Potential Mechanisms of Interior Lymphatic Vessel Primo Vessels in Tissue Repair

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Jared M Hall Nicholas E Yates Philip Bauer Gustavo Perez-Abadia Claudio Maldonado


The Primo Vascular System was discovered by Bong Han Kim in the 1960s when searching for an anatomical correlate of the acupuncture meridians used in eastern medicine. The Primo Vascular System is a systemic network of thread-like Primo-vessels with intermittent enlargements known as Primo-nodes. Primo-vessels are difficult to view under a microscope due to their small diameters (20-50 µm) and translucent appearance. Primo-vessels have a porous outer membrane that encapsulates small channels named Primo sub-vessels filled with flowing fluid. Primo-vessels are classified into six sub-types based on their anatomical location. The physiological mechanisms of Primo-vessel function are not clear. There are multiple hypotheses based on Primo-vessel and Primo-node structure and cell content, however, supportive functional experimental data is lacking. This review focuses on the "interior" lymphatic vessel Primo-vessel (ILVPV) sub-type, the techniques that are used to visualize them, and experimental studies that attempt to unravel their physiological role after inflammatory stimulation. Speculative hypotheses are presented regarding the handling of signals by ILVPVs for intercellular communication between injured cells and cells stored within "interior" lymphatic vessel Primo-nodes (ILVPNs). One of the stored cell types that are of interest for tissue repair are very small embryonic-like cells. Very small embryonic-like cell activation may be induced by biophoton signals emitted by injured cells and transmitted to ILVPNs via Primo-vessel and/or ILVPV networks. An alternative or additional method for intercellular communication may involve the release of signaling proteins and/or extravesicular bodies carrying genetic messages (i.e., exosomes) by cells in injured tissues. As these signaling factors enter the lymphatic circulation, porous ILVPVs filter them out and transport them to ILVPNs where they initiate very small embryonic-like cell activation to start the tissue regenerative process. Primo Vascular System research will require more physiological functional studies to elucidate the role of ILVPVs and ILVPNs in tissue regeneration. To achieve this goal, future mechanistic studies will need novel biomarkers and animal models.

Keywords: Primo Vascular System, interior lymphatic primo vessels, exosomes, stem cells, biophoton

Article Details

How to Cite
HALL, Jared M et al. Potential Mechanisms of Interior Lymphatic Vessel Primo Vessels in Tissue Repair. Medical Research Archives, [S.l.], v. 10, n. 12, dec. 2022. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/3438>. Date accessed: 17 june 2024. doi: https://doi.org/10.18103/mra.v10i12.3438.
Research Articles


1. Kim BH. Kyungrak System and Theory of Sanal. Proceedings of the Academic of Kyungrak of DPRK. Medical Science Press, Pyung Yang, DPR Korea, 1965 No.2.
2. Kim BH. Great Discovery in Biology and Medicine - Substances of Kyungrak -. Foreign Language Publishing House. 1962. URL: http://ispvs.org/server/PublicationsArchives/Report-1.pdf
3. Kim BH. On the Kyungrak system. 1964. http://ispvs.org/server/PublicationsArchives/Report-2.pdf
4. Soh KS, Kang KA, Harrison DK. The Primo Vascular System: Its Role in Cancer and Regeneration. Springer New York; 2011.
5. Lee BC, Soh KS. Contrast-enhancing optical method to observe a Bonghan duct floating inside a lymph vessel of a rabbit. Lymphology. Dec 2008;41(4):178-85.
6. Lee BS, Lee BC, Park JE, Choi HK, Choi SJ, Soh KS. Primo vascular system in human umbilical cord and placenta. J Acupunct Meridian Stud. Dec 2014;7(6):291-7. doi:10.1016/j.jams.2014.09.002
7. Park SY, Jung SJ, Bae KH, Soh KS. Protocol for Detecting the Primo Vascular System in the Lymph Ducts of Mice. J Acupunct Meridian Stud. Dec 2015;8(6):321-8. doi:10.1016/j.jams.2015.03.008
8. Johng HM, Yoo JS, Yoon TJ, et al. Use of magnetic nanoparticles to visualize threadlike structures inside lymphatic vessels of rats. Evid Based Complement Alternat Med. Mar 2007;4(1):77-82. doi:10.1093/ecam/nel057
9. Lee BC, Yoo JS, Baik KY, Kim KW, Soh KS. Novel threadlike structures (Bonghan ducts) inside lymphatic vessels of rabbits visualized with a Janus Green B staining method. Anat Rec B New Anat. Sep 2005;286(1):1-7. doi:10.1002/ar.b.20076
10. Ogay V, Bae KH, Kim KW, Soh KS. Comparison of the characteristic features of Bonghan ducts, blood and lymphatic capillaries. J Acupunct Meridian Stud. Jun 2009;2(2):107-17. doi:10.1016/S2005-2901(09)60042-X
11. Lee SJ, Park SH, Kim YI, et al. Adult stem cells from the hyaluronic acid-rich node and duct system differentiate into neuronal cells and repair brain injury. Stem Cells Dev. Dec 1 2014;23(23):2831-40. doi:10.1089/scd.2014.0142
12. Ogay V. Identification and characterization of small stem-like cells in the primo vascular system of adult animals. 2012;In: The Primo Vascular System: Its Role in Cancer and Regeneration (Soh KS, Kang KA, Harrison DH eds.).
13. Hwang S, Lee SJ, Park SH, et al. Nonmarrow hematopoiesis occurs in a hyaluronic-acid-rich node and duct system in mice. Stem Cells Dev. Nov 1 2014;23(21):2661-71. doi:10.1089/scd.2014.0075
14. Kang KA, Pustovyy O, Globa L, Sorokulova I, Vodyanoy V. Sanal-Cell Cycle and Primo Vascular System: Regeneration via Sanals. Adv Exp Med Biol. 2018;1072:413-418. doi:10.1007/978-3-319-91287-5_66
15. Lee HR, Rho MS, Hong YJ, et al. Primo Vessel Stressed by Lipopolysaccharide in Rabbits. J Acupunct Meridian Stud. Dec 2015;8(6):301-6. doi:10.1016/j.jams.2015.05.005
16. Sung B, Kim MS, Lee BC, et al. Measurement of flow speed in the channels of novel threadlike structures on the surfaces of mammalian organs. Naturwissenschaften. Feb 2008;95(2):117-24. doi:10.1007/s00114-007-0300-9
17. Ghiron C. The Primo Vascular System as a Possible Exosomal Route Across the Body: Implications for Tumor Proliferation and Metastasis. J Acupunct Meridian Stud. Feb 2019;12(1):25-28. doi:10.1016/j.jams.2018.06.006
18. Chikly B, Roberts P, Quaghebeur J. Primo Vascular System: A Unique Biological System Shifting a Medical Paradigm. J Am Osteopath Assoc. Jan 2016;116(1):12-21. doi:10.7556/jaoa.2016.002
19. Carlson E, Perez-Abadia G, Adams S, Zhang JZ, Kang KA, Maldonado C. A Novel Technique for Visualizing the Intralymphatic Primo Vascular System by Using Hollow Gold Nanospheres. J Acupunct Meridian Stud. Dec 2015;8(6):294-300. doi:10.1016/j.jams.2015.09.003
20. Lim CJ, Lee SY, Ryu PD. Identification of Primo-Vascular System in Abdominal Subcutaneous Tissue Layer of Rats. Evid Based Complement Alternat Med. 2015;2015:751937. doi:10.1155/2015/751937
21. Nam M-hCS-H, Soh Kwang-Sup. Light and Primo Vascular System in the Brain. Journal of the Korean Physical Society. 2012;60(6):903-906. doi:10.3938/jkps.60.903
22. Han HJ, Kim HB, Cha J, et al. Primo vessel as a novel cancer cell migration path from testis with nanoparticle-labeled and GFP expressing cancer cells. J Acupunct Meridian Stud. Dec 2013;6(6):298-305. doi:10.1016/j.jams.2013.09.003
23. Lee S, Ryu Y, Cha J, et al. Primo vessel inside a lymph vessel emerging from a cancer tissue. J Acupunct Meridian Stud. Oct 2012;5(5):206-9. doi:10.1016/j.jams.2012.07.003
24. Yoo JS, Ayati MH, Kim HB, Zhang WB, Soh KS. Characterization of the primo-vascular system in the abdominal cavity of lung cancer mouse model and its differences from the lymphatic system. PLoS One. Apr 1 2010;5(4):e9940. doi:10.1371/journal.pone.0009940
25. Jung SJ, Bae KH, Nam MH, Kwon HM, Song YK, Soh KS. Primo vascular system floating in lymph ducts of rats. J Acupunct Meridian Stud. Dec 2013;6(6):306-18. doi:10.1016/j.jams.2013.09.001
26. Jung SJ, Gil H, Kim DH, Kim HL, Kim S, Soh KS. Ultrastructure of a Mobile Threadlike Tissue Floating in a Lymph Vessel. Evid Based Complement Alternat Med. 2016;2016:3064072. doi:10.1155/2016/3064072
27. Kim DU, Han JW, Jung SJ, et al. Comparison of Alcian Blue, Trypan Blue, and Toluidine Blue for Visualization of the Primo Vascular System Floating in Lymph Ducts. Evid Based Complement Alternat Med. 2015;2015:725989. doi:10.1155/2015/725989
28. Park DY, Lee HR, Rho MS, Lee SS. Effective isolation of primo vessels in lymph using sound- and ultrasonic-wave stimulation. J Acupunct Meridian Stud. Dec 2014;7(6):298-305. doi:10.1016/j.jams.2014.05.002
29. Park SY, Chang BS, Lee SH, Yoon JH, Kim S, Soh KS. Observation of the Primo Vessel Approaching the Axillary Lymph Node with the Fluorescent Dye, DiI. Evid Based Complement Alternat Med. 2014;2014:287063. doi:10.1155/2014/287063
30. Jung SJ, Cho SY, Bae KH, et al. Protocol for the observation of the primo vascular system in the lymph vessels of rabbits. J Acupunct Meridian Stud. Oct 2012;5(5):234-40. doi:10.1016/j.jams.2012.07.007
31. Jung SJ, Lee SH, Bae KH, Kwon HM, Song YK, Soh KS. Visualization of the primo vascular system afloat in a lymph duct. J Acupunct Meridian Stud. Dec 2014;7(6):337-45. doi:10.1016/j.jams.2014.09.001
32. Kwon BS, Ha CM, Yu S, Lee BC, Ro JY, Hwang S. Microscopic nodes and ducts inside lymphatics and on the surface of internal organs are rich in granulocytes and secretory granules. Cytokine. Nov 2012;60(2):587-92. doi:10.1016/j.cyto.2012.07.016
33. Lee C, Seol SK, Lee BC, Hong YK, Je JH, Soh KS. Alcian blue staining method to visualize bonghan threads inside large caliber lymphatic vessels and x-ray microtomography to reveal their microchannels. Lymphat Res Biol. 2006;4(4):181-90. doi:10.1089/lrb.2006.4402
34. Kim J, Kim DH, Jung SJ, et al. Monitoring the primo vascular system in lymphatic vessels by using window chambers. Biomed Opt Express. Apr 1 2016;7(4):1251-9. doi:10.1364/BOE.7.001251
35. Lim J, Lee S, Su Z, et al. Primo vascular system accompanying a blood vessel from tumor tissue and a method to distinguish it from the blood or the lymph system. Evid Based Complement Alternat Med. 2013;2013:949245. 949245. doi:10.1155/2013/949245
36. Shin JY, Ji JO, Choi DW, et al. Expression of Genes in Primo Vasculature Floating in Lymphatic Endothelium Under Lipopolysaccharide and Acupuncture Electric Stimulation. J Acupunct Meridian Stud. Feb 2019;12(1):3-10. doi:10.1016/j.jams.2018.03.003
37. Shin JY, Choi SH, Choi DW, et al. Differential Gene Expression by RNA-Seq Analysis of the Primo Vessel in the Rabbit Lymph. J Acupunct Meridian Stud. Feb 2019;12(1):11-19. doi:10.1016/j.jams.2018.10.008
38. Zhang L, Oh SW. Production and Characterization of Monoclonal Antibodies Against Primo Vascular System of Rat. J Acupunct Meridian Stud. Jun 2020;13(3):110-115. doi:10.1016/j.jams.2020.05.001
39. Choi C-J, Jung JH, Soh K-S, Ryu YH, Ryu PD, Park S-H. Spontaneous Action Potential from Threadlike Structures on the Surfaces of Abdominal Organs. Journal of the Korean Physical Society. 04/15/2011 2011;58(4):831-836. doi:10.3938/jkps.58.831
40. Choi BK, Hwang SH, Kim YI, Singh R, Kwon BS. The hyaluronic acid-rich node and duct system is a structure organized for innate immunity and mediates the local inflammation. Cytokine. Jan 2019;113:74-82. doi:10.1016/j.cyto.2018.06.011
41. Shin JY, Ji JO, Choi SH, et al. Analysis and Differential Expression of Primo Genes Using RNA-Seq and qRT-PCR Experiments. Adv Exp Med Biol. 2020;1232:393-399. doi:10.1007/978-3-030-34461-0_50
42. Shin JY, Choi JG, Shin S, Yeo S, Lee SS. Gene Expression of Prox-1 and Hif-1a in Primo Vessels Inside Lymph Vessels of the Rabbit. Adv Exp Med Biol. 2021;1269:387-391. doi:10.1007/978-3-030-48238-1_61
43. Choi SH, Choi JG, Lee SS. Injection Effect of Anti-CD3 Monoclonal Antibody on Primo Vessel in Lymph Vessel of Rabbit with Lipopolysaccharide-Induced Inflammation. J Acupunct Meridian Stud. Feb 28 2022;15(1):37-42. doi:10.51507/j.jams.2022.15.1.37
44. Soh KS. Bonghan Duct and Acupuncture Meridian as Optical Channel of Biophoton. Journal of the Korean Physical Society. 2004;45(5):1196-1198.
45. Kumar S, Boone K, Tuszynski J, Barclay P, Simon C. Possible existence of optical communication channels in the brain. Sci Rep. Nov 7 2016;6:36508. doi:10.1038/srep36508
46. Popp FA. Properties of biophotons and their theoretical implications. Indian J Exp Biol. May 2003;41(5):391-402.
47. Le M, McNeill FE, Seymour C, Rainbow AJ, Mothersill CE. An observed effect of ultraviolet radiation emitted from beta-irradiated HaCaT cells upon non-beta-irradiated bystander cells. Radiat Res. Mar 2015;183(3):279-90. doi:10.1667/RR13827.1
48. Fels D. Cellular communication through light. PLoS One. 2009;4(4):e5086. doi:10.1371/journal.pone.0005086
49. Tang R, Dai J. Spatiotemporal imaging of glutamate-induced biophotonic activities and transmission in neural circuits. PLoS One. 2014;9(1):e85643. doi:10.1371/journal.pone.0085643
50. Salari V, Scholkmann F, Bokkon I, Shahbazi F, Tuszynski J. The Physical Mechanism for Retinal Discrete Dark Noise: Thermal Activation or Cellular Ultraweak Photon Emission? PLoS One. 2016;11(3):e0148336. doi:10.1371/journal.pone.0148336
51. kesson T, Albrow MG, Almehed S, et al. Comparison of low-PT photon production in high- and low-multiplicity collisions at the CERN ISR. Phys Rev D Part Fields. Nov 1 1988;38(9):2687-2694.
52. Popp FA, Nagl W, Li KH, Scholz W, Weingärtner O, Wolf R. Biophoton emission. New evidence for coherence and DNA as source. Cell Biophys. 1984/03// 1984;6(1):33-52. doi:10.1007/bf02788579
53. Lo Cicero A, Delevoye C, Gilles-Marsens F, et al. Exosomes released by keratinocytes modulate melanocyte pigmentation. Nat Commun. Jun 24 2015;6:7506. doi:10.1038/ncomms8506
54. Al-Mayah A, Bright S, Chapman K, et al. The non-targeted effects of radiation are perpetuated by exosomes. Mutat Res. Feb 2015;772:38-45. doi:10.1016/j.mrfmmm.2014.12.007
55. Xu S, Wang J, Ding N, et al. Exosome-mediated microRNA transfer plays a role in radiation-induced bystander effect. RNA Biol. 2015;12(12):1355-63. doi:10.1080/15476286.2015.1100795
56. Le M, Fernandez-Palomo C, McNeill FE, Seymour CB, Rainbow AJ, Mothersill CE. Exosomes are released by bystander cells exposed to radiation-induced biophoton signals: Reconciling the mechanisms mediating the bystander effect. PLoS One. 2017;12(3):e0173685. doi:10.1371/journal.pone.0173685