Recommendations for mitochondria transfer and transplantation nomenclature and characterization.

Intercellular mitochondria transfer is an evolutionarily conserved process in which one cell delivers some of their mitochondria to another cell in the absence of cell division. This process has diverse functions depending on the cell types involved and physiological or disease context. Although mitochondria transfer was first shown to provide metabolic support to acceptor cells, recent studies have revealed diverse functions of mitochondria transfer, including, but not limited to, the maintenance of mitochondria quality of the donor cell and the regulation of tissue homeostasis and remodelling.

Mitochondrial transplantation normalizes transcriptomic and proteomic shift associated with ischemia reperfusion injury in neonatal hearts donated after circulatory death.

Heart transplantation remains the ultimate treatment strategy for neonates and children with medically refractory end-stage heart failure and utilization of donors after circulatory death (DCD) can expand th donor pool. We have previously shown that mitochondrial transplantation preserves myocardial function and viability in neonatal swine DCD hearts to levels similar to that observed in donation after brain death (DBD). Herein, we sought to investigate the transcriptomic and proteomic pathways implicated in these phenotypic changes using ex situ perfused swine hearts.

Xenotransplantation of mitochondria: A novel strategy to alleviate ischemia-reperfusion injury during ex vivo lung perfusion.

Background: Ischemia-reperfusion injury (IRI) plays a crucial role in the development of primary graft dysfunction (PGD) following lung transplantation. A promising novel approach to optimize donor organs before transplantation and reduce the incidence of PGD is mitochondrial transplantation.

Methods: In this study, we explored the delivery of isolated mitochondria in 4 hours ex vivo lung perfusion (EVLP) before transplantation as a means to mitigate IRI.

Mitochondria Transplantation: Rescuing Innate Muscle Bioenergetic Impairment in a Model of Aging and Exercise Intolerance.

Arroum, T, Hish, GA, Burghardt, KJ, Ghamloush, M, Bazzi, B, Mrech, A, Morse, PT, Britton, SL, Koch, LG, McCully, JD, Hüttemann, M, and Malek, MH. Mitochondria transplantation: Rescuing innate muscle bioenergetic impairment in a model of aging and exercise intolerance. J Strength Cond Res 38(7): 1189-1199, 2024-Mitochondria, through oxidative phosphorylation, are crucial for energy production.

Bridging the gap between in vitro and in vivo models: a way forward to clinical translation of mitochondrial transplantation in acute disease states.

Mitochondrial transplantation and transfer are being explored as therapeutic options in acute and chronic diseases to restore cellular function in injured tissues. To limit potential immune responses and rejection of donor mitochondria, current clinical applications have focused on delivery of autologous mitochondria. We recently convened a Mitochondrial Transplant Convergent Working Group (CWG), to explore three key issues that limit clinical translation: (1) storage of mitochondria, (2) biomaterials to enhance mitochondrial uptake, and (3) dynamic models to mimic the complex recipient tissue environment.

Using the gli spirographic prediction equations to revisit the allometric relationships between lung volumes, height and age in adults.

The determination the forced vital capacity (FVC) and the forced expiratory volume in 1 second (FEV1) during spirometry studies, is at the core of the evaluation of the pulmonary function of patients with respiratory diseases. The Global Lung Function Initiative (GLI) offers the most extensive data set of normal lung functions available, which is currently used to determine the average expected/predicted FEV1 and FVC (V), and their lower limit of normal (LLN, 5th percentile) at any given height and age for women and men. These prediction equations are currently expressed in a rather complex form: V = exp [p+ (a x Ln (height) + (n x Ln (age)) + spline] and LLN = exp(Ln (V) + Ln (1 - 1.

Model of Ischemia and Reperfusion Injury in Rabbits.

The protocol here provides a simple, highly replicable methodology to induce in situ acute regional myocardial ischemia in the rabbit for non-survival and survival experiments. New Zealand White adult rabbit is sedated with atropine, acepromazine, butorphanol, and isoflurane. The animal is intubated and placed on mechanical ventilation.

Oestradiol concentrations in trans women with HIV suppressed on unboosted integrase inhibitor regimens versus trans women without HIV taking oral oestradiol: a pilot study.

Background: Feminizing hormone therapy (FHT) is essential to many trans women. Concern about negative drug interactions between FHT and ART can be an ART adherence barrier among trans women with HIV.

Objectives: In this single-centre, parallel group, cross-sectional pilot study, we measured serum oestradiol concentrations in trans women with HIV taking FHT and unboosted integrase strand transfer inhibitor (INSTI)-based ART versus trans women without HIV taking FHT.

Mitochondria Transplantation Mitigates Damage in an In Vitro Model of Renal Tubular Injury and in an Ex Vivo Model of DCD Renal Transplantation.

Objectives: To test whether mitochondrial transplantation (MITO) mitigates damage in 2 models of acute kidney injury (AKI).

Background: MITO is a process where exogenous isolated mitochondria are taken up by cells. As virtually any morbid clinical condition is characterized by mitochondrial distress, MITO may find a role as a treatment modality in numerous clinical scenarios including AKI.

Mitochondrial transplantation preserves myocardial function and viability in pediatric and neonatal pig hearts donated after circulatory death.

Objective: Mitochondrial transplantation has been shown to preserve myocardial function and viability in adult porcine hearts donated after circulatory death (DCD) . Herein, we investigate the efficacy of mitochondrial transplantation for the preservation of myocardial function and viability in neonatal and pediatric porcine DCD heart donation.

Methods: Circulatory death was induced in neonatal and pediatric Yorkshire pigs by cessation of mechanical ventilation.

Mitochondrial transplantation: Effects on chemotherapy in prostate and ovarian cancer cells in vitro and in vivo.

Prostate and ovarian cancers affect the male and female reproductive organs and are among the most common cancers in developing countries. Previous studies have demonstrated that cancer cells have a high rate of aerobic glycolysis that is present in nearly all invasive human cancers and persists even under normoxic conditions. Aerobic glycolysis has been correlated with chemotherapeutic resistance and tumor aggressiveness.

Transcriptomic and proteomic pathways of diabetic and non-diabetic mitochondrial transplantation.

Reduced mitochondrial function increases myocardial susceptibility to ischemia-reperfusion injury (IRI) in diabetic hearts. Mitochondrial transplantation (MT) ameliorates IRI, however, the cardioprotective effects of MT may be limited using diabetic mitochondria. Zucker Diabetic Fatty (ZDF) rats were subjected to temporary myocardial RI and then received either vehicle alone or vehicle containing mitochondria isolated from either diabetic ZDF or non-diabetic Zucker lean (ZL) rats.

Mitochondrial remodeling and ischemic protection by G protein-coupled receptor 35 agonists.

Kynurenic acid (KynA) is tissue protective in cardiac, cerebral, renal, and retinal ischemia models, but the mechanism is unknown. KynA can bind to multiple receptors, including the aryl hydrocarbon receptor, the a7 nicotinic acetylcholine receptor (a7nAChR), multiple ionotropic glutamate receptors, and the orphan G protein-coupled receptor GPR35. Here, we show that GPR35 activation was necessary and sufficient for ischemic protection by KynA.

Mitochondrial transplantation for organ rescue.

Mitochondrial transplantation involves the replacement or augmentation of native mitochondria damaged, by ischemia, with viable, respiration-competent mitochondria isolated from non-ischemic tissue obtained from the patient's own body. The uptake and cellular functional integration of the transplanted mitochondria appears to occur in all cell types. Efficacy and safety have been demonstrated in cell culture, isolated perfused organ, in vivo large animal studies and in a first-human clinical study.

Mitochondrial Transplantation for Ischemia Reperfusion Injury.

Mitochondrial transplantation is a novel therapeutic intervention to treat ischemia-reperfusion-related disorders. This approach uses replacement of native mitochondria with viable, respiration-competent mitochondria isolated from non-ischemic tissue obtained from the patient's own body, to overcome the many deleterious effects of ischemia-reperfusion injury on native mitochondria. The safety and efficacy of this methodology has been demonstrated in cell culture, animal models and has been shown to be safe and efficacious in a phase I clinical trial in pediatric cardiac patients with ischemia-reperfusion injury.

A Large Animal Model for Acute Kidney Injury by Temporary Bilateral Renal Artery Occlusion.

Acute kidney injury (AKI) is associated with higher risk for morbidity and mortality post-operatively. Ischemia-reperfusion injury (IRI) is the most common cause of AKI. To mimic this clinical scenario, this study presents a highly reproducible large animal model of renal IRI in swine using temporary percutaneous bilateral balloon-catheter occlusion of the renal arteries.

Autologous mitochondrial transplantation for cardiogenic shock in pediatric patients following ischemia-reperfusion injury.

Objectives: To report outcomes in a pilot study of autologous mitochondrial transplantation (MT) in pediatric patients requiring postcardiotomy extracorporeal membrane oxygenation (ECMO) for severe refractory cardiogenic shock after ischemia-reperfusion injury (IRI).

Methods: A single-center retrospective study of patients requiring ECMO for postcardiotomy cardiogenic shock following IRI between May 2002 and December 2018 was performed. Postcardiotomy IRI was defined as coronary artery compromise followed by successful revascularization.

A Multi-Mode System for Myocardial Functional and Physiological Assessment during Ex Situ Heart Perfusion.

Ex situ heart perfusion (ESHP) has proven to be an important and valuable step toward better preservation of donor hearts for heart transplantation. Currently, few ESHP systems allow for a convenient functional and physiological evaluation of the heart. We sought to establish a simple system that provides functional and physiological assessment of the heart during ESHP.

Autogenous mitochondria transplantation for treatment of right heart failure.

Background: Right ventricular hypertrophy and failure are major causes of cardiac morbidity and mortality. A key event in the progression to right ventricular hypertrophy and failure is cardiomyocyte apoptosis due to mitochondrial dysfunction. We sought to determine whether localized intramyocardial injection of autologous mitochondria from healthy muscle treats heart failure.