A blended psychological intervention for postpartum depression: acceptability and preferences in women presenting depressive symptoms.

OBJECTIVES: To evaluate the acceptability of and preferences for a blended psychological intervention (combining face-to-face sessions and web-based interventions) for the treatment of postpartum depression among Portuguese women presenting depressive symptoms and to explore the factors associated with its acceptability. BACKGROUND: Despite its high prevalence and the existence of effective treatment, still few women seek professional help for postpartum depression, demanding for new treatment formats, such as blended interventions. METHODS: Women (n = 235) presenting postpartum depressive symptoms (EPDS>9) completed an internet survey assessing sociodemographic and clinical information, depressive symptoms, e-health literacy and the acceptability of and preferences for a blended intervention for postpartum depression. RESULTS: Most of the participants considered a blended intervention for postpartum depression to be useful and would be available to use it. Women reported significantly more advantages than disadvantages in regard to this treatment format. Married women, employed, with younger babies and with less severe depressive symptoms had a higher likelihood of finding a blended intervention useful. Higher educational levels increased the likelihood of being available to obtain a blended treatment. Most participants preferred an equal distribution of content across face-to-face and online sessions. Approximately one-third of the sample preferred a 75% face-to-face/ 25% online proportion. Most of the women preferred a duration of 45-60 minutes for face-to-face sessions and 30-45 minutes for online sessions. CONCLUSION: Our findings support and inform the development of blended psychological treatments for postpartum depression, according to women's preferences, and highlight the prioritisation of this format according to women's characteristics.

Central airway obstruction: is it time to move forward?

INTRODUCTION: Central airway obstruction (CAO) represents a pathological condition that can lead to airflow limitation of the trachea, main stem bronchi, bronchus intermedius or lobar bronchus. MAIN BODY: It is a common clinical situation consensually considered under-diagnosed. Management of patients with CAO can be difficult and deciding on the best treatment approach represents a medical challenge. This work intends to review CAO classifications, causes, treatments and its therapeutic limitations, approaching benign and malign presentations. Three illustrative cases are further presented, supporting the clinical problem under review. CONCLUSION: Management of CAO still remains a challenge. The available options are not always effective nor free from complications. A new generation of costume-tailored airway stents, associated with stem cell-based therapy, could be an option in specific clinical situations.

Gamma Irradiation Processing on 3D PCL Devices-A Preliminary Biocompatibility Assessment.

Additive manufacturing or 3D printing applying polycaprolactone (PCL)-based medical devices represents an important branch of tissue engineering, where the sterilization method is a key process for further safe application in vitro and in vivo. In this study, the authors intend to access the most suitable gamma radiation conditions to sterilize PCL-based scaffolds in a preliminary biocompatibility assessment, envisioning future studies for airway obstruction conditions. Three radiation levels were considered, 25 kGy, 35 kGy and 45 kGy, and evaluated as regards their cyto- and biocompatibility. All three groups presented biocompatible properties, indicating an adequate sterility condition. As for the cytocompatibility analysis, devices sterilized with 35 kGy and 45 kGy showed better results, with the 45 kGy showing overall improved outcomes. This study allowed the selection of the most suitable sterilization condition for PCL-based scaffolds, aiming at immediate future assays, by applying 3D-customized printing techniques to specific airway obstruction lesions of the trachea.

Peripheral Nerve Injury Treatments and Advances: One Health Perspective.

Peripheral nerve injuries (PNI) can have several etiologies, such as trauma and iatrogenic interventions, that can lead to the loss of structure and/or function impairment. These changes can cause partial or complete loss of motor and sensory functions, physical disability, and neuropathic pain, which in turn can affect the quality of life. This review aims to revisit the concepts associated with the PNI and the anatomy of the peripheral nerve is detailed to explain the different types of injury. Then, some of the available therapeutic strategies are explained, including surgical methods, pharmacological therapies, and the use of cell-based therapies alone or in combination with biomaterials in the form of tube guides. Nevertheless, even with the various available treatments, it is difficult to achieve a perfect outcome with complete functional recovery. This review aims to enhance the importance of new therapies, especially in severe lesions, to overcome limitations and achieve better outcomes. The urge for new approaches and the understanding of the different methods to evaluate nerve regeneration is fundamental from a One Health perspective. In vitro models followed by in vivo models are very important to be able to translate the achievements to human medicine.

3D Printed Poly(𝜀-caprolactone)/Hydroxyapatite Scaffolds for Bone Tissue Engineering: A Comparative Study on a Composite Preparation by Melt Blending or Solvent Casting Techniques and the Influence of Bioceramic Content on Scaffold Properties.

Bone tissue engineering has been developed in the past decades, with the engineering of bone substitutes on the vanguard of this regenerative approach. Polycaprolactone-based scaffolds are fairly applied for bone regeneration, and several composites have been incorporated so as to improve the scaffolds' mechanical properties and tissue in-growth. In this study, hydroxyapatite is incorporated on polycaprolactone-based scaffolds at two different proportions, 80:20 and 60:40. Scaffolds are produced with two different blending methods, solvent casting and melt blending. The prepared composites are 3D printed through an extrusion-based technique and further investigated with regard to their chemical, thermal, morphological, and mechanical characteristics. In vitro cytocompatibility and osteogenic differentiation was also assessed with human dental pulp stem/stromal cells. The results show the melt-blending-derived scaffolds to present more promising mechanical properties, along with the incorporation of hydroxyapatite. The latter is also related to an increase in osteogenic activity and promotion. Overall, this study suggests polycaprolactone/hydroxyapatite scaffolds to be promising candidates for bone tissue engineering, particularly when produced by the MB method.

Profiles of women with postpartum depressive symptoms: A latent profile analysis using the Edinburgh Postnatal Depression Scale factors.

OBJECTIVES: To examine the multidimensionality of symptoms assessed with the Edinburgh Postnatal Depression Scale (EPDS) and to identify and characterize the profiles of women with Postpartum Depression (PPD) symptoms. METHODS: A sample of 487 Portuguese postpartum women with clinically relevant depressive symptoms participated in this cross-sectional online study. Confirmatory factor analysis was conducted to analyze the factor structure of the EPDS. A latent profile analysis based on the EPDS factors was conducted. Differences in sociodemographic characteristics and risk factors between profiles were explored. RESULTS: Three EPDS factors were confirmed: depression, anxiety, and anhedonia. Based on these dimensions, three profiles with different symptom severities were found: mild anxious-depressive symptoms; severe PPD symptoms; and moderate anxious-depressive symptoms. CONCLUSION: Identifying profiles of women with PPD symptoms according to the EPDS factors allows to understand the distinct paths of development of PPD and can inform the development of tailored interventions.

Establishment of a Sheep Model for Hind Limb Peripheral Nerve Injury: Common Peroneal Nerve.

Thousands of people worldwide suffer from peripheral nerve injuries and must deal daily with the resulting physiological and functional deficits. Recent advances in this field are still insufficient to guarantee adequate outcomes, and the development of new and compelling therapeutic options require the use of valid preclinical models that effectively replicate the characteristics and challenges associated with these injuries in humans. In this study, we established a sheep model for common peroneal nerve injuries that can be applied in preclinical research with the advantages associated with the use of large animal models. The anatomy of the common peroneal nerve and topographically related nerves, the functional consequences of its injury and a neurological examination directed at this nerve have been described. Furthermore, the surgical protocol for accessing the common peroneal nerve, the induction of different types of nerve damage and the application of possible therapeutic options were described. Finally, a preliminary morphological and stereological study was carried out to establish control values for the healthy common peroneal nerves regarding this animal model and to identify preliminary differences between therapeutic methods. This study allowed to define the described lateral incision as the best to access the common peroneal nerve, besides establishing 12 and 24 weeks as the minimum periods to study lesions of axonotmesis and neurotmesis, respectively, in this specie. The post-mortem evaluation of the harvested nerves allowed to register stereological values for healthy common peroneal nerves to be used as controls in future studies, and to establish preliminary values associated with the therapeutic performance of the different applied options, although limited by a small sample size, thus requiring further validation studies. Finally, this study demonstrated that the sheep is a valid model of peripheral nerve injury to be used in pre-clinical and translational works and to evaluate the efficacy and safety of nerve injury therapeutic options before its clinical application in humans and veterinary patients.

In Vitro and In Vivo Characterization of PLLA-316L Stainless Steel Electromechanical Devices for Bone Tissue Engineering-A Preliminary Study.

Bone injuries represent a major social and financial impairment, commonly requiring surgical intervention due to a limited healing capacity of the tissue, particularly regarding critical-sized defects and non-union fractures. Regenerative medicine with the application of bone implants has been developing in the past decades towards the manufacturing of appropriate devices. This work intended to evaluate medical 316L stainless steel (SS)-based devices covered by a polymer poly (L-lactic acid) (PLLA) coating for bone lesion mechanical and functional support. SS316L devices were subjected to a previously described silanization process, following a three-layer PLLA film coating. Devices were further characterized and evaluated towards their cytocompatibility and osteogenic potential using human dental pulp stem cells, and biocompatibility via subcutaneous implantation in a rat animal model. Results demonstrated PLLA-SS316L devices to present superior in vitro and in vivo outcomes and suggested the PLLA coating to provide osteo-inductive properties to the device. Overall, this work represents a preliminary study on PLLA-SS316L devices' potential towards bone tissue regenerative techniques, showing promising outcomes for bone lesion support.

Postpartum Depression in the Portuguese Population: The Role of Knowledge, Attitudes and Help-Seeking Propensity in Intention to Recommend Professional Help-Seeking.

Professional help-seeking for postpartum depression is very uncommon, despite its adverse effects. However, women's support network can have an important role in the professional help-seeking behaviour. This study aimed to characterize the intentions to recommend professional help-seeking for postpartum depression in the Portuguese population, as well as to analyse its determinants. A cross-sectional internet survey including 621 people of general population was conducted. Participants reported a high intention to recommend professional help-seeking for postpartum depression. Greater knowledge about postpartum depression, lower stigma and high perceived utility of mental health help-seeking were associated with high intention to recommend professional help-seeking for PPD, both directly and indirectly, through less negative attitudes towards postpartum depression and higher help-seeking propensity. Education campaigns are needed to increase knowledge and to promote positive attitudes towards postpartum depression in the general population. Moreover, the results highlight the importance of implementing strategies aimed at reducing the stigma associated to help-seeking, of increasing the perception of utility of mental health services and of including the women's support network in perinatal care to facilitate their help-seeking process.

Self-criticism, negative automatic thoughts and postpartum depressive symptoms: the buffering effect of self-compassion.

Objective: This study aimed to explore the direct and indirect effects of self-criticism on postpartum depressive symptoms, through postpartum cognitions, and analyse the moderating role of self-compassion in this relationship. Background: Self-criticism and self-compassion are associated with postpartum depression. However, further research is needed to understand how these mechanisms operate in the development/maintenance of depressive symptoms. Methods: 686 women in the postpartum period (up to 12 months after birth) recruited in-person and online answered a cross-sectional survey. Results: The effect of self-criticism on postpartum depressive symptoms occurred sequentially, increasing the frequency of negative automatic thoughts and subsequently the metacognitive appraisal of these thoughts. Self-compassion had a moderating effect only on the relation between self-criticism and postpartum cognitions. The effect of self-criticism on postpartum cognitions decreased in the presence of higher self-compassion. Conclusion: This study emphasises the negative effect of a self-critical thinking style and of a negative appraisal of thought's content on depression symptoms. Moreover, this work underscores the buffering role of self-compassion in the relationship between self-criticism and postpartum cognitions. These results highlight the need to address the reduction of self-criticism and the promotion of self-compassion strategies to deal with postpartum cognitions, in order to prevent and treat postpartum depressive symptoms.

Psychometric properties of the Decisional Conflict Scale in a sample of perinatal women with depressive symptoms: A study in Portugal and Norway.

OBJECTIVE: To assess the psychometric properties, i.e., reliability and construct validity of the 16-item Decisional Conflict Scale (DCS) and sub-scales in women with perinatal depressive symptoms in Norway and Portugal. METHODS: We included 415 women in Portugal and 163 in Norway (≥18 years) who were pregnant or had given birth in the last 12 months and presenting with active depressive symptoms. Women replied to the original DCS items. We conducted confirmatory factor analysis, estimated internal consistency reliability, and examined factorial invariance across country, perinatal status, and treatment uptake. RESULTS: The DCS factor model had good fit to the data, with all items loading significantly on their respective factor (.585 to .958). There was configural invariance of the DCS across countries, treatment, and perinatal status. The internal consistency of the total DCS (Cronbach's alpha) was .958, and for the subscales it ranged from .798 to .947. CONCLUSIONS: The DCS is a valid and reliable measure of the decisional conflict in women with perinatal depressive symptoms in Portugal and Norway. PRACTICE IMPLICATIONS: Measuring the extent of decisional conflict regarding treatment and the effect of multiple interventions towards its reduction, is critical to facilitate the decision-making process of women with perinatal mental illness.

Treatment of Equine Tarsus Long Medial Collateral Ligament Desmitis with Allogenic Synovial Membrane Mesenchymal Stem/Stromal Cells Enhanced by Umbilical Cord Mesenchymal Stem/Stromal Cell-Derived Conditioned Medium: Proof of Concept.

Horses are high-performance athletes prone to sportive injuries such as tendonitis and desmitis. The formation of fibrous tissue in tendon repair remains a challenge to overcome. This impels regenerative medicine to develop innovative therapies that enhance regeneration, retrieving original tissue properties. Multipotent Mesenchymal Stem/Stromal Cells (MSCs) have been successfully used to develop therapeutic products, as they secrete a variety of bioactive molecules that play a pivotal role in tissue regeneration. These factors are released in culture media for producing a conditioned medium (CM). The aforementioned assumptions led to the formulation of equine synovial membrane MSCs (eSM-MSCs)-the cellular pool that naturally regenerates joint tissue-combined with a medium enriched in immunomodulatory factors (among other bioactive factors) produced by umbilical cord stroma-derived MSCs (eUC-MSCs) that naturally contribute to suppressing the immune rejection in the maternal-fetal barrier. A description of an equine sport horse diagnosed with acute tarsocrural desmitis and treated with this formulation is presented. Ultrasonographic ligament recovery occurred in a reduced time frame, reducing stoppage time and allowing for the horse's return to unrestricted competition after the completion of a physical rehabilitation program. This study focused on the description of the therapeutic formulation and potential in an equine desmitis treatment using the cells themselves and their secretomes.

Generation and characterization of cortical organoids from iPSC-derived dental pulp stem cells using traditional and innovative approaches.

Cortical organoids derived from human induced pluripotent stem cells (hiPSCs) represent a powerful in vitro experimental system to investigate human brain development and disease, often inaccessible to direct experimentation. However, despite steady progress in organoid technology, several limitations remain, including high cost and variability, use of hiPSCs derived from tissues harvested invasively, unexplored three-dimensional (3D) structural features and neuronal connectivity. Here, using a cost-effective and reproducible protocol as well as conventional two-dimensional (2D) immunostaining, we show that cortical organoids generated from hiPSCs obtained by reprogramming stem cells from human exfoliated deciduous teeth (SHED) recapitulate key aspects of human corticogenesis, such as polarized organization of neural progenitor zones with the presence of outer radial glial stem cells, and differentiation of superficial- and deep-layer cortical neurons and glial cells. We also show that 3D bioprinting and magnetic resonance imaging of intact cortical organoids are alternative and complementary approaches to unravel critical features of the 3D architecture of organoids. Finally, extracellular electrical recordings in whole organoids showed functional neuronal networks. Together, our findings suggest that SHED-derived cortical organoids constitute an attractive model of human neurodevelopment, and support the notion that a combination of 2D and 3D techniques to analyze organoid structure and function may help improve this promising technology.

Treatment options and their uptake among women with symptoms of perinatal depression: exploratory study in Norway and Portugal.

BACKGROUND: Perinatal depression is the most undertreated clinical condition during the perinatal period. Knowledge about women's decision-making in seeking and receiving treatment is scarce. AIMS: To investigate and compare treatment option uptake in perinatal women with depressive symptoms in Portugal and Norway, and to identify sociodemographic and health-related factors associated with treatment uptake. METHOD: Participants were women resident in Portugal or Norway (≥18 years) who were pregnant or had given birth in the past 12 months, who presented with active depressive symptoms (Edinburgh Postnatal Depression Scale score ≥10). In an electronic questionnaire, women reported treatment received and sociodemographic and health-related factors. RESULTS: The sample included 416 women from Portugal and 169 from Norway, of which 79.8% and 53.9%, respectively, were not receiving any treatment. Most Portuguese women were receiving psychological treatment, either alone (45.2%) or combined with pharmacological treatment (21.4%). Most Norwegian participants were receiving only pharmacological (36.5%) or combined treatment (35.4%). Compared with the Portuguese sample, a higher proportion of Norwegian women started treatment before pregnancy (P < 0.001). In Portugal, lower depressive symptoms and self-reported psychopathology were significantly associated with higher likelihood of receiving treatment. CONCLUSIONS: We found that, in both Norway and Portugal, a substantial number of perinatal women with depressive symptoms do not receive any treatment. Differences exist regarding the chosen treatment option and timing of treatment initiation in the two countries. Only mental health-related factors were associated with treatment uptake for perinatal depression in Portugal. Our results highlight the importance of implementing strategies aimed to improve help-seeking behaviours.

Dysfunctional Attitudes Toward Motherhood and Depressive Symptoms in Portuguese Pregnant Women During COVID-19 Pandemic: the Mediating Roles of Self-Compassion and Mindful Self-Care.

Objectives: There is evidence that the coronavirus disease 2019 (COVID-19) pandemic had a negative impact on the mental health of pregnant women, such as an increase in the prevalence of depression. Given the negative consequences that depressive symptoms can pose for pregnant women, it is crucial to understand how cognitive processes influence women's depressive symptoms during the COVID-19 pandemic among this specific vulnerable population. The present study aimed to examine the relationship between pregnant women's dysfunctional attitudes toward motherhood and their depressive symptoms, considering the mediating roles of self-compassion and mindful self-care. Method: A cross-sectional online survey was conducted in Portugal between October 2020 and April 2021. A sample of 244 pregnant women answered a set of questionnaires to assess dysfunctional attitudes toward motherhood, depressive symptoms, self-compassion, and mindful self-care. Results: More dysfunctional attitudes toward motherhood were associated with higher levels of depressive symptoms, and this relation was mediated through self-compassion and mindful self-care. Conclusions: These results highlight that self-compassion and mindful self-care are important psychological mechanisms and the importance of considering them in psychological interventions to prevent and/or treat depressive symptoms in pregnant women with dysfunctional attitudes toward motherhood during stressful events such as a pandemic.

Allogenic Synovia-Derived Mesenchymal Stem Cells for Treatment of Equine Tendinopathies and Desmopathies-Proof of Concept.

Tendon and ligament injuries are frequent in sport horses and humans, and such injuries represent a significant therapeutic challenge. Tissue regeneration and function recovery are the paramount goals of tendon and ligament lesion management. Nowadays, several regenerative treatments are being developed, based on the use of stem cell and stem cell-based therapies. In the present study, the preparation of equine synovial membrane mesenchymal stem cells (eSM-MSCs) is described for clinical use, collection, transport, isolation, differentiation, characterization, and application. These cells are fibroblast-like and grow in clusters. They retain osteogenic, chondrogenic, and adipogenic differentiation potential. We present 16 clinical cases of tendonitis and desmitis, treated with allogenic eSM-MSCs and autologous serum, and we also include their evaluation, treatment, and follow-up. The concerns associated with the use of autologous serum as a vehicle are related to a reduced immunogenic response after the administration of this therapeutic combination, as well as the pro-regenerative effects from the growth factors and immunoglobulins that are part of its constitution. Most of the cases (14/16) healed in 30 days and presented good outcomes. Treatment of tendon and ligament lesions with a mixture of eSM-MSCs and autologous serum appears to be a promising clinical option for this category of lesions in equine patients.

Intensive neurorehabilitation and allogeneic stem cells transplantation in canine degenerative myelopathy.

Introduction: Degenerative myelopathy (DM) is a neurodegenerative spinal cord disease with upper motor neurons, with progressive and chronic clinical signs, similar to amyotrophic lateral sclerosis (ALS). DM has a complex etiology mainly associated with SOD1 gene mutation and its toxic role, with no specific treatment. Daily intensive rehabilitation showed survival time near 8 months but most animals are euthanized 6-12 months after clinical signs onset. Methods: This prospective controlled blinded cohort clinical study aims to evaluate the neural regeneration response ability of DM dogs subjected to an intensive neurorehabilitation protocol with mesenchymal stem cells (MSCs) transplantation. In total, 13 non-ambulatory (OFS 6 or 8) dogs with homozygous genotype DM/DM and diagnosed by exclusion were included. All were allocated to the intensive neurorehabilitation with MSCs protocol (INSCP) group (n = 8) or to the ambulatory rehabilitation protocol (ARP) group (n = 5), which differ in regard to training intensity, modalities frequency, and MSCs transplantation. The INSCP group was hospitalized for 1 month (T0 to T1), followed by MSCs transplantation (T1) and a second month (T2), whereas the ARP group was under ambulatory treatment for the same 2 months. Results: Survival mean time of total population was 375 days, with 438 days for the INSCP group and 274 for the ARP group, with a marked difference on the Kaplan-Meier survival analysis. When comparing the literature's results, there was also a clear difference in the one-sample t-test (p = 0.013) with an increase in time of approximately 70%. OFS classifications between groups at each time point were significantly different (p = 0.008) by the one-way ANOVA and the independent sample t-test. Discussion: This INSCP showed to be safe, feasible, and a possibility for a long progression of DM dogs with quality of life and functional improvement. This study should be continued.

Frontline health professionals' perinatal depression literacy: A systematic review.

BACKGROUND: Perinatal depression is a highly prevalent mental health problem with severe consequences, which is still underdiagnosed and undertreated. Frontline health professionals directly assisting and providing regular care to women in pregnancy and postpartum period play a critical role in early detection and management of perinatal depression. Therefore, it is important to assess their knowledge and beliefs towards perinatal depression, in order to improve its recognition and management. OBJECTIVE: To synthesize the current literature about the levels of perinatal depression literacy (defined in terms of recognition and knowledge of symptoms, causes, risk factors and treatment options, beliefs, and attitudes) among frontline health professionals working with perinatal women. DESIGN: A systematic review of the literature was conducted in line with PRISMA guidelines and registered in PROSPERO (CRD42020172018). Six electronic databases were searched for eligible studies. Quantitative and qualitative studies published in English reporting findings on perinatal depression literacy among health professionals working with perinatal population were included. Pharmacists, medical or nursing students, volunteer workers, religious leaders, community leader and birth attendants were excluded from the target population. Included studies were assessed for risk of bias. FINDINGS: From the 3172 papers screened, a total of 43 were included. All studies were classified with strong or moderate quality. Frontline health professionals presented average levels of perinatal depression literacy. However, a lack of knowledge about the definition, prevalence, symptoms, risk factors, screening tools and treatments for perinatal depression was found in several studies, which could act as barriers to providing proper care to perinatal women. Health professionals' knowledge and attitudes seemed to differ across countries. IMPLICATIONS FOR PRACTICE: The findings of this systematic review highlight the need to provide health professionals with training to increase their levels of knowledge about perinatal depression and to promote more positive attitudes towards it, which can potentially increase their confidence and skills in its management and treatment.

Mattering and Depressive Symptoms in Portuguese Postpartum Women: The Indirect Effect of Loneliness.

BACKGROUND: Postpartum depression is described as the most prevalent clinical condition in the postpartum period, with several negative consequences. The current study aimed to understand the relationship between mattering, loneliness and depressive symptoms in Portuguese postpartum women and to examine the potential mediating role of loneliness in the relationship between mattering and depressive symptomatology among postpartum women. METHODS: This cross-sectional study included a sample collected online composed of 530 Portuguese women in the postpartum period, who answered self-report questionnaires to assess depressive symptoms, mattering, and loneliness. RESULTS: It was found that the relationships between mattering, loneliness, and depressive symptoms were significant, p < 0.001: (a) higher levels of mattering were associated with lower levels of loneliness and depressive symptomatology and (b) higher levels of loneliness were associated with higher levels of depressive symptomatology. The relationship between mattering and postpartum depressive symptoms occurred directly and indirectly through loneliness, 95% CI = [-0.75, -0.46]. CONCLUSIONS: These results highlight the importance of studying loneliness as a possible risk factor for postpartum depression and alert to the pertinence of considering mattering and loneliness in the assessment and intervention with women in the perinatal period.

Mesenchymal Stem/Stromal Cells and Their Paracrine Activity-Immunomodulation Mechanisms and How to Influence the Therapeutic Potential.

With high clinical interest to be applied in regenerative medicine, Mesenchymal Stem/Stromal Cells have been widely studied due to their multipotency, wide distribution, and relative ease of isolation and expansion in vitro. Their remarkable biological characteristics and high immunomodulatory influence have opened doors to the application of MSCs in many clinical settings. The therapeutic influence of these cells and the interaction with the immune system seems to occur both directly and through a paracrine route, with the production and secretion of soluble factors and extracellular vesicles. The complex mechanisms through which this influence takes place is not fully understood, but several functional manipulation techniques, such as cell engineering, priming, and preconditioning, have been developed. In this review, the knowledge about the immunoregulatory and immunomodulatory capacity of MSCs and their secretion products is revisited, with a special focus on the phenomena of migration and homing, direct cell action and paracrine activity. The techniques for homing improvement, cell modulation and conditioning prior to the application of paracrine factors were also explored. Finally, multiple assays where different approaches were applied with varying success were used as examples to justify their exploration.