Autologous non-invasively derived stem cells mitochondria transfer shows therapeutic advantages in human embryo quality rescue.

BACKGROUND: The decline in the quantity and quality of mitochondria are closely associated with infertility, particularly in advanced maternal age. Transferring autologous mitochondria into the oocytes of infertile females represents an innovative and viable strategy for treating infertility, with no concerns regarding ethical considerations. As the donor cells of mitochondria, stem cells have biological advantages but research and evidence in this area are quite scarce. METHODS: To screen out suitable human autologous ooplasmic mitochondrial donor cells, we performed comprehensive assessment of mitochondrial physiology, function and metabolic capacity on a varity of autologous adipose, marrow, and urine-derived mesenchymal stromal cells (ADSC, BMSC and USC) and ovarian germline granulosa cells (GC). Further, to explore the biosafety, effect and mechanism of stem cell-derived mitochondria transfer on human early embryo development, randomized in-vitro basic studies were performed in both of the young and aged oocytes from infertile females. RESULTS: Compared with other types of mesenchymal stromal cells, USC demonstrated a non-fused spherical mitochondrial morphology and low oxidative stress status which resembled the oocyte stage. Moreover, USC mitochondrial content, activity and function were all higher than other cell types and less affected by age, and it also exhibited a biphasic metabolic pattern similar to the pre-implantation stage of embryonic development. After the biosafety identification of the USC mitochondrial genome, early embryos after USC mitochondrial transfer showed improvements in mitochondrial content, activity, and cytoplasmic Ca2+ levels. Further, aging embryos also showed improvements in embryonic morphological indicators, euploidy rates, and oxidative stress status. CONCLUSION: Autologous non-invasively derived USC mitochondria transfer may be an effective strategy to improve embryonic development and metabolism, especially in infertile females with advanced age or repeated pregnancy failure. It provides evidence and possibility for the autologous treatment of infertile females without invasive and ethical concerns.

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. METHODS: Mitochondria transplanted from different sources were initially tested in cultured hypertrophic cardiomyocytes. A right ventricular hypertrophy/right ventricular failure model created through banding of the pulmonary artery in immature piglets was used for treatment with autologous mitochondria (pulmonary artery banded mitochondria injected/treated n = 6) from calf muscle, versus vehicle (pulmonary artery banded vehicle injected/treated n = 6) injected into the right ventricular free-wall, and compared with sham-operated controls (sham, n = 6). Animals were followed for 8 weeks by echocardiography (free-wall thickness, contractility), and dp/dt max was measured concomitantly with cardiomyocyte hypertrophy, fibrosis, and apoptosis at study end point. RESULTS: Internalization of mitochondria and adenosine triphosphate levels did not depend on the source of mitochondria. At 4 weeks, banded animals showed right ventricular hypertrophy (sham: 0.28 ± 0.01 cm vs pulmonary artery banding: 0.4 ± 0.02 cm wall thickness; P = .001), which further increased in pulmonary artery banded mitochondria injected/treated but declined in pulmonary artery banded vehicle injected/treated (0.47 ± 0.02 cm vs 0.348 ± 0.03 cm; P = .01). Baseline contractility was not different but was significantly reduced in pulmonary artery banded vehicle injected/treated compared with pulmonary artery banded mitochondria injected/treated and so was dp/dtmax. There was a significant difference in apoptotic cardiomyocyte loss and fibrosis in sham versus hypertrophied hearts with most apoptosis in pulmonary artery banded vehicle injected/treated hearts (sham: 1 ± 0.4 vs calf muscle vs vehicle: 13 ± 1.7; P = .001 and vs pulmonary artery banded mitochondria injected/treated: 8 ± 1.9, P = .01; pulmonary artery banded vehicle injected/treated vs pulmonary artery banded mitochondria injected/treated, P = .05). CONCLUSIONS: Mitochondrial transplantation allows for prolonged physiologic adaptation of the pressure-loaded right ventricular and preservation of contractility by reducing apoptotic cardiomyocyte loss.

New Frontiers in IVF: mtDNA and autologous germline mitochondrial energy transfer.

Many infertility specialists support the existence of a relationship between the levels of mitochondrial DNA and the quality of the blastocysts. Despite the extensive use of pre-implantation genetic testing for aneuploidy, a significant percentage of euploid embryos do not implant even though the endometrium is normal. Mitochondrial DNA may be used as a new test in evaluating embryonic vitality.Ovarian aging leads to a decrease in the quantity and quality of oocytes and aged oocytes have a reduced number of mitochondria. Mitochondria are the energy factories of the cells and their lacked could leads to lower fertilization rates and poor embryonic development. Various strategies have been tested to increase the mitochondria quantity and thus improve the quality of oocytes used in in vitro fertilization. Results of ovarian rejuvenation techniques such as autologous mitochondrial transplantation have been controversial. In this review, we describe the state of the art concerning the use of mitochondrial DNA and autologous mitochondrial transplantation as new possibilities to increase success in vitro fertilization.

Mitochondria as a tool for oocyte rejuvenation.

Ovarian aging leads to a decrease in the quantity and quality of oocytes. Aged oocytes have significantly reduced amounts of mitochondria, the energy factories of cells, leading to lower fertilization rates and poor embryonic development. Various techniques have tried to use heterologous or autologous sources of mitochondria to reestablish oocyte health by providing more energy. However, heterologous sources are no longer used owing to the known risk of heteroplasmy. Although autologous methods have recently been tested in humans, they have not shown a clear improvement in embryo quality. In this review, we describe the techniques that have been tested in recent years to provide a state of the art on oocyte rejuvenation through extra injection of mitochondria.