Mesenchymal stem cell-mediated transfer of mitochondria: mechanisms and functional impact.

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.

Is bariatric surgery improving mitochondrial function in the renal cells of patients with obesity-induced kidney disease?

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.

Primary allogeneic mitochondrial mix (PAMM) transfer/transplant by MitoCeption to address damage in PBMCs caused by ultraviolet radiation.

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.

Early evidence of the artificial transfer/transplant of mitochondria to oocytes and zygotes by MitoCeption.

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.

Use of Human Umbilical Cord and Its Byproducts in Tissue Regeneration.

The fresh or cryopreserved human umbilical cord (HUC) and its byproducts, such as cells and extracts, have different uses in tissue regeneration. Defining what HUC byproduct is more effective in a particular application is a challenge. Furthermore, the methods of isolation, culture and preservation, may affect cell viability and regenerative properties. In this article, we review the HUC and its byproducts' applications in research and clinical practice. We present our results of successful use of HUC as a patch to treat gastroschisis and its potential to be applied in other conditions. Our in vitro results show an increase in proliferation and migration of human fibroblasts by using an acellular HUC extract. Our goal is to promote standardization of procedures and point out that applications of HUC and its byproducts, as well as the resulting advances in regenerative medicine, will depend on rigorous quality control and on more research in this area.

Ring chromosome 15 - cytogenetics and mapping arrays: a case report and review of the literature.

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.