(s):  
Andrés Caicedo ◽  
Pedro M. Aponte ◽  
Francisco Cabrera ◽  
Carmen Hidalgo ◽  
Maroun Khoury
Keyword(s):  
Power Plants ◽  
Ethical Issues ◽  
Transport Processes ◽  
Optimum Quantity ◽  
Cell Tissue ◽  
Mitochondrial Transfer ◽  
Mitochondria Transfer ◽  
Key Questions

The objective of this review is to outline existing artificial mitochondria transfer techniques and to describe the future steps necessary to develop new therapeutic applications in medicine. Inspired by the symbiotic origin of mitochondria and by the cell’s capacity to transfer these organelles to damaged neighbors, many researchers have developed procedures to artificially transfer mitochondria from one cell to another. The techniques currently in use today range from simple coincubations of isolated mitochondria and recipient cells to the use of physical approaches to induce integration. These methods mimic natural mitochondria transfer. In order to use mitochondrial transfer in medicine, we must answer key questions about how to replicate aspects of natural transport processes to improve current artificial transfer methods. Another priority is to determine the optimum quantity and cell/tissue source of the mitochondria in order to induce cell reprogramming or tissue repair, in both in vitro and in vivo applications. Additionally, it is important that the field explores how artificial mitochondria transfer techniques can be used to treat different diseases and how to navigate the ethical issues in such procedures. Without a doubt, mitochondria are more than mere cell power plants, as we continue to discover their potential to be used in medicine.

TAMI-51. HORIZONTAL MITOCHONDRIAL TRANSFER FROM THE TUMOR MICROENVIRONMENT TO GLIOBLASTOMA INCREASES TUMORIGENICITY

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi208-vi209
Author(s):  
Dionysios Watson ◽  
Defne Bayik ◽  
Justin Lathia
Keyword(s):  
Bone Marrow ◽  
Tumor Microenvironment ◽  
Tumor Cells ◽  
Bone Marrow Cells ◽  
Treatment Strategies ◽  
Tumor Initiating Cells ◽  
Mitochondrial Transfer ◽  
Mitochondria Transfer

Abstract Communication between glioblastoma (GBM) and its microenvironment facilitates tumor growth and therapeutic resistance, and is facilitated through a variety of mechanisms. Organelle transfer between cells was recently observed, including mitochondria transfer from astrocytes to neurons after ischemic stroke. Given the dependence of GBM on microenvironmental interactions, we hypothesized that mitochondria transfer from tumor microenvironment to GBM cells could occur and affect metabolism and tumorigenicity. We interrogated this in vivo by establishing intracranial GBM tumors in mito::mKate2 mice (with trackable fluorescent mitochondria) using syngeneic GFP-expressing tumor cells (SB28 and GL261 models). We also cultured stromal cell types from mito::mKate2 mice with tumor cells, enabling sorting of tumor cells with and without exogenous mitochondria. Confocal microscopy revealed horizontal transfer of mKate2+ mitochondria from mouse cells to implanted GBM cells in vivo and was confirmed by flow cytometry where 20-40% of GBM cells acquired exogenous mitochondria. Transfer was negligible in wildtype mice transplanted with mito::mKate2 bone marrow cells, suggesting that brain-resident cells were the main donors. In vitro, astrocytes and microglia exhibited 5 to 10-fold higher mitochondrial transfer rate than bone-marrow derived macrophages. Seahorse metabolic profiling revealed that GBM cells with mKate2+ mitochondria had 40% lower respiratory reserve compared to cells without exogenous mitochondria. Median survival of mice implanted with SB28 that acquired mitochondria was significantly shorter and in vivo limiting dilution confirmed the frequency of tumor-initiating cells was 3-fold higher in SB28 cells with exogenous mitochondria. Our data indicate that horizontal mitochondrial transfer from brain-resident glia to mouse GBM tumors alters tumor cell metabolism and increases their tumorigenicity. Ongoing studies are assessing gene expression in GBM cells acquiring exogenous mitochondria; validating findings in human specimens; and screening for transfer inhibitor drugs. Horizontal mitochondrial transfer represents a foundational tumor microenvironment interaction contributing to glioblastoma plasticity, and is likely to inform next-generation treatment strategies.

scholarly journals Protective mitochondrial transfer from bone marrow stromal cells to acute myeloid leukemic cells during chemotherapy

Blood ◽  
2016 ◽  
Vol 128 (2) ◽  
pp. 253-264 ◽  
Author(s):  
Ruxanda Moschoi ◽  
Véronique Imbert ◽  
Marielle Nebout ◽  
Johanna Chiche ◽  
Didier Mary ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Leukemic Cells ◽  
Mitochondrial Transfer ◽  
Key Points ◽  
Mitochondria Transfer ◽  
Endocytic Pathways

Key Points Bone marrow mesenchymal stromal cells transfer functional mitochondria to AML cells in vitro and in vivo through endocytic pathways. This mitochondria transfer is enhanced by some chemotherapies and confers a survival advantage to leukemic blasts and leukemia initiating cells.

scholarly journals Tobacco Mosaic Virus Movement Protein Functions as a Structural Microtubule-Associated Protein

2006 ◽  
Vol 80 (17) ◽  
pp. 8329-8344 ◽  
Author(s):  
Jamie Ashby ◽  
Emmanuel Boutant ◽  
Mark Seemanpillai ◽  
Adrian Sambade ◽  
Christophe Ritzenthaler ◽  
...  
Keyword(s):  
Tobacco Mosaic Virus ◽  
Mosaic Virus ◽  
Movement Protein ◽  
Cell Extract ◽  
Transport Processes ◽  
In Vitro Assays ◽  
Protein Functions ◽  
Intercellular Spread

ABSTRACT The cell-to-cell spread of Tobacco mosaic virus infection depends on virus-encoded movement protein (MP), which is believed to form a ribonucleoprotein complex with viral RNA (vRNA) and to participate in the intercellular spread of infectious particles through plasmodesmata. Previous studies in our laboratory have provided evidence that the vRNA movement process is correlated with the ability of the MP to interact with microtubules, although the exact role of this interaction during infection is not known. Here, we have used a variety of in vivo and in vitro assays to determine that the MP functions as a genuine microtubule-associated protein that binds microtubules directly and modulates microtubule stability. We demonstrate that, unlike MP in whole-cell extract, microtubule-associated MP is not ubiquitinated, which strongly argues against the hypothesis that microtubules target the MP for degradation. In addition, we found that MP interferes with kinesin motor activity in vitro, suggesting that microtubule-associated MP may interfere with kinesin-driven transport processes during infection.

scholarly journals Bone marrow regeneration requires mitochondrial transfer from donor Cx43-expressing hematopoietic progenitors to stroma

Blood ◽  
2020 ◽  
Vol 136 (23) ◽  
pp. 2607-2619 ◽  
Author(s):  
Karin Golan ◽  
Abhishek K. Singh ◽  
Orit Kollet ◽  
Mayla Bertagna ◽  
Mark J. Althoff ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Connexin 43 ◽  
Purinergic Receptor ◽  
Cell Contact ◽  
Hematopoietic Stem ◽  
Mitochondrial Transfer ◽  
Stem And Progenitor Cells ◽  
Mitochondria Transfer ◽  
Bone Marrow Regeneration

Abstract The fate of hematopoietic stem and progenitor cells (HSPC) is tightly regulated by their bone marrow (BM) microenvironment (ME). BM transplantation (BMT) frequently requires irradiation preconditioning to ablate endogenous hematopoietic cells. Whether the stromal ME is damaged and how it recovers after irradiation is unknown. We report that BM mesenchymal stromal cells (MSC) undergo massive damage to their mitochondrial function after irradiation. Donor healthy HSPC transfer functional mitochondria to the stromal ME, thus improving mitochondria activity in recipient MSC. Mitochondrial transfer to MSC is cell-contact dependent and mediated by HSPC connexin-43 (Cx43). Hematopoietic Cx43-deficient chimeric mice show reduced mitochondria transfer, which was rescued upon re-expression of Cx43 in HSPC or culture with isolated mitochondria from Cx43 deficient HSPCs. Increased intracellular adenosine triphosphate levels activate the purinergic receptor P2RX7 and lead to reduced activity of adenosine 5′-monophosphate–activated protein kinase (AMPK) in HSPC, dramatically increasing mitochondria transfer to BM MSC. Host stromal ME recovery and donor HSPC engraftment were augmented after mitochondria transfer. Deficiency of Cx43 delayed mesenchymal and osteogenic regeneration while in vivo AMPK inhibition increased stromal recovery. As a consequence, the hematopoietic compartment reconstitution was improved because of the recovery of the supportive stromal ME. Our findings demonstrate that healthy donor HSPC not only reconstitute the hematopoietic system after transplantation, but also support and induce the metabolic recovery of their irradiated, damaged ME via mitochondria transfer. Understanding the mechanisms regulating stromal recovery after myeloablative stress are of high clinical interest to optimize BMT procedures and underscore the importance of accessory, non-HSC to accelerate hematopoietic engraftment.

Ligand-displacement-based two-photon fluorogenic probe for visualizing mercapto biomolecules in live cells, Drosophila brains and zebrafish

The Analyst ◽  
2018 ◽  
Vol 143 (14) ◽  
pp. 3433-3441 ◽  
Author(s):  
Yanfei Zhao ◽  
Yun Ni ◽  
Liulin Wang ◽  
Chenchen Xu ◽  
Chenqi Xin ◽  
...  
Keyword(s):  
Rapid Detection ◽  
Live Cell ◽  
Live Cells ◽  
Two Photon ◽  
Ligand Displacement ◽  
Cell Tissue ◽  
Fluorogenic Probe ◽  
Displacement Based

We report the Fe(iii)-based complex TPFeS which acts as a novel ligand-displacement-based TP fluorogenic probe for the rapid detection of mercapto biomolecules both in vitro and in live cell/tissue/in vivo imaging.

P315In-vivo and vitro mitochondrial transfer from adipose-derived mesenchymal stem cell to ischemic cardiomyocyte

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
D Mori ◽  
S Miyagawa ◽  
T Kawamura ◽  
H Hata ◽  
T Ueno ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Functional Recovery ◽  
Pcr Analysis ◽  
Sham Operation ◽  
Rat Cardiomyocytes ◽  
Mitochondrial Transfer ◽  
Group A

Abstract Background Although transplantation of human Adipose-derived Mesenchymal stem cell (hADSC) shows efficacy in the treatment of ischemic cardiomyopathy, its therapeutic mechanisms have not been fully elucidated. It has been already reported that mitochondria transfer to recipient cells have impact on resistance to injury and tissue regeneration, however this phenomenon has not been elucidated in the damaged heart. Therefore, we hypothesized that ADSC transfer own mitochondria to cardiomyocytes in-vivo and in-vitro under ischemic condition, resulting in the functional recovery of cardiomyocyte. Method and result Transplantation of hADSC (group A) to the heart surface or sham operation (group C) was performed in rats that were subjected to LAD ligation 2 weeks prior to the treatment (n=10 each). The number of transplant cell was 1x106/body. Three days after transplantation, transferred hADSCs' mitochondria were observed in recipient cardiomyocytes histologically (Figure). Quantitative PCR analysis revealed that mitochondrial genome of recipient myocytes increased over time. The cardiac function assessed with echocardiography was significantly better in group A. Furthermore, live-imaging of hADSC transplantation revealed the suspected transfer of mitochondria to beating heart. In-vitro, the co-culture of rat cardiomyocytes (rCM) and hADSC was observed with time-lapse photography and demonstrated mitochondrial transfer under the hypoxic condition. The measuring the oxygen consumption rate (OCR) of these cells showed that OCR of rCM was reinforced by co-culture with hADSC conspicuously. Figure 1 Conclusion Mitochondrial transfer from hADSC to rCM was suggested in-vivo and in-vitro ischemic condition and suspected to be related to functional recovery of ischemic cardiomyocyte.

Human duodenal mucosal brush border Na+/H+ exchangers NHE2 and NHE3 alter net bicarbonate movement

2001 ◽  
Vol 281 (1) ◽  
pp. G159-G163 ◽  
Author(s):  
Maltin Repishti ◽  
Daniel L. Hogan ◽  
Vijaya Pratha ◽  
Laura Davydova ◽  
Mark Donowitz ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Brush Border ◽  
Polyclonal Antibodies ◽  
Duodenal Mucosa ◽  
Transport Processes ◽  
Apical Surface ◽  
Luminal Perfusion ◽  
Significant Step

The proximal duodenal mucosa secretes HCO[Formula: see text] that serves to protect the epithelium from injury. In isolated human duodenal enterocytes in vitro, multiple luminal membrane proteins are involved in acid/base transport. We postulated that one or more isoforms of the Na+/H+ exchanger (NHE) family is located on the apical surface of human duodenal mucosal epithelial cells and thereby contributes to duodenal mucosal HCO[Formula: see text] transport. Duodenal biopsies were obtained from human volunteers, and the presence of NHE2 and NHE3 was determined by using previously characterized polyclonal antibodies (Ab 597 for NHE2 and Ab 1381 for NHE3). In addition, proximal duodenal mucosal HCO[Formula: see text] transport was measured in humans in vivo in response to luminal perfusion of graded doses of amiloride; 10−5–10−4 M amiloride was used to inhibit NHE2 and 10−3 M amiloride to inhibit NHE3. Both NHE2 and NHE3 were localized principally to the brush border of duodenal villus cells. Sequential doses of amiloride resulted in significant, step-wise increases in net duodenal HCO[Formula: see text] output. Inhibition of NHE2 with 10−5 M and 10−4 M amiloride significantly increased net HCO[Formula: see text] output. Moreover, there was an additional, equivalent increase ( P < 0.05) in duodenal HCO[Formula: see text] output with 10−3 M amiloride, which inhibited NHE3. We conclude that 1) NHE2 and NHE3 are localized principally to the brush border of human duodenal villus epithelial cells; 2) sequential inhibition of NHE2 and NHE3 isoforms resulted in step-wise increases in net HCO[Formula: see text]output; 3) NHE2 and NHE3 participate in human duodenal villus cell HCO[Formula: see text] transport; and 4) the contribution of NHE-related transport events should be considered when studying duodenal HCO[Formula: see text] transport processes.

scholarly journals Teaching and training in substitutive approaches to animal testing: Commitment of the University of Genoa

2020 ◽  
Author(s):  
Anna Maria Bassi
Keyword(s):  
Work Experience ◽  
Ethical Issues ◽  
Animal Testing ◽  
Vitro Model ◽  
Teaching Programs ◽  
The University ◽  
Graduating Students ◽  
And Training

The 21st century life science requires that scientists become aware of scientific and ethical issues of substitutive approaches to animal testing. For more than 20 years Dr Bassi Team at University of Genoa promotes several activities in Academia on the Replacement of Animal Testing: 2 days training course, lectures within teaching programs, work experience opportunities for graduated or graduating students, stages for Biology, Medicine and Surgery degrees and PhD courses on human in vitro model disease projects, This effort is now improved by Centro3R activities to increase the number of scientists aware of effective alternatives to classical in vivo approaches, and prevent needless suffering of animals.

Cell Migration Ability Test for Bioactive Ceramics toward International Standardization of Ceramics for Regenerative Medicine

2011 ◽  
Vol 493-494 ◽  
pp. 836-839
Author(s):  
Masanori Kikuchi
Keyword(s):  
Cell Migration ◽  
Test Method ◽  
Migration Ability ◽  
Ability Test ◽  
Bioactive Ceramics ◽  
Cell Tissue ◽  
Mg63 Cells ◽  
Tissue Migration

International standard for test method on cell migration into a scaffold is one of the important things to evaluate the scaffold. The "cell migration" ability can divide into two parts. One is infiltration of cell suspension before in vitro cell culture on the scaffold. Another is migration of adherent cells from the edge of scaffold. The latter one could be closely related to cell/tissue migration into the scaffold when it is implanted into bone. Thus, in the present study, the cell migration ability was evaluated toward standardization of in vitro evaluation method for in vivo cell/tissue migration ability using several bioactive ceramics and composites including commercially available materials. The specimen 5 mm in diameter was placed on confluent MG63 cell layer. After 3 days incubation, the specimen was harvested, fixed and divided into two parts. Inside and outside of the scaffold were stained by Giemsa and observed by optical microscopy. In addition, the same specimen was critical point dried and observed with scanning electron microscope (SEM). From microscopic observation, MG63 cells migrated to pore walls of the specimen as well as a sidewall. Maximum migration distances were different among specimens and seemed to depend on pore structure and size as well as porosity. Similar behaviors were observed with SEM.Even relations between this test method and in vivo cell/tissue migration have not been evaluated, this test method is potentially a good method for testing cell migration ability of porous bioactive ceramics as well as other porous scaffold materials.

Organotypic slice cultures from rat brain tissue: a new approach forNaegleria fowleriCNS infectionin vitro

Parasitology ◽  
2005 ◽  
Vol 132 (6) ◽  
pp. 797-804 ◽  
Author(s):  
C. GIANINAZZI ◽  
M. SCHILD ◽  
N. MÜLLER ◽  
S. L. LEIB ◽  
F. SIMON ◽  
...  
Keyword(s):  
Animal Models ◽  
Rat Brain ◽  
Time Course ◽  
Ethical Issues ◽  
Brain Morphology ◽  
Specific Morphology ◽  
Organ Specific ◽  
Organotypic Slice Cultures

The free-living amoebaNaegleria fowleriis the aetiological agent of primary amoebic meningoencephalitis (PAM), a disease leading to death in the vast majority of cases. In patients suffering from PAM, and in corresponding animal models, the brain undergoes a massive inflammatory response, followed by haemorrhage and severe tissue necrosis. Both,in vivoandin vitromodels are currently being used to study PAM infection. However, animal models may pose ethical issues, are dependent upon availability of specific infrastructural facilities, and are time-consuming and costly. Conversely, cell cultures lack the complex organ-specific morphology foundin vivo, and thus, findings obtainedin vitrodo not necessarily reflect the situationin vivo. The present study reports infection of organotypic slice cultures from rat brain withN. fowleriand compares the findings in this culture system within vivoinfection in a rat model of PAM, that proved complementary to that of mice. We found that brain morphology, as presentin vivo, is well retained in organotypic slice cultures, and that infection time-course including tissue damage parallels the observationsin vivoin the rat. Therefore, organotypic slice cultures from rat brain offer a newin vitroapproach to studyN. fowleriinfection in the context of PAM.

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