Search

Oocytes may carry mutations in their mitochondrial DNA (mtDNA) which affect fertility and embryo development leading to hereditary diseases or rejection. Mitochondrial replacement therapies (MRTs) such as polar body transfer, spindle transfer and pronuclear transfer, aim to change dysfunctional to normal mitochondria inside oocytes and zygotes resulting in healthier offspring. Even with promising results, MRTs techniques are invasive to oocytes and may negatively affect their viability and the success of the procedure. This article shows early evidence of the use of MitoCeption, a mitochondria transfer/transplant (AMT/T) technique to possibly induce the internalization of exogenous mitochondria in a dose-dependent manner to recipient oocytes in comparison to coincubation. By using human isolated mitochondria in a mix obtained from different donors we were able to identify their mtDNA in murine oocytes by qPCR. Fluorescence microscopy showed that exogenous and transferred mitochondria (MitoTracker ® Red) by MitoCeption were internalized in oocytes and zygotes (CellTracker® Green). After maintaining mitocepted zygotes to two-cell embryos, we transferred them to subrogate female mice and obtained healthy mice pups; however, without clear evidence of the maintenance of human mtDNA in the tissues of mice pups. These early results are puzzling, and they open the path to generate more research regarding the use of MitoCeption in comparison to coincubation in order to transfer mitochondria to oocytes using less invasive procedures.

There is a steadily growing interest in the use of mitochondria as therapeutic agents. The use of mitochondria derived from mesenchymal stem/stromal cells (MSCs) for therapeutic purposes represents an innovative approach to treat many diseases (immune deregulation, inflammation-related disorders, wound healing, ischemic events, and aging) with an increasing amount of promising evidence, ranging from preclinical to clinical research. Furthermore, the eventual reversal, induced by the intercellular mitochondrial transfer, of the metabolic and pro-inflammatory profile, opens new avenues to the understanding of diseases' etiology, their relation to both systemic and local risk factors, and also leads to new therapeutic tools for the control of inflammatory and degenerative diseases. To this end, we illustrate in this review, the triggers and mechanisms behind the transfer of mitochondria employed by MSCs and the underlying benefits as well as the possible adverse effects of MSCs mitochondrial exchange. We relay the rationale and opportunities for the use of these organelles in the clinic as cell-based product.

The role of mitochondria in health and disease has dramatically changed in the last decade. Its complex integration into cell physiology is comprised of key metabolic functions of great importance in health maintenance. Treating obesity seems to improve overall mitochondria tissue malfunction; however, the extent of their impact on patients remains elusive due to the lack of follow-up studies. It has been observed that procedures such as bariatric surgery (BS) can modify how our body absorbs nutrients, influencing metabolic processes and mitochondrial function in several cells and tissues. In fact, tissue analysis performed in vivo and in patients support that BS mitigates mitochondrial dysfunction in obese subjects. BS has been observed to reduce the presence of comorbidities such as type 2 diabetes (T2D) and hypertension (HTN) in patients. It is still unclear how BS specifically affects mitochondrial dynamics in obesity-induced comorbidities such as kidney disease. This article provides insightful information regarding the amelioration of mitochondrial dynamics in renal cells and systems after BS. Understanding the multiple pathways that lead to mitochondrial dysregulation in obesity-related kidney disease and relating them to the positive molecular changes after BS may lead to the development of adjuvant therapies to control this and other conditions with similar pathophysiological backgrounds.

Background Artificial Mitochondrial Transfer or Transplant (AMT/T) can be used to reduce the stress and loss of viability of damaged cells. In MitoCeption, a type of AMT/T, the isolated mitochondria and recipient cells are centrifuged together at 4 °C and then co-incubated at 37 °C in normal culture conditions, inducing the transfer. Ultraviolet radiation (UVR) can affect mitochondria and other cell structures, resulting in tissue stress, aging, and immunosuppression. AMT/T could be used to repair UVR cellular and mitochondrial damage. We studied if a mitochondrial mix from different donors (Primary Allogeneic Mitochondrial Mix, PAMM) can repair UVR damage and promote cell survival. Results Using a simplified adaption of the MitoCeption protocol, we used peripheral blood mononuclear cells (PBMCs) as the recipient cell model of the PAMM in order to determine if this protocol could repair UVR damage. Our results showed that when PBMCs are exposed to UVR, there is a decrease in metabolic activity, mitochondrial mass, and mtDNA sequence stability as well as an increase in p53 expression and the percentage of dead cells. When PAMM MitoCeption was used on UVR-damaged cells, it successfully transferred mitochondria from different donors to distinct PBMCs populations and repaired the observed UVR damage. Conclusion Our results represent an advancement in the applications of MitoCeption and other AMT/T. We showed that PBMCs could be used as a PAMM source of mitochondria. We also showed that these mitochondria can be transferred in a mix from different donors (PAMM) to UVR-damaged, non-adherent primary cells. Additionally, we decreased the duration of the MitoCeption protocol. Electronic supplementary material The online version of this article (10.1186/s12896-019-0534-6) contains supplementary material, which is available to authorized users.

© The Author(s)., [Background]: Ring chromosome 15 has been associated in previous studies with different clinical characteristic such as cardiac problems, digit and musculoskeletal abnormalities, and mental and motor problems among others. Only 97 clinical cases of ring chromosome 15 syndrome have been reported since 1966 and a common phenotype for these patients has not been established., [Case presentation]: The present case report describes a 15-month-old girl from the Amazon region of Ecuador, of Mestizo ancestry, who after cytogenetic tests showed a 46,XX,r(15) karyotype in more than 70% of metaphases observed. Her parents were healthy and non-related. The pregnancy was complicated and was positive for intrauterine growth retardation. Her birth weight was 1950 g, her length was 43.5 cm, and she had a head circumference of 29.3. In addition to postnatal growth delay, she had scant frontal hair, small eyes, hypertelorism, low-set of ears, flattened nasal bridge, anteverted nostrils, down-turned mouth, three café au lait spots, and delayed dentition., [Conclusions]: Despite the frequency of some phenotypes expressed in the different clinical cases reviewed and the present case, a common phenotype for patients with ring 15 could not be determined and it is restricted to the region of the chromosome lost during the ring formation., Funding for this research was completely managed by the institutions affiliated. Centro de Investigación Genética y Genómica, Facultad de Ciencias de la Salud Eugenio Espejo, Universidad UTE, Quito, Ecuador. Facultad de Ciencias de la Salud, Universidad San Francisco de Quito, Quito, Ecuador. Unidad de Investigación en Biomedicina, Zurita & Zurita Laboratorios, Quito, Ecuador. Servicio de Hematología, Hospital Universitario de Salamanca, Universidad de Salamanca, Salamanca, Spain. Molecular Medicine Unit, Department of Medicine, Biomedical Research Institute of Salamanca (IBSAL), Salamanca, Spain. Institute of Molecular and Cellular Biology of Cancer (IBMCC), University of Salamanca-SACYL-CSIC, Salamanca, Spain.