The homing of human cord blood stem cells to sites of inflammation

Velpula, Kiran Kumar; Dasari, Venkata Ramesh; Rao, Jasti S.

doi:10.4161/cc.20766

Cited by 11 publications

(3 citation statements)

References 46 publications

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“…MSCs are particularly prone to engage in TNT connections and mitochondria donation to different cell types, including cardiomyocytes [29,59,89], lung epithelial cells [31,35,36], renal tubular cells [60], vascular smooth muscle cells [69], corneal epithelial cells [32] and macrophages [49] (Table 1). Apart from their role in tissue homeostasis, MSCs are also known to be recruited to tumors [90,91]. TNT-mediated mitochondria transfer was actually observed between MSCs and different cancer cells, including breast and ovarian cancers, melanoma, acute myeloid leukemia as well as glioblastoma as shown in Figure 1 [52][53][54][55].…”

Section: Mechanisms Of Intercellular Mitochondria Transfermentioning

confidence: 93%

Intercellular mitochondria trafficking highlighting the dual role of mesenchymal stem cells as both sensors and rescuers of tissue injury

et al. 2018

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Mitochondria are crucial organelles that not only regulate the energy metabolism, but also the survival and fate of eukaryotic cells. Mitochondria were recently discovered to be able to translocate from one cell to the other. This phenomenon was observed in vitro and in vivo, both in physiological and pathophysiological conditions including tissue injury and cancer. Mitochondria trafficking was found to exert prominent biological functions. In particular, several studies pointed out that this process governs some of the therapeutic effects of mesenchymal stem cells (MSCs). In this review, we give an overview of the current knowledge on MSC-dependent intercellular mitochondria trafficking and further discuss the recent findings on the intercellular mitochondria transfer between differentiated and mesenchymal stem cells, their biological significance and the mechanisms underlying this process.

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Section: Mechanisms Of Intercellular Mitochondria Transfermentioning

confidence: 93%

Intercellular mitochondria trafficking highlighting the dual role of mesenchymal stem cells as both sensors and rescuers of tissue injury

et al. 2018

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“…In particular, mitochondria transfer from MSCs has been reported as one of the means allowing cancer cells to escape therapy. Consistently, the presence of MSCs in GBM tumors is associated with a poor prognosis ( 39, 40, 42, 43 ). However, the biological mechanisms for this chemotherapy resistance have not been determined so far.…”

Section: Discussionmentioning

confidence: 83%

Mitochondria Transfer from Mesenchymal Stem Cells Confers Chemoresistance to Glioblastoma Stem Cells through Metabolic Rewiring

Nakhle

Khattar

Özkan

et al. 2023

Cancer Research Communications

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Glioblastomas (GBM) are heterogeneous tumors with high metabolic plasticity. Their poor prognosis is linked to the presence of glioblastoma stem cells (GSCs), which support resistance to therapy, notably to temozolomide (TMZ). Mesenchymal stem cells (MSCs) recruitment to GBM contributes to GSC chemoresistance, by mechanisms still poorly understood. Here, we provide evidence that MSCs transfer mitochondria to GSCs through tunneling nanotubes, which enhances GSCs resistance to TMZ. More precisely, our metabolomics analyses reveal that MSC mitochondria induce GSCs metabolic reprograming, with a nutrient shift from glucose to glutamine, a rewiring of the TCA cycle from glutaminolysis to reductive carboxylation and increase in orotate turnover as well as in pyrimidine and purine synthesis. Metabolomics analysis of GBM patient tissues at relapse after TMZ treatment documents increased concentrations of AMP, CMP, GMP and UMP nucleotides and thus corroborate our in vitro analyses. Finally, we provide a mechanism whereby mitochondrial transfer from MSCs to GSCs contributes to GBM resistance to TMZ therapy, by demonstrating that inhibition of orotate production by Brequinar (BRQ) restores TMZ sensitivity in GSCs with acquired mitochondria. Altogether, these results identify a mechanism for GBM resistance to TMZ and reveal a metabolic dependency of chemoresistant GBM following the acquisition of exogenous mitochondria, which opens therapeutic perspectives based on synthetic lethality between TMZ and BRQ.

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“…Moreover, GRO have been demonstrated to be crucial in the mobilization and homing of stem cells [38,39,40]. During in vitro expansion, MSCs constitutively secrete GRO chemokines [35,41,42], which in turn regulate the biological behaviors of MSCs through binding to their cell-surface cognate receptor, CXCR2 [22,36,37]. Besides, GRO production from MSCs can be significantly increased by the stimulation of IL-1β and TNF-α [15,18,41].…”

Section: Discussionmentioning

confidence: 99%

Inflammatory Microenvironment Changes the Secretory Profile of Mesenchymal Stem Cells to Recruit Mesenchymal Stem Cells

Xing

Hou

Jin

et al. 2014

Cell Physiol Biochem

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Background/Aims: Human bone-marrow mesenchymal stem cells (hBMSCs) are widely transplanted into inflammatory microenvironment to accelerate tissue regeneration. Transplanted hBMSCs recruit host hBMSCs through a poorly understood mechanism. This study was aimed to determine whether and how inflammatory microenvironment influenced the host-hBMSCs-recruiting capability of transplanted hBMSCs. Methods: Pro-inflammatory factors, including IL-1β, IL-6 and TNF-α, were utilized to mimic inflammatory microenvironment. hBMSCs were cultured and conditioned media (CM) were collected. The effects of inflammatory microenvironment on the host-hBMSCs-recruiting capability of cultured hBMSCs were revealed by transwell migration assays. Employing semi-quantitative and quantitative cytokine antibody assays, we examined the secretory profile of cultured hBMSCs. Results: CM from cultured hBMSCs exerted excellent host-hBMSCs-recruiting capability, which was significantly promoted by exposure to inflammatory microenvironment. Within inflammatory microenvironment, hBMSCs secreted more chemokines related to cell migration. Finally, 21 cytokines were verified as potential factors accounting for the enhanced host-hBMSCs-recruiting capability of cultured hBMSCs exposed to inflammatory microenvironment. Conclusion: These results strongly suggested that in clinic, inflammatory microenvironment might promote the host-hBMSCs-recruiting capacity of transplanted hBMSCs by increasing chemokines secretion. Modulation of such characteristics of hBMSCs might provide novel therapeutic ideas in the context of hBMSCs.

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The homing of human cord blood stem cells to sites of inflammation

Cited by 11 publications

References 46 publications

Intercellular mitochondria trafficking highlighting the dual role of mesenchymal stem cells as both sensors and rescuers of tissue injury

Intercellular mitochondria trafficking highlighting the dual role of mesenchymal stem cells as both sensors and rescuers of tissue injury

Mitochondria Transfer from Mesenchymal Stem Cells Confers Chemoresistance to Glioblastoma Stem Cells through Metabolic Rewiring

Inflammatory Microenvironment Changes the Secretory Profile of Mesenchymal Stem Cells to Recruit Mesenchymal Stem Cells

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