bims-mitrat Biomed News
on Mitochondrial transplantation and transfer
Issue of 2024–04–14
eightteen papers selected by
Gökhan Burçin Kubat, Gulhane Health Sciences Institute
  1. Potential Applications of Mitochondrial Therapy with a Focus on Parkinson's Disease and Mitochondrial Transplantation.
  2. Balbiani body of basal insects is potentially involved in multiplication and selective elimination of mitochondria.
  3. Miro GTPases at the Crossroads of Cytoskeletal Dynamics and Mitochondrial Trafficking.
  4. An Innovative Mitochondrial-targeted Gene Therapy for Cancer Treatment.
  5. The Role of Cardiolipin in Mitochondrial Function and Neurodegenerative Diseases.
  6. Mitochondria-associated endoplasmic reticulum membranes tethering protein VAPB-PTPIP51 protects against ischemic stroke through inhibiting the activation of autophagy.
  7. Right place at the right time: Mitochondrial shape, distribution and inter-organelle interaction during skeletal muscle postnatal development.
  8. Mitochondria and Reactive Oxygen Species: The Therapeutic Balance of Powers for Duchenne Muscular Dystrophy.
  9. Mitochondrial Targeted Thermosensitive Nanocarrier for Near-Infrared-Triggered Precise Synergetic Photothermal Nitric Oxide Chemotherapy.
  10. Real-time monitoring of abnormal mitochondrial viscosity in glioblastoma with a novel mitochondria-targeting fluorescent probe.
  11. Mitochondrial morphology, distribution and activity during oocyte development.
  12. Mdivi-1: Effective but complex mitochondrial fission inhibitor.
  13. Machine learning-based 3D segmentation of mitochondria in polarized epithelial cells.
  14. Effects of female bone marrow transplantation on male reproductive organs.
  15. Targeted mitochondrial fluorescence probe with large stokes shift for detecting viscosity changes in vivo and in ferroptosis process.
  16. Mesenchymal stem cell-based therapies for treating well-studied neurological disorders: a systematic review.
  17. Effects of CD34+ cell dose on engraftment and long-term outcomes after allogeneic bone marrow transplantation.
  18. Selenomethionine preconditioned mesenchymal stem cells derived extracellular vesicles exert enhanced therapeutic efficacy in intervertebral disc degeneration.
  1. Adv Pharm Bull. 2024 Mar;14(1): 147-160
    Potential Applications of Mitochondrial Therapy with a Focus on Parkinson's Disease and Mitochondrial Transplantation.
    Pranay Wal, Ankita Wal, Himangi Vig, Danish Mahmood, Mohd Masih Uzzaman Khan.
       Purpose: Both aging and neurodegenerative illnesses are thought to be influenced by mitochondrial malfunction and free radical formation. Deformities of the energy metabolism, mitochondrial genome polymorphisms, nuclear DNA genetic abnormalities associated with mitochondria, modifications of mitochondrial fusion or fission, variations in shape and size, variations in transit, modified mobility of mitochondria, transcription defects, and the emergence of misfolded proteins associated with mitochondria are all linked to Parkinson's disease.
    Methods: This review is a condensed compilation of data from research that has been published between the years of 2014 and 2022, using search engines like Google Scholar, PubMed, and Scopus.
    Results: Mitochondrial transplantation is a one-of-a-kind treatment for mitochondrial diseases and deficits in mitochondrial biogenesis. The replacement of malfunctioning mitochondria with transplanted viable mitochondria using innovative methodologies has shown promising outcomes as a cure for Parkinson's, involving tissue sparing coupled with enhanced energy generation and lower oxidative damage. Numerous mitochondria-targeted therapies, including mitochondrial gene therapy, redox therapy, and others, have been investigated for their effectiveness and potency.
    Conclusion: The development of innovative therapeutics for mitochondria-directed treatments in Parkinson's disease may be aided by optimizing mitochondrial dynamics. Many neurological diseases have been studied in animal and cellular models, and it has been found that mitochondrial maintenance can slow the death of neuronal cells. It has been hypothesized that drug therapies for neurodegenerative diseases that focus on mitochondrial dysfunction will help to delay the onset of neuronal dysfunction.
    Keywords:  Mitochondrial dynamics; Mitochondrial therapeutics; Mitochondrial transplantation; Neurodegeneration; Parkinson’s disease
    DOI:  https://doi.org/10.34172/apb.2024.019
  2. Sci Rep. 2024 04 09. 14(1): 8263
    Balbiani body of basal insects is potentially involved in multiplication and selective elimination of mitochondria.
    Malgorzata Sekula, Waclaw Tworzydlo, Szczepan M Bilinski.
      Oocytes of both vertebrates and invertebrates often contain an intricate organelle assemblage, termed the Balbiani body (Bb). It has previously been suggested that this assemblage is involved in the delivery of organelles and macromolecules to the germ plasm, formation of oocyte reserve materials, and transfer of mitochondria to the next generation. To gain further insight into the function of the Bb, we performed a series of analyses and experiments, including computer-aided 3-dimensional reconstructions, detection of DNA (mtDNA) synthesis as well as immunolocalization studies. We showed that in orthopteran Meconema meridionale, the Bb comprises a network of mitochondria and perinuclear nuage aggregations. As oogenesis progresses, the network expands filling almost entire ooplasm, then partitions into several smaller entities, termed micro-networks, and ultimately into individual mitochondria. As in somatic cells, this process involves microfilaments and elements of endoplasmic reticulum. We showed also that at least some of the individual mitochondria are surrounded by phagophores and eliminated via mitophagy. These findings support the idea that the Bb is implicated in the multiplication and selective elimination of (defective) mitochondria and therefore may participate in the transfer of undamaged (healthy) mitochondria to the next generation.
    DOI:  https://doi.org/10.1038/s41598-024-58997-6
  3. Cells. 2024 Apr 07. pii: 647. [Epub ahead of print]13(7):
    Miro GTPases at the Crossroads of Cytoskeletal Dynamics and Mitochondrial Trafficking.
    Pontus Aspenström.
      Miro GTPases are key components in the machinery responsible for transporting mitochondria and peroxisomes along microtubules, and also play important roles in regulating calcium homeostasis and organizing contact sites between mitochondria and the endoplasmic reticulum. Moreover, Miro GTPases have been shown to interact with proteins that actively regulate cytoskeletal organization and dynamics, suggesting that these GTPases participate in organizing cytoskeletal functions and organelle transport. Derailed mitochondrial transport is associated with neuropathological conditions such as Parkinson's and Alzheimer's diseases. This review explores our recent understanding of the diverse roles of Miro GTPases under cytoskeletal control, both under normal conditions and during the course of human diseases such as neuropathological disorders.
    Keywords:  Miro GTPases; Parkinson’s disease; microtubules; mitochondrial dynamics; neuropathology
    DOI:  https://doi.org/10.3390/cells13070647
  4. bioRxiv. 2024 Mar 27. pii: 2024.03.24.584499. [Epub ahead of print]
    An Innovative Mitochondrial-targeted Gene Therapy for Cancer Treatment.
    Kai Chen, Patrick Ernst, Seulhee Kim, Yingnan Si, Tanvi Varadkar, Matthew D Ringel, Xiaoguang Margaret Liu, Lufang Zhou.
      Targeting cancer cell mitochondria holds great therapeutic promise, yet current strategies to specifically and effectively destroy cancer mitochondria in vivo are limited. Here, we introduce mLumiOpto, an innovative mitochondrial-targeted luminoptogenetics gene therapy designed to directly disrupt the inner mitochondrial membrane (IMM) potential and induce cancer cell death. We synthesize a blue light-gated channelrhodopsin (CoChR) in the IMM and co-express a blue bioluminescence-emitting Nanoluciferase (NLuc) in the cytosol of the same cells. The mLumiOpto genes are selectively delivered to cancer cells in vivo by using adeno-associated virus (AAV) carrying a cancer-specific promoter or cancer-targeted monoclonal antibody-tagged exosome-associated AAV. Induction with NLuc luciferin elicits robust endogenous bioluminescence, which activates mitochondrial CoChR, triggering cancer cell IMM permeability disruption, mitochondrial damage, and subsequent cell death. Importantly, mLumiOpto demonstrates remarkable efficacy in reducing tumor burden and killing tumor cells in glioblastoma or triple-negative breast cancer xenografted mouse models. These findings establish mLumiOpto as a novel and promising therapeutic strategy by targeting cancer cell mitochondria in vivo .
    DOI:  https://doi.org/10.1101/2024.03.24.584499
  5. Cells. 2024 Mar 30. pii: 609. [Epub ahead of print]13(7):
    The Role of Cardiolipin in Mitochondrial Function and Neurodegenerative Diseases.
    José M Fuentes, Patricia Morcillo.
      Cardiolipin (CL) is a mitochondria-exclusive phospholipid synthesized in the inner mitochondrial membrane. CL plays a key role in mitochondrial membranes, impacting a plethora of functions this organelle performs. Consequently, it is conceivable that abnormalities in the CL content, composition, and level of oxidation may negatively impact mitochondrial function and dynamics, with important implications in a variety of diseases. This review concentrates on papers published in recent years, combined with basic and underexplored research in CL. We capture new findings on its biological functions in the mitochondria, as well as its association with neurodegenerative diseases such as Alzheimer's disease or Parkinson's disease. Lastly, we explore the potential applications of CL as a biomarker and pharmacological target to mitigate mitochondrial dysfunction.
    Keywords:  biological functions; cardiolipin; mitochondria; neurodegenerative diseases; therapeutic applications
    DOI:  https://doi.org/10.3390/cells13070609
  6. CNS Neurosci Ther. 2024 Apr;30(4): e14707
    Mitochondria-associated endoplasmic reticulum membranes tethering protein VAPB-PTPIP51 protects against ischemic stroke through inhibiting the activation of autophagy.
    Mingyang Li, Yonggang Zhang, Guixiang Yu, Lijuan Gu, Hua Zhu, Shi Feng, Xiaoxing Xiong, Zhihong Jian.
       AIMS: Mitochondria-associated endoplasmic reticulum membranes (MAMs) serve as a crucial bridge connecting the endoplasmic reticulum (ER) and mitochondria within cells. Vesicle-associated membrane protein-associated protein B (VAPB) and protein tyrosine phosphatase interacting protein 51 (PTPIP51) are responsible for the formation and stability of MAMs, which have been implicated in the pathogenesis of various diseases. However, the role of MAMs in ischemic stroke (IS) remains unclear. We aimed to investigate the role of MAMs tethering protein VAPB-PTPIP51 in experimental cerebral ischemia.
    METHODS: We simulated cerebral ischemia-reperfusion injury (CIRI) by using a mouse middle cerebral artery occlusion (MCAO) model.
    RESULTS: We observed a decrease in VAPB-PTPIP51 expression in the brain tissue. Our findings suggested compromised MAMs after MCAO, as a decreased mitochondria-ER contact (MERC) coverage and an increased distance were observed through the transmission electron microscope (TEM). Upon VAPB or PTPIP51 knockdown, the damage to MAMs was exacerbated, accompanied by excessive autophagy activation and increased reactive oxygen species (ROS) production, resulting in an enlarged infarct area and exacerbated neurological deficits. Notably, we observed that this damage was concomitant with the inhibition of the PI3K/AKT/mTOR pathway and was successfully mitigated by the treatment with the PI3K activator.
    CONCLUSIONS: Our findings suggest that the downregulation of VAPB-PTPIP51 expression after IS mediates structural damage to MAMs. This may exacerbate CIRI by inhibiting the PI3K pathway and activating autophagy, thus providing new therapeutic targets for IS.
    Keywords:  MAMs; PI3K/AKT/mTOR; VAPB‐PTPIP51; autophagy; ischemic stroke
    DOI:  https://doi.org/10.1111/cns.14707
  7. J Physiol. 2024 Apr 11.
    Right place at the right time: Mitochondrial shape, distribution and inter-organelle interaction during skeletal muscle postnatal development.
    Itamar C G Jesus, Marcos Eliezeck, Débora L Scheffer.
      
    Keywords:  inter‐organelle interaction; lipid droplet; mitochondria; postnatal development; skeletal muscle
    DOI:  https://doi.org/10.1113/JP286517
  8. Cells. 2024 Mar 26. pii: 574. [Epub ahead of print]13(7):
    Mitochondria and Reactive Oxygen Species: The Therapeutic Balance of Powers for Duchenne Muscular Dystrophy.
    Silvia Rosanna Casati, Davide Cervia, Paulina Roux-Biejat, Claudia Moscheni, Cristiana Perrotta, Clara De Palma.
      Duchenne muscular dystrophy (DMD) is a genetic progressive muscle-wasting disorder that leads to rapid loss of mobility and premature death. The absence of functional dystrophin in DMD patients reduces sarcolemma stiffness and increases contraction damage, triggering a cascade of events leading to muscle cell degeneration, chronic inflammation, and deposition of fibrotic and adipose tissue. Efforts in the last decade have led to the clinical approval of novel drugs for DMD that aim to restore dystrophin function. However, combination therapies able to restore dystrophin expression and target the myriad of cellular events found impaired in dystrophic muscle are desirable. Muscles are higher energy consumers susceptible to mitochondrial defects. Mitochondria generate a significant source of reactive oxygen species (ROS), and they are, in turn, sensitive to proper redox balance. In both DMD patients and animal models there is compelling evidence that mitochondrial impairments have a key role in the failure of energy homeostasis. Here, we highlighted the main aspects of mitochondrial dysfunction and oxidative stress in DMD and discussed the recent findings linked to mitochondria/ROS-targeted molecules as a therapeutic approach. In this respect, dual targeting of both mitochondria and redox homeostasis emerges as a potential clinical option in DMD.
    Keywords:  DMD therapies; Duchenne muscular dystrophy; antioxidant defense; mitochondria; mitophagy; oxidative stress; redox homeostasis; skeletal muscle
    DOI:  https://doi.org/10.3390/cells13070574
  9. ACS Appl Mater Interfaces. 2024 Apr 06.
    Mitochondrial Targeted Thermosensitive Nanocarrier for Near-Infrared-Triggered Precise Synergetic Photothermal Nitric Oxide Chemotherapy.
    Mi Wang, Mo Zhang, Jianyi Bi, Jincan Li, Xiaoxiao Hu, Lina Zhang, Yao Zhang, Wenli Wang, Yuan Lin, Hong-Bo Cheng, Jing Wang.
      Nitric oxide (NO) intervenes, that is, a potential treatment strategy, and has attracted wide attention in the field of tumor therapy. However, the therapeutic effect of NO is still poor, due to its short half-life and instability. Therapeutic concentration ranges of NO should be delivered to the target tissue sites, cell, and even subcellular organelles and to control NO generation. Mitochondria have been considered a major target in cancer therapy for their essential roles in cancer cell metabolism and apoptosis. In this study, mesoporous silicon-coated gold nanorods encapsulated with a mitochondria targeted and the thermosensitive lipid layer (AuNR@MSN-lipid-DOX) served as the carrier to load NO prodrug (BNN6) to build the near-infrared-triggered synergetic photothermal NO-chemotherapy platform (AuNR@MSN(BNN6)-lipid-DOX). The core of AuNR@MSN exhibited excellent photothermal conversion capability and high loading efficiency in terms of BNN6, reaching a high value of 220 mg/g (w/w), which achieved near-infrared-triggered precise release of NO. The outer biocompatible lipid layer, comprising thermosensitive phospholipid DPPC and mitochondrial-targeted DSPE-PEG2000-DOX, guided the whole nanoparticle to the mitochondria of 4T1 cells observed through confocal microscopy. In the mitochondria, the nanoparticles increased the local temperature over 42 °C under NIR irradiation, and a high NO concentration from BNN6 detected by the NO probe and DSPE-PEG2000-DOX significantly inhibited 4T1 cancer cells in vitro and in vivo under the synergetic photothermal therapy (PTT)-NO therapy-chemotherapy modes. The built NIR-triggered combination therapy nanoplatform can serve as a strategy for multimodal collaboration.
    Keywords:  gas therapy; gold nanorods; mesoporous silicon; mitochondria targeting; photothermal therapy; synergistic therapy
    DOI:  https://doi.org/10.1021/acsami.3c09997
  10. Analyst. 2024 Apr 10.
    Real-time monitoring of abnormal mitochondrial viscosity in glioblastoma with a novel mitochondria-targeting fluorescent probe.
    Qing Zhang, Wei Liu, Ling Jiang, Yan-Jun He, Chang-Jian Wu, Shen-Zhen Ren, Bao-Zhong Wang, Li Liu, Hai-Liang Zhu, Zhong-Chang Wang.
      Glioblastoma is the most fatal and insidious malignancy, due to the existence of the blood-brain barrier (BBB) and the high invasiveness of tumor cells. Abnormal mitochondrial viscosity has been identified as a key feature of malignancies. Therefore, this study reports on a novel fluorescent probe for mitochondrial viscosity, called ZVGQ, which is based on the twisted intramolecular charge transfer (TICT) effect. The probe uses 3-dicyanomethyl-1,5,5-trimethylcyclohexene as an electron donor moiety and molecular rotor, and triphenylphosphine (TPP) cation as an electron acceptor and mitochondrial targeting group. ZVGQ is highly selective, pH and time stable, and exhibits rapid viscosity responsiveness. In vitro experiments showed that ZVGQ could rapidly recognize to detect the changes in mitochondrial viscosity induced by nystatin and rotenone in U87MG cells and enable long-term imaging for up to 12 h in live U87MG cells. Additionally, in vitro 3D tumor spheres and in vivo orthotopic tumor-bearing models demonstrated that the probe ZVGQ exhibited exceptional tissue penetration depth and the ability to penetrate the BBB. The probe ZVGQ not only successfully visualizes abnormal mitochondrial viscosity changes, but also provides a practical and feasible tool for real-time imaging and clinical diagnosis of glioblastoma.
    DOI:  https://doi.org/10.1039/d4an00226a
  11. Trends Endocrinol Metab. 2024 Apr 09. pii: S1043-2760(24)00064-X. [Epub ahead of print]
    Mitochondrial morphology, distribution and activity during oocyte development.
    Devesh Bahety, Elvan Böke, Aida Rodríguez-Nuevo.
      Mitochondria have a crucial role in cellular function and exhibit remarkable plasticity, adjusting both their structure and activity to meet the changing energy demands of a cell. Oocytes, female germ cells that become eggs, undergo unique transformations: the extended dormancy period, followed by substantial increase in cell size and subsequent maturation involving the segregation of genetic material for the next generation, present distinct metabolic challenges necessitating varied mitochondrial adaptations. Recent findings in dormant oocytes challenged the established respiratory complex hierarchies and underscored the extent of mitochondrial plasticity in long-lived oocytes. In this review, we discuss mitochondrial adaptations observed during oocyte development across three vertebrate species (Xenopus, mouse, and human), emphasising current knowledge, acknowledging limitations, and outlining future research directions.
    Keywords:  metabolism; mitochondria; oocyte; plasticity
    DOI:  https://doi.org/10.1016/j.tem.2024.03.002
  12. Biochem Biophys Res Commun. 2024 Apr 03. pii: S0006-291X(24)00422-4. [Epub ahead of print]710 149886
    Mdivi-1: Effective but complex mitochondrial fission inhibitor.
    Seor I Ahn, Sung Kyung Choi, Myoung Jun Kim, Jinhong Wie, Jueng Soo You.
      Mdivi-1, Mitochondrial DIVIsion inhibitor 1, has been widely employed in research under the assumption that it exclusively influences mitochondrial fusion, but effects other than mitochondrial dynamics have been underinvestigated. This paper provides transcriptome and DNA methylome-wide analysis for Mdivi-1 treated SH-SY5Y human neuroblastoma cells using RNA sequencing (RNA-seq) and methyl capture sequencing (MC-seq) methods. Gene ontology analysis of RNA sequences revealed that p53 transcriptional gene network and DNA replication initiation-related genes were significantly up and down-regulated, respectively, showing the correlation with the arrest cell cycle in the G1 phase. MC-seq, a powerful sequencing method for capturing DNA methylation status in CpG sites, revealed that although Mdivi-1 does not induce dramatic DNA methylation change, the subtle alterations were concentrated within the CpG island. Integrative analysis of both sequencing data disclosed that the p53 transcriptional network was activated while the Parkinson's disease pathway was halted. Next, we investigated several changes in mitochondria in response to Mdivi-1. Copy number and transcription of mitochondrial DNA were suppressed. ROS levels increased, and elevated ROS triggered mitochondrial retrograde signaling rather than inducing direct DNA damage. In this study, we could better understand the molecular network of Mdivi-1 by analyzing DNA methylation and mRNA transcription in the nucleus and further investigating various changes in mitochondria, providing inspiration for studying nuclear-mitochondrial communications.
    Keywords:  DNA methylome; Mdivi-1; Mitochondrial dynamics; Mitochondrial retrograde signaling; Transcriptome
    DOI:  https://doi.org/10.1016/j.bbrc.2024.149886
  13. Mitochondrion. 2024 Apr 08. pii: S1567-7249(24)00040-0. [Epub ahead of print] 101882
    Machine learning-based 3D segmentation of mitochondria in polarized epithelial cells.
    Nan W Hultgren, Tianli Zhou, David S Williams.
      Mitochondria are dynamic organelles that alter their morphological characteristics in response to functional needs. Therefore, mitochondrial morphology is an important indicator of mitochondrial function and cellular health. Reliable segmentation of mitochondrial networks in microscopy images is a crucial initial step for further quantitative evaluation of their morphology. However, 3D mitochondrial segmentation, especially in cells with complex network morphology, such as in highly polarized cells, remains challenging. To improve the quality of 3D segmentation of mitochondria in super-resolution microscopy images, we took a machine learning approach, using 3D Trainable Weka, an ImageJ plugin. We demonstrated that, compared with other commonly used methods, our approach segmented mitochondrial networks effectively, with improved accuracy in different polarized epithelial cell models, including differentiated human retinal pigment epithelial (RPE) cells. Furthermore, using several tools for quantitative analysis following segmentation, we revealed mitochondrial fragmentation in bafilomycin-treated RPE cells.
    Keywords:  3D segmentation; ImageJ; Machine learning algorithm; Mitochondrial morphology; Retinal pigment epithelium
    DOI:  https://doi.org/10.1016/j.mito.2024.101882
  14. J Reprod Immunol. 2024 Apr 03. pii: S0165-0378(24)00054-8. [Epub ahead of print]163 104245
    Effects of female bone marrow transplantation on male reproductive organs.
    Tatsuhiko Takahashi, Kenta Nagahori, Takuya Omotehara, Miyuki Kuramasu, Yuki Ogawa, Xi Wu, Yutaro Natsuyama, Shinichi Kawata, Tomiko Yakura, Hidenobu Miyaso, Zhong-Lian Li, Masahiro Itoh.
      Graft-versus-host disease (GVHD), an adverse effect after bone marrow transplantation (BMT), may affect male reproductive function. It is hypothesized that a sex-mismatched BMT induces GVHD in male reproductive organs because female immune cells are not immunologically tolerant to specific antigens of the male organs. However, this hypothesis has not been experimentally verified using male (M) recipient animals following BMT from the female (F) donors. Therefore, the aim of the present study is to examine whether the female BMT to males (F→M group) induces some GVHD reactions in the testis and the other male reproductive organs. The results showed that no inflammation was found in recipients of the male BMT to males (M→M group), whereas significant inflammatory cell responses lasting for at least 4 months were induced in testis, epididymis, prostate and preputial gland in some mice of F→M group. The most severe lesion was found in the preputial gland, in which lymphocytic inflammation was accompanied by loss of glandular acini, thickening of the interstitum and increased cytokines such as TNF-α and IFN-γ. Western blot analyses revealed that sera from the F→M group reacted with various antigens of the male reproductive organs. These results indicate that transplanted female immune cells may recognize the male reproductive organs as immunologically foreign ones and induce chronic GVHD, which may affect male reproductive function.
    Keywords:  Male reproductive organs; Preputial gland; Sex-mismatched bone marrow transplantation
    DOI:  https://doi.org/10.1016/j.jri.2024.104245
  15. Spectrochim Acta A Mol Biomol Spectrosc. 2024 Apr 05. pii: S1386-1425(24)00412-8. [Epub ahead of print]315 124246
    Targeted mitochondrial fluorescence probe with large stokes shift for detecting viscosity changes in vivo and in ferroptosis process.
    Meixia Tan, Wei Li, Hongxing He, Jin Wang, Yan Chen, Yuelin Guo, Tiansheng Lin, Fang Ke.
      We created four fluorescent sensors in our work to determine the viscosity of mitochondria. Following screening, the probe Mito-3 was chosen because in contrast to the other three probes, it had a greater fluorescence enhancement, large Stokes shift (113 nm) and had a particular response to viscosity that was unaffected by polarity or biological species. As the viscosity increased from PBS to 90 % glycerol, the fluorescence intensity of probe at 586 nm increased 17-fold. Mito-3 has strong biocompatibility and is able to track changes in cell viscosity in response to nystatin and monensin stimulation. Furthermore, the probe has been successfully applied to detect changes in viscosity caused by nystatin and monensin in zebrafish. Above all, the probe can be applied to the increase in mitochondrial viscosity that accompanies the ferroptosis process. Mito-3 has the potential to help further study the relationship between viscosity and ferroptosis.
    Keywords:  Biocompatibility; Ferroptosis; Mitochondrial; Viscosity
    DOI:  https://doi.org/10.1016/j.saa.2024.124246
  16. Front Med (Lausanne). 2024 ;11 1361723
    Mesenchymal stem cell-based therapies for treating well-studied neurological disorders: a systematic review.
    Gaurav Deepak Patel, Lichao Liu, Ailian Li, Yun-Hsuan Yang, Chia-Chi Shen, Beate Brand-Saberi, Xuesong Yang.
       Background: Millions of people across the globe are affected by conditions like Amyotrophic Lateral Sclerosis (ALS), Parkinson's Disease (PD), Multiple Sclerosis (MS), Spinal Cord Injury (SCI), and Traumatic Brain Injury (TBI), although most occurrences are common in the elderly population. This systematic review aims to highlight the safety of the procedures, their tolerability, and efficacy of the available therapies conducted over the years using mesenchymal stem cells (MSCs) in treating the neurological conditions mentioned above.
    Methods: PubMed was used to search for published data from clinical trials performed using mesenchymal stem cells. Studies that provided the necessary information that mentioned the efficacy and adverse effects of the treatment in patients were considered for this review.
    Results: In total, 43 manuscripts were selected after a strategic search, and these studies have been included in this systematic review. Most included studies reported the safety of the procedures used and the treatment's good tolerability, with mild adverse events such as fever, headache, mild pain at the injection site, or nausea being common. A few studies also reported death of some patients, attributed to the progression of the disease to severe stages before the treatment. Other severe events, such as respiratory or urinary infections reported in some studies, were not related to the treatment. Different parameters were used to evaluate the efficacy of the treatment based on the clinical condition of the patient.
    Conclusion: Mesenchymal stem cells transplantation has so far proven to be safe and tolerable in select studies and patient types. This systematic review includes the results from the 43 selected studies in terms of safety and tolerability of the procedures, and several adverse events and therapeutic benefits during the follow-up period after administration of MSCs.
    Keywords:  ALS; MS; MSCs; PD; SCI; TBI; cell therapy; neurological disorders
    DOI:  https://doi.org/10.3389/fmed.2024.1361723
  17. Clin Transplant. 2024 Apr;38(4): e15313
    Effects of CD34+ cell dose on engraftment and long-term outcomes after allogeneic bone marrow transplantation.
    Takashi Oyama, Shin-Ichiro Fujiwara, Ryutaro Tominaga, Daizo Yokoyama, Atsuto Noguchi, Shuka Furuki, Shunsuke Koyama, Rui Murahashi, Hirotomo Nakashima, Kazuki Hyodo, Takashi Ikeda, Shin-Ichiro Kawaguchi, Yumiko Toda, Takashi Nagayama, Kento Umino, Daisuke Minakata, Kaoru Morita, Masahiro Ashizawa, Chihiro Yamamoto, Kaoru Hatano, Kazuya Sato, Ikuko Otsuki, Ken Ohmine, Yoshinobu Kanda.
       BACKGROUND: The number of CD34+ cells in the graft is generally associated with time to engraftment and survival in transplantation using cord blood or allogeneic peripheral blood stem cells. However, the significance of abundant CD34+ in bone marrow transplantation (BMT) remained unclear.
    METHODS: We retrospectively reviewed 207 consecutive adult patients who underwent their first BMT at Jichi Medical University between January 2009 and June 2021.
    RESULTS: The median nucleated cell count (NCC) and CD34+ cell dose were 2.17 × 108/kg (range .56-8.52) and 1.75 × 106/kg (.21-5.84), respectively. Compared with 104 patients in the low CD34+ group (below the median), 103 patients in the high CD34+ group (above the median) showed faster engraftment at day +28 in terms of neutrophil (84.6% vs. 94.2%; p =  .001), reticulocyte (51.5% vs. 79.6%; p < .001), and platelet (39.4% vs. 72.8%; p < .001). There were no significant differences in overall survival, relapse, nonrelapse mortality, acute or chronic graft-versus-host disease, or infectious complications between the two groups in univariate and multivariate analyses. Low or high NCC had no significant effect on overall survival, nonrelapse mortality, cumulative incidence of relapse and graft-versus-host disease, either. While a positive correlation was observed between NCC and the CD34+ cell dose, a high CD34+ cell dose was associated with rapid hematopoietic recovery, even in patients with NCC below the median.
    CONCLUSION: Measurement of CD34+ cell dose in addition to NCC was useful for predicting hematopoietic recovery, but seemed to have little influence on the long-term outcome in BMT.
    Keywords:  CD34+ cell dose; bone marrow transplantation; engraftment; nucleated cell count; overall survival
    DOI:  https://doi.org/10.1111/ctr.15313
  18. Int Immunopharmacol. 2024 Apr 08. pii: S1567-5769(24)00546-0. [Epub ahead of print]132 112028
    Selenomethionine preconditioned mesenchymal stem cells derived extracellular vesicles exert enhanced therapeutic efficacy in intervertebral disc degeneration.
    Shengli Ma, Rui Xue, Haiyang Zhu, Yu Han, Xiang Ji, Chaoyang Zhang, Na Wei, Jingjing Xu, Feng Li.
      Extracellular vesicles (EVs) derived from Mesenchymal Stromal Cells (MSCs) have shown promising therapeutic potential for multiple diseases, including intervertebral disc degeneration (IDD). Nevertheless, the limited production and unstable quality of EVs hindered the clinical application of EVs in IDD. Selenomethionine (Se-Met), the major form of organic selenium present in the cereal diet, showed various beneficial effects, including antioxidant, immunomodulatory and anti-apoptotic effects. In the current study, Se-Met was employed to treat MSCs to investigate whether Se-Met can facilitate the secretion of EVs by MSCs and optimize their therapeutic effects on IDD. On the one hand, Se-Met promoted the production of EVs by enhancing the autophagy activity of MSCs. On the other hand, Se-Met pretreated MSC-derived EVs (Se-EVs) exhibited an enhanced protective effects on alleviating nucleus pulposus cells (NPCs) senescence and attenuating IDD compared with EVs isolated from control MSCs (C-EVs) in vitro and in vivo. Moreover, we performed a miRNA microarray sequencing analysis on EVs to explore the potential mechanism of the protective effects of EVs. The result indicated that miR-125a-5p is markedly enriched in Se-EVs compared to C-EVs. Further in vitro and in vivo experiments revealed that knockdown of miR-125a-5p in Se-EVs (miRKD-Se-EVs) impeded the protective effects of Se-EVs, while overexpression of miR-125a-5p (miROE-Se-EVs) boosted the protective effects. In conclusion, Se-Met facilitated the MSC-derived EVs production and increased miR-125a-5p delivery in Se-EVs, thereby improving the protective effects of MSC-derived EVs on alleviating NPCs senescence and attenuating IDD.
    Keywords:  Autophagy; Extracellular vesicles; Intervertebral disc degeneration; Mesenchymal stromal cells; Selenomethionine
    DOI:  https://doi.org/10.1016/j.intimp.2024.112028
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