In this study, we developed a methodology to improve the survival, vascular differentiation and regenerative potential of umbilical cord blood (UCB)-derived hematopoietic stem cells (CD34+ cells), by co-culturing the stem cells in a 3D fibrin gel with CD34+-derived endothelial cells (ECs). ECs differentiated from CD34+ cells appear to have superior angiogenic properties to fully differentiated ECs, such as human umbilical vein endothelial cells (HUVECs). Our results indicate that the pro-survival effect of CD34+-derived ECs on CD34+ cells is mediated, at least in part, by bioactive factors released from ECs. This effect likely involves the secretion of novel cytokines, including interleukin-17 (IL-17) and interleukin-10 (IL-10), and the activation of the ERK 1/2 pathway in CD34+ cells. We also show that the endothelial differentiation of CD34+ cells in co-culture with CD34+-derived ECs is mediated by a combination of soluble and insoluble factors. The regenerative potential of this co-culture system was demonstrated in a chronic wound diabetic animal model. The co-transplantation of CD34+ cells with CD34+-derived ECs improved the wound healing relatively to controls, by decreasing the inflammatory reaction and increasing the neovascularization of the wound.

Betacoronavirus (β-CoV) are positive single-stranded RNA viruses known to infect mammals. In 2019, a novel zoonotic β-CoV emerged, the severe acute respiratory syndrome (SARS)-CoV-2. Although the most frequent SARS-CoV-2 transmission route is within humans, spillover from humans to domestic and wild animals has been reported, including cats (Felis catus), dogs (Canis lupus familiaris), and minks (Neovision vision). In order to understand the potential role of domestic animals in SARS-CoV-2 global transmission, as well their susceptibility to infection, a seroepidemiologic survey of cats and dogs in Portugal was conducted. Antibodies against SARS-CoV-2 were detected in 15/69 (21.74%) cats and 7/148 (4.73%) dogs. Of the SARS-CoV-2 seropositive animals, 11/22 (50.00%) were possibly infected by human-to-animal transmission, and 5/15 (33.33%) cats were probably infected by cat-to-cat transmission. Moreover, one dog tested positive for SARS-CoV-2 RNA. Data suggest that cats and dogs are susceptible to SARS-CoV-2 infection in natural conditions. Hence, a one-health approach is crucial in the SARS-CoV-2 pandemic to understand the risk factors beyond infection in a human–animal environment interface.

Several clinical trials are exploring therapeutic effect of human CD34+ cells in ischemic diseases, including myocardial infarction. Unfortunately, most of the cells die few days after delivery. Herein we show that lysophosphatidic acid (LPA)-treated human umbilical cord blood-derived CD34+ cells cultured under hypoxic and serum-deprived conditions present 2.2-fold and 1.3-fold higher survival relatively to non-treated cells and prostaglandin E2-treated cells, respectively. The pro-survival effect of LPA is concentration- and time-dependent and it is mediated by the activation of peroxisome proliferator-activator receptor γ (PPARγ) and downstream, by the activation of pro-survival ERK and Akt signaling pathways and the inhibition of mitochondrial apoptotic pathway. In hypoxia and serum-deprived culture conditions, LPA induces CD34+ cell proliferation without maintaining the their undifferentiating state, and enhances IL-8, IL-6 and G-CSF secretion during the first 12 h compared to non-treated cells. LPA-treated CD34+ cells delivered in fibrin gels have enhanced survival and improved cardiac fractional shortening at 2 weeks on rat infarcted hearts as compared to hearts treated with placebo. We have developed a new platform to enhance the survival of CD34+ cells using a natural and cost-effective ligand and demonstrated its utility in the preservation of the functionality of the heart after infarction.

EIAV is a monocyte/macrophage tropic virus. To date, even though EIAV has been under investigation for numerous years, very few details have been elucidated about EIAV/macrophage interactions. This is largely due to the absence of an equine macrophage cell line that would support viral replication. Herein we describe the spontaneous immortalization and generation of a clonal equine macrophage-like (EML) cell line with the functional and immunophenotype characteristics of differentiated equine monocyte derived macrophage(s) (eMDM(s)). These cells possess strong non-specific esterase (NSE) activity, are able to phagocytose fluorescent bioparticles, and produce nitrites in response to LPS. The EML-3C cell line expresses the EIAV receptor for cellular entry (ELR1) and supports replication of the virulent EIAV PV biological clone. Thus, EML-3C cells provide a useful cell line possessing equine macrophage related properties for the growth and study of EIAV infection as well as of other equine macrophage tropic viruses.

Recent pre-clinical and clinical studies indicate that certain exogenous stem cells and biomaterials can preserve cardiac tissue after myocardial infarction. Regarding stem cells, a growing body of data suggests that the short-term positive outcomes are mainly attributed to paracrine signaling mechanisms. The release of such factors is due to the cell’s ability to sense cardiac environmentally derived cues, though the exact feedback loops are still poorly understood. However, given the limited engraftment and survival of transplanted cells in the ischemic environment, the long-term clinical benefits of these therapies have not yet been realized. To overcome this, the long-term controlled delivery of bioactive factors using biomaterials is a promising approach. A major challenge has been the ability to develop timely and spatially controlled gradients of different cues, pivotal for the development and regeneration of tissues. In addition, given the complexity of the remodeling process after myocardial infarction, multiple factors may be required at distinct disease stages to maximize therapeutic outcomes. Therefore, novel smart materials that can sense the surrounding environment and generate cues through on demand mechanisms will be of major importance in the translation of these promising advanced therapies. This article reviews how the cardiac environment can mediate the release profiles of bioactive cues from cells and biomaterials and how the controlled delivery impacts heart regeneration.