ABSTRACT
In recent years, studies have found that mitochondrial transfer between leukemic cells and different types of cells in their bone marrow microenvironment, especially mesenchymal stem cells, plays a key role in the occurrence, development and drug resistance of hematological malignant tumors. This paper mainly introduces the role and latest research progress of mitochondrial transfer in acute and chronic myeloid leukemia, acute lymphoblastic leukemia and multiple myeloma, and briefly describes the mechanism of drug resistance caused by mitochondrial transfer in leukemic cells during chemotherapy. The aim is to provide a new idea and theoretical basis for using intercellular mitochondrial transfer as a potential therapeutic target.
Subject(s)
Humans , Bone Marrow , Hematologic Neoplasms/metabolism , Mesenchymal Stem Cells , Mitochondria , Multiple Myeloma/metabolism , Tumor MicroenvironmentABSTRACT
Objective To explore the mechanism of human umbilical cord mesenchymal stem cell (HUC-MSC) alleviating ischemia-reperfusion injury (IRI) of liver cells through mitochondrial transfer. Methods Normal human liver cell line L02 was divided into the blank control group, oxygen-glucose deprivation (OGD) group, experimental control group, and L02 and HUC-MSC co-culture group (L02+HUC-MSC group). L02+HUC-MSC group was further divided into 10:1 co-culture subgroup (group A), 4:1 co-culture subgroup (group B), 2:1 co-culture subgroup (group C), 1:1co-culture subgroup (group D) and 1:2 co-culture subgroup (group E) according to different co-culture ratio of L02 and HUC-MSC. The apoptosis rate and relative reactive oxygen species (ROS) level of L02 cells were detected by flow cytometry. The MitoTracker positive rate of L02 cells was detected by flow cytometry. The mitochondrial transfer from HUC-MSC to L02 cells was observed by laser confocal microscope. Results The apoptosis rate and relative ROS level of L02 cells in the OGD group were significantly higher than those in the blank control group (both P < 0.05). Compared with the OGD group, the apoptosis rates of L02 cells in group B, C, D and E were significantly decreased (all P < 0.05), and the relative ROS level of L02 cells in group E was significantly declined (P < 0.05). The MitoTracker positive rate of L02 cells did not significantly differ between group A and experimental control group (P>0.05), whereas the MitoTracker positive rates of L02 cells in group B, C, D and E were significantly higher than that in the experimental control group in a concentration-dependent manner (all P < 0.05). Under the laser confocal microscope, mitochondrial transfer fromHUC-MSC to L02 cells could be observed through tunneling nanotube (TNT). Conclusions HUC-MSC may alleviate cell apoptosis and reduce ROS level of liver cells after IRI via direct mitochondrial transfer between cells.
ABSTRACT
BACKGROUND: Mesenchymal stem cells have been used in the treatment of various diseases due to their advantages, and mitochondrial transfer is an important mechanism of mesenchymal stem cell therapy. OBJECTIVE: To review the role of mesenchymal stem cells via mitochondrial transfer in various tissue injuries. METHODS: The key words were “stem cells, mitochondrial transfer, cell communication, rescue and repair, tissueinjury” in English and Chinese, respectively. PubMed, CNKI and WanFang databases were retrieved for the articles published from 2008 to 2019. The articles concerning the mitochondrial transfer function and mechanism of mesenchymal stem cells and the treatment of tissue injury were collected. After removal of the repetitive and irrelevant articles, 64 eligible articles were further analyzed. RESULTS AND CONCLUSION: Mesenchymal stem cells have been used in stroke, myocardial infarction, and acute renal failure. Mitochondrial transfer has been widely recognized as a new mechanism of stem cell therapy and has been considered as a potential therapy for tissue injuries. Mitochondrial transfer has been found to be mediated by different modes, including tunnel tube formation, gap junctions, microvesicles, cell fusion and transfer of isolated mitochondria. However, specific mechanisms of mitochondrial transfer in tissue injury have not been fully elucidated and its specific role in tissue repair also needs further investigation.
ABSTRACT
Stem cells transfer normal functional mitochondria to injured lung cells and reconstruct their function, which is one of the important mechanisms of stem cells in the treatment of lung injury. Mitochondrial translocation is mediated by intercellular gap junction (GJCs), which is unidirectional. This paper reviewed the research of stem cells for the treatment of lung injury mitochondrial transfer mechanism, to understand the clinical significance of lung mitochondria in physiological and pathological roles of mitochondria and transfer mechanisms of stem cells for the treatment of various types of lung injury.
ABSTRACT
En febrero de 2015 el Reino Unido dio el primer paso para la aprobación de la transferencia mitocondrial como técnica terapéutica. Teóricamente, gracias a eso será posible para muchas mujeres engendrar descendencia libre de patologías asociadas a defectos mitocondriales. Sin embargo, esta práctica enfrenta severas dudas desde un punto de vista ético. Entre las objeciones destacan: su estrecha vinculación con la clonación humana; la alteración de los genes de la línea germinal; la modificación de la identidad del ser humano al que dará lugar; la destrucción de embriones humanos que envuelve, o el elevado riesgo que encierra para la salud del ser humano resultante. En este texto se analiza la solvencia de todas estas objeciones de forma crítica, resaltando las fortalezas de algunas de ellas. En particular, se aboga por una restricción cuidadosa del uso de esta técnica, que promueva el empleo de alternativas más respetuosas con la salud del futuro ser humano.
In February 2015 the United Kingdom took the first step towards the adoption of mitochondrial transfer as a therapeutic technique. Theoretically, it will make it possible for many women to get rid of pathologies associated with mitochondrial defects. However, this practice has been subjected to severe doubts from an ethical standpoint. Among these objections, we could highlight the following: its close association with human cloning; the alteration of the germline genes; the modification in the identity of the human being involved; the destruction of human embryos; or the high risk to the health of the human being. In this text we will analyze these objections critically, highlighting the strength of all of them. As a result, we will call for a careful restriction of the use of this technique, and the promotion of the use of alternative options much more respectful of the human future.
Em fevereiro de 2015 o Reino Unido deu o primeiro passo para a aprovação da transferência mitocondrial como técnica terapêutica. Teoricamente, graças a isso será possível a muitas mulheres engendrar descendência livre de patologias associadas a defeitos mitocondriais. No entanto, esta prática enfrenta severas dúvidas a partir de um ponto de vista ético. Entre as objeções destacam: sua estreita vinculação com a clonagem humana; a alteração dos genes da linha germinal; a modificação da identidade do ser humano ao qual dará lugar; a destruição de embriões humanos que envolve, ou o elevado risco que encerra para a saúde do ser humano resultante. Neste texto se analisa a solvência de todas estas objeções de forma crítica, ressaltando as fortalezas de algumas delas. Em particular, se advoga por uma restrição cuidadosa do uso desta técnica, que se promova o emprego de alternativas mais respeitosas com a saúde do futuro ser humano.
Subject(s)
Humans , Cloning, Organism/ethics , Genetic Therapy/ethics , Mitochondrial Replacement Therapy/ethics , Mitochondria/transplantation , Nuclear Transfer Techniques/ethics , BioethicsABSTRACT
OBJECTIVE: This study was performed to find out mitochondrial deoxyribonucleic acid mutations in preeclampsia because Mendelian models fail to explain all the patterns of inheritance in preeclampsia. METHODS: Ten preeclampsia patients and two of their related family members who have the obstetric history of preeclampsia were studied. The mitochondrial transfer ribonucleic acidleu[UUR] gene was amplified using polymerase chain reaction, cut by a restriction endonuclease (Apa , and also sequenced to see the whole gene. RESULTS: There were neither the known mutation at Nucleotide 3243 nor other mutations on the mitochondrial transfer ribonucleic acidleu[UUR] gene in these objects. CONCLUSION: It seems that the known mutation of mitochondrial transfer ribonucleic acidleu[UUR] gene is not so frequently detected in preeclampsia of South Korean, But it could not be concluded how many South Korean women with preeclampsia have the mutation.