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Primo Vascular System in Human Umbilical Cord and Placenta

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The primo vascular system (PVS) has been observed in various animals like mice, rats, rabbits, dogs, swine, and cow, but not in human subjects. In this work, we report the observation of a human PVS that was present on the epithelial fascia of, and inside the blood vessels of, an umbilical cord. The main morphological characteristics of the primo vessels (PVs) and primo nodes (PNs) from the human umbilical cord were in agreement with those of the PVS in various animal organs: The thicknesses and the transparency of the PVs, the sizes of the PNs, the broken-line arrangement of the rod-shaped nuclei, and the sparse distribution of nuclei and the presence of hollow lumens in the central inner parts of the PNs were consistent with those of animal PVSs. It was rather surprising that the human PV was not thicker than the PVs from small animals. The difference of the PVSs from either blood or lymph vessels was confirmed by using immunofluorescence staining of vWF, CD31, LYVE-1, and D2-40. The positive expression to the cell proliferation marker PCNA was consistent with the recent finding of very small embryonic-like stem cells in the PVS of mice.
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... Since 2010, the novel anatomical structure is termed "primo vascular system" (PVS) comprising "primo vessels" (PVs) and "primo nodes" (PNs), distributed throughout the entire body [1]. The PVS has been detected in several different types of animals as well as in different tissues and systems, e.g. at the surface of organs [2] [3] [4] [5] [6] [7] [8], the inner abdominal wall [9] [8] [10], inside and along blood vessels [11] [12] [13], inside lymphatic vessels [14] [15] [16] [13] [17] [18] [19] [20], in the endocardia of atrium and ventricles of the heart [11] [21], in adipose tissue [22], along the central canal [23] and around the perineurium of the spinal cord [24], in the cerebrospinal fluid of the brain ventricles [23], in the arachnoid mater of the brain [24], along the sciatic nerve [25], in the fascia along skin skeletal muscles in the hypodermal layer [26], as well as at the surface of the umbilical cord [27] and placenta [27] [28]. These reports found that the thickness of the PVs is about 20-150 µm with a length of up to several centimeters. ...
... Since 2010, the novel anatomical structure is termed "primo vascular system" (PVS) comprising "primo vessels" (PVs) and "primo nodes" (PNs), distributed throughout the entire body [1]. The PVS has been detected in several different types of animals as well as in different tissues and systems, e.g. at the surface of organs [2] [3] [4] [5] [6] [7] [8], the inner abdominal wall [9] [8] [10], inside and along blood vessels [11] [12] [13], inside lymphatic vessels [14] [15] [16] [13] [17] [18] [19] [20], in the endocardia of atrium and ventricles of the heart [11] [21], in adipose tissue [22], along the central canal [23] and around the perineurium of the spinal cord [24], in the cerebrospinal fluid of the brain ventricles [23], in the arachnoid mater of the brain [24], along the sciatic nerve [25], in the fascia along skin skeletal muscles in the hypodermal layer [26], as well as at the surface of the umbilical cord [27] and placenta [27] [28]. These reports found that the thickness of the PVs is about 20-150 µm with a length of up to several centimeters. ...
... Despite the many investigations of the PVS published by different research groups in animals (e.g. rats, rabbits, cows, mice, dogs, pigs) and even samples of human tissue (umbilical cord and placenta [27]) with modern histological, immunochemistry and diverse microscopic techniques, the PVS is not well known by Western scientists, or if known, is generally viewed with skepticism. The lack of publications about the PVS in high-impact scientific journals as yet, the publication of the research results often in alternative medicine journals, as well the current lack of research on the PVS by Western scientists, seem to be the main reasons for it. ...
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For many years, reports have been published describing the discovery and investigation of an additional vascular system in mammals. This primo vascular system (PVS) is distinct from the blood and lymph vascular system and consists of primo nodes (PNs) and primo vessels (PVs) as its main constituents. We investigated samples of the PVS from the intestine surface of rats and observed several instances of a red thread-like structure (RTLS) and a red oval or round structure (RORS) in PVs and PNs, respectively. We conclude that the RTLS and RORS are most likely due to erythrocytes, indicating the occurrence of extramedullary hematopoiesis inside the PVS of the intestine surface. To the best of our knowledge, this is the first report showing detailed microscopic images of an RTLS traversing four PNs and a single PV. Our report is intended to document our findings and also to motivate others to repeat and extend our study in order to investigate in detail the possible extramedullary hematopoiesis occurring inside the PVS.
... The reason that human placenta tissue was used in this study was that the staining methods to identify the new structure were previously performed in different in vivo animal studies and it was argued that these staining techniques would not be successful in postmortem tissues. (Lee et al., 2014). As such, it remains unknown whether the Bonghan system/primo vascular system is indeed present inside the human lymphatic system, but future research efforts, might shed some light on this topic. ...
... Another interesting thought when using micro CT imaging, would be to focus on the primo vascular structures that are supposedly present within lymphatic vessels and a contrasting technique in combination with micro CT imaging could possibly succeed in a post-mortem setting. Instead of using the staining and imaging approaches that are only expected to work during in vivo animal experiments (Lee et al., 2014), filling the lymphatic vessel with barium sulphate for micro CT imaging could in fact show a structure with a mean diameter of 129 µm and diameters of up to 500 µm in rabbits (Lee et al., 2005), simply because it will not take up the barium sulphate. If the primo vascular system is indeed not able to incorporate the barium sulphate, it is expected to show a dark shadow on the micro CT images, surrounded by the bright white contrast of the barium sulphate surrounding it. ...
... Endothelial cells line the sinuses of the primo vessels. Specifically, each sinus (small ductile) is lined with a single, non-fenestrated endothelial cell [6,11]. The nuclei of these endothelial cells are rod-shaped and arranged in parallel, broken-line fashion along the primo vessel (Fig. 1A, 2) [12][13][14]. ...
... Also, negative expression was observed in the primo vessels for the lymph vessel, endothelial cell marker, LYVE-1. This indicates that the primo vessel endothelium differs from those of the blood vessels and lymph vessels [11]. ...
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The primo vascular system (PVS) is of great interest to scientists in the last few years. The PVS plays a role in stem cell migration, immune function, erythropoiesis, tissue regeneration, and cancer metastasis. Discovered by Bong Han Kim in 1960, the PVS was described as a new, independent system that is distributed in the body of different animals. Since then, several cells have been discovered as important constituents of the PVS. Endothelial cells are hallmarks for the identification of the PVS, as they line the sinuses of the primo vessels and are characterized by their arrangement of rod-shaped nuclei in a parallel, broken-line fashion along the primo vessels. Immune cells as mast cells, eosinophils, neutrophils, and lymphocytes are also hallmarks for the identification of the PVS. One of the most interesting cells in the PVS are p-microcells. Primo nodes are a stem cell niche due to their p-microcells content, which express stem cell biomarkers CD133 and Oct 4. Mature erythrocytes and hematopoietic stem cells have also been observed in the PVS. Hematopoietic stem cells were observed in the PVS. Hematopoietic Stem Cells are the source of the cellular component of blood. Additionally, adrenaline and noradrenaline-producing cells, mesothelial cells, and smooth-muscle-like cells have also been described in the PVS.
... Studies confirm the presence of the PVS in the heart, liver, small intestine, stomach and gall bladder, as well as in blood and lymph vessels, skin and adipose tissue, and the central and peripheral nervous systems (Cai et al. 2013;Soh et al. 2013). Confirmation of its presence in human fascia and blood vessels has been demonstrated by Lee et al. (2014). ...
... The PVS is described as a complicated network of nodes and vessels, and is identifiable by endothelial cells which have rod-shaped nuclei aligned in broken lines (Soh 2009;Lee et al. 2014). These cells line up parallel to the primo vessel walls, and are difficult to identify in cross-sectional images (Chickly et al. 2016). ...
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Over the last 20 years there have been advances in understanding the biochemical reactions involved in acupuncture, and attempts made to link traditional Chinese medical theories to scientific findings. The meridians have been linked to tissues in the body including perfora-tor blood vessels, the primo vascular system, the interstitial space and fascia. These tissues have, in the main, been linked to meridian theory independently, with discussion of overlapping areas in a few articles. This article attempts to describe these structures and tissue systems and analyze the similarities between them, linking them to Chinese concepts around acupuncture such as the meridians. This paper theorizes that the substrate of the meridians and flow of Blood and Qi is due to a combination of all these tissue structures working together, because they are significantly interlinked.
... The PVS has great importance in the medical field due to its constituents, including embryonic-like stem cells, hematopoietic stem cells, and immune cells (Islam et al., 2013;Lee et al., 2007;Lee et al., 2014;Lim, Yoon, & Ryu, 2020;Ogay & Soh, 2012). Additionally, the importance of the PVS on hormone transport has been reported. ...
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The primo vascular system (PVS) is observed in different parts of the body under different physiological and disease conditions. Previously, the PVS was not observed in the vagina. The vaginal samples of this study were collected from the female genitalia of healthy New Zealand white rabbits from the animal house, Faculty of Medicine, Assiut University. The vaginal samples were fixed in Bouin's solution. The sections were stained with hematoxylin and eosin and Crossmon's trichrome. Additionally, the sections were immunohistochemically stained with neuron‐specific enolase (NSE) and vascular endothelial growth factor (VEGF). A primo node was observed on the lymph vessel of the vagina and has several characteristics that resemble those of the previously discovered primo nodes. The primo node in this study was surrounded by mesothelial cells that provide positive immunoreactivity to NSE and VEGF. Sinuses of different sizes, floating cells, telocyte‐like cell, and primo microcells were observed as the main constituents of the primo node. Additionally, migratory cells were detected, which passed from the primo node to the enclosing lymph vessel. The current study detected the primo vascular system on the vagina of rabbit. The primo node in this study was surrounded by mesothelial cells that provide positive immunoreactivity to NSE and VEGF. Sinuses of different sizes, floating cells, telocyte‐like cell, and primo microcells were observed as the main constituents of the primo node. Migratory cells were detected, which passed from the primo node to the enclosing lymph vessel.
... However, in 1962, Korean researcher Bong-Han Kim demonstrated the existence of the acupuncture meridian system as a physical entity, which he termed the primo vascular system (PVS; Kim, 1962). In 2009 Korean research confirmed Kim's findings (Soh, 2009), identifying the PVS in various organs, and subsequent research likewise confirmed the existence of the PVS (Lee et al., 2014;Soh, Kang, & Ryu, 2013). Further, Feinstein (2018) postulates that electrical signals are produced by way of "mechanosensory transduction," which is supported by imaging studies showing that electrical energy is discharged via stimulated cells (Bai et al., 2011;Finando & Finando, 2012). ...
Article
Purpose: The aim of this experimental study was to investigate the post-intervention effects of group-based positive psychology and mindful diaphragmatic breathing on anxiety and testtaking success in male college students. Method: A randomized controlled trial (RCT) was conducted across the undergraduate male students at a university in Montana. Participants (aged 18–32 years) were randomly assigned to two intervention groups (mindfulness and positive psychology) and a control (delayed intervention) group. The study included a group of 34 male participants with 10 in the mindfulness group, 12 in the positive psychology group, and 12 in the waiting group. Both intervention programs consisted of five 120-minute group sessions delivered over 10 weeks. All three groups were required to complete an assessment prior to the interventions and a second assessment after the interventions (mindfulness and positive psychology) or the waiting time (control group) were completed. The control group also received five 120-minute interventions after all measurements were taken. The constructs of self-care, test anxiety, and anxiety symptomatology were measured. Results: There were no significant baseline differences between the three groups on the demographic and dependent variables. The results showed no significant differences between the two intervention groups’ and the control group’s self-care pre and post scores. Results showed a significant difference between the treatment groups’ and control group’s scores on pretest and posttest in test anxiety. The results showed a significant difference between the two intervention groups’ and control group’s scores on pretest and posttest in total anxiety. Anxiety levels were noted to be different for ethnic groups. An explanation for observed differences in race is discussed. Conclusion: The study does not provide evidence that mindfulness and positive psychology interventions can reduce test anxietysignificantly. The results show a significant difference between the two intervention groups’ and control group’s scores on pretest and posttest in total anxiety. Importantly, descriptive analysis has shown a positive impact on test anxiety and total anxiety in participants of varied ethnic groups.
... Those structures were reinvestigated approximately 50 years later [35] by other researches including Soh [36], Stefanov and Kim [37], and Stefanov et al [38]. that were able to detected, with new techniques for coloration, corpuscles and ducts in adipose tissue and fascia [39] inside the blood vessels (caudal blood vena of rabbits and rats, abdominal arteries and veins, hepatic vein [40,41], lymphatic vessels of rats [42], human umbilical cord and placenta [43]), in the surface of internal organs [44,45], in the cerebrospinal fluid of brain ventricles [46], and in the spinal cord of rabbits [47] that were identified as being the BHD and Bonghan corpuscle described years ago by Kim Bong-Han. As a result of these new studies, the BHDs were renamed primo vascular vessels (PVs) and the Bonghan nodes (BHN), primo nodes (PNs) [37]. ...
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Acupuncture is one of the areas among the alternative therapies that arise high curiosity in the biomedical scientific community. It is particularly popular for treatment of chronic diseases and addictions. However, contrasting with its evidence-based effectiveness, the lack of reasonable explanations for its mode of action divides that scientific community. Difficulties also arise to those responsible for providing information for clinicians and professionals who wish to acquire competencies leading to the acupuncture practice and have a background based on biochemistry and physiology. The classic theories of nerve conduction do not fully explain how information is read and transmitted during the acupuncture treatment. Other theories have been proposed, but they are based on concepts such as biophotonic waves and quantum biochemistry that are difficult to read and understand by those who do not have knowledge in physics. It is the main objective of this review to provide a summary of the main theories and explanatory approaches to the signal transduction and conduction in acupuncture and to describe them in terms of their explanatory hypotheses, limitations, and weaknesses. The most of the literature found support theories for neural conduction, including gate control. They explain the effects of acupuncture in pain relief; few studies have been conducted concerning the conduction based on biophotons. The primo vascular system has been referred as a possible anatomic support for conduction of information during an acupuncture treatment, which could be connected to biophoton transmission.
... Podoplanin is a transmembrane protein. A membranous reaction is evident in epithelial cells, such as those of mesothelioma, whereas cytoplasmic staining is dominant in spindle cells, such as follicular dendritic cells 5,7,9 . In our study, membranous staining was detected in decidual cells with an epithelioid appearance, and cytoplasmic staining in CVS cells. ...
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Podoplanin, a reliable marker of lymphatic endothelium, is a mucin-type transmembrane protein. Although the human placenta is devoid of a lymphatic system, chorionic villous stromal (CVS) cells express podoplanin. In this study, the pattern of podoplanin expression in normal and pathological placental tissues and the biological role of podoplanin were investigated. In total, 198 placental tissues belonging to 184 patients, seen at the Department of Pathology of Bulent Ecevit University Education and Research Hospital, Zonguldak, Turkey, were evaluated histopathologically and determined to meet the study criteria. The tissues were assigned to control, cisternal placental disorders, inflammation and hypoxic-ischemic pathology groups. Podoplanin expression in CVS cells was graded from 0 to 3 depending on the staining intensity, as determined by an immunohistochemical evaluation of chorionic villi in the most intensively stained tissue region. Podoplanin levels in control CVS cells increased in parallel with placental maturation, whereas in molar pregnancies podoplanin expression was lower than in control tissues. In the acute placental inflammation group, podoplanin immunoreactivity was similar to that in the control group, whereas in the preeclampsia group, podoplanin expression was higher than in all other groups. Our study showed an increase in podoplanin expression in CVS cells during pregnancy. In preeclamptic patients, the increase in podoplanin expression may be a response to hypoxic-ischemic conditions, whereas in molar pregnancies the decrease in podoplanin levels may cause villous swelling by disrupting intercellular fluid homeostasis.
Chapter
The gene expression of Prox-1 and Hif-1a for the isolated primo vessels (PVs) and composite lymphatic vessels (LVs) containing PVs (LVs + PVs) was investigated by RNA-sequencing (Seq) and quantitative polymerase chain reaction (qRT-PCR) analysis. RNA-Seq on the passed 10 samples on RNA-QC for two experimental groups with PVs and PVs + LVs proceeded to the library construction stage automatically and analyzed differentially expressed genes (DEGs). From the real-time qRT-PCR analysis data, we found the marker genes of Prox-1 and Hif-1a were enriched and decreased in an isolated PVs compared to LVs, respectively. Based on mRNA transcriptional data, Prox-1 and Hif-1a were increased and decreased in PVs compared to LVs + PVs under lipopolysaccharide (LPS) treatment and relieved by acupuncture electric stimulation (AES), respectively. This finding indicates that high and low levels of Prox-1 and Hif-1a may be involved in the function of PVs and that pathophysiological and physiological condition could progress into inflamed lymphatic endothelial cells expanding the PV within the LV.
Article
In Parkinson's disease, the dopaminergic neurons of the brain are destroyed. Dopamine is an important neurotransmitter that acts on the basal ganglia of the brain, allowing precise body movement. In the early stages of Parkinson's disease, levodopa appears to alleviate clinical symptoms; however, during long-term use, motor complications occur. There is no clear treatment or remedy for Parkinson's disease; therefore, the development of novel therapies is urgently required. In the present study, mouse choroid plexus cells were transplanted into ST36 in a mouse model of Parkinson's disease to determine whether the motor function could be restored. Pole tests showed changes in motor dysfunction in the mice. The athletic ability of the mice was significantly lowered after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) injection and significantly increased after choroidal neuron cell treatment. Injection of di-alkyl indocarbocyanine (DiI) (as a trace substance) confirmed that the choroid plexus cells injected into acupuncture point ST36 were transferred to the brain. In the Parkinson's disease model, choroid plexus cell injection into ST36 inhibited the decrease in tyrosine hydroxylase (TH) expression and decreased the activation of inflammatory factors mitochondrial cytochrome C oxidase (COX2) and inducible NO synthase (iNOS). Apoptosis factors Cytochrome C and BCL2 associated X, apoptosis regulator (BAX) levels were decreased and B-Cell CLL/Lymphoma 2 (BCL2) levels were increased. Taken together, these results suggest that the injection of choroid plexus cell at ST36 had neuroprotective effects in the Parkinson's disease mouse model. The results suggest new possibilities for the treatment of Parkinson's disease.
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The first International Symposium on Primo Vascular System 2010 (ISPS 2010) with special topics on cancer and regeneration was held in Jecheon, Korea during September 17-18, 2010. The symposium dealt with the past findings, current status, and future prospect of the PVS research in the context of cutting-edge investigation in oriental and occidental medicine, molecular biology, and biophysics. This proceedings volume explores the first international opportunity to exchange the research results on PVS among multi-disciplinary experts. New study results have better revealed the functional aspects of PVS, including its roles in the areas of regenerative medicine and cancer. These research results have also suggested the extensive roles of PVS in humans, potentially changing the entire paradigm of medicine. The Primo Vascular System is a timely volume that will help accelerate many disciplines as it delves into this newly researched system.
Chapter
In the past decade, researchers at Seoul National University of South Korea have validated the existence of the primo-vascular system using animal models, which was originally reported by Bonghan Kim in the 1960s. After exploring a variety of dye stains, Kwang-Sup Soh, et al. found that trypan blue is an effective dye for staining structures of the primo vessels and nodes. Most of the studies reported so far have used relatively large animal models such as rabbits. In this study, we explored the potential of visualizing primo-vascular system in murine models. As compared to conventional models used for primo-vascular studies, murine models are more versatile and affordable. In mice, we found primo ­vessels extended to and from abdominal viscera, often disappearing in layers of adipose tissue before resurfacing in a more distal region. In addition, we found potential primo-vascular structures on the tumor surface. These structures were loosely attached to the surface of the tumor and some segments appear to be within the clear serosal tissue or invading into the tumor. The experience of identifying ­primo-vascular system in rodents empowers us to investigate the detailed relationship of primo-vessels and cancer in future studies. A breakthrough in ­elucidating the complete anatomical and physiological description of the primo-vascular system holds great promise of unraveling the molecular basis of various human diseases.
Article
We report on the observation of a thread-like structure, which is a semi-transparent elastic bundle of tubules, inside the blood vessels of rats and rabbits. We contrived a method using an intravenous injection of a 10 % dextrose solution at the vena femoralis to cause blood to coagulate around an intra-blood-vessel duct (IBVD) so that it became thick and strong. The tubular substructure of the IBVD was observed by using a differential interference contrast image and by using an electrical separation technique. The functions of the IBVD are not known at the present time. We might speculate that the IBVD is a Bonghan duct, which is known to be the only thread-like structure inside blood vessels.
Article
The existence of a hyaluronic acid-rich node and duct system (HAR-NDS) within the lymphatic and blood vessels was demonstrated previously. The HAR-NDS was enriched with small (3.0–5.0 μm in diameter), adult stem cells with properties similar to those of the very small embryonic-like stem cells (VSELs). Sca-1+Lin−CD45− cells were enriched approximately 100-fold in the intravascular HAR-NDS compared with the bone marrow. We named these adult stem cells “node and duct stem cells (NDSCs).” NDSCs formed colonies on C2C12 feeder layers, were positive for fetal alkaline phosphatase, and could be subcultured on the feeder layers. NDSCs were Oct4+Nanog+SSEA-1+Sox2+, while VSELs were Oct4+Nanog+SSEA-1+Sox2−. NDSCs had higher sphere-forming efficiency and proliferative potential than VSELs, and they were found to differentiate into neuronal cells in vitro. Injection of NDSCs into mice partially repaired ischemic brain damage. Thus, we report the discovery of potential adult stem cells that may be involved in tissue regeneration. The intravascular HAR-NDS may serve as a route that delivers these stem cells to their target tissues.
Article
The primo vascular system (PVS), which is composed of very small primo-vessels (PV) and primo-nodes (PN), has recently emerged as a third component of circulatory system. Here, we report the presence of a tumor derived PVS in murine xenografts of human histiocytic lymphoma (U937) in close proximity to the tumor. Within this system, PNs are small (~ 500–600 μM diameter) membranous sac-like structures which contain numerous small cells which can be demonstrated by DAPI staining. Hematoxylin and Eosin (H&E) staining of the peri-tumoral PVS shows the presence of loose structures lined by fibroblasts but filled with dense fibers, cells, lacunae and nerve-like structures. The origin and type of cells within the PVS was characterized by immunostaining with antibodies for CD68, CD45 and lysozyme. The results of these studies reveal that the PVS of the xenograft originates from the human U937 tumor cells. qRT-PCR analysis of mRNA isolated from PVS cells reveals a striking predominance of human, rather than mouse, sequences. Of particular interest, human stem cell specific transcription factors were overexpressed, most notably KLF4, an upstream regulator of NANOG which maintains the pluripotent and undifferentiated state of stem cells. These results suggest that the cells present within the PVS are derived from the human xenograft and suggests that the primo-vessels associated with the xenografted tumor may provide a safe haven for a select population of cancer stem cells. Further understanding of the biological properties of these cells may allow the development of new anti-cancer interventions.