A new lymphedema treatment using pyro-drive jet injection.
Angiogenesis
Connective tissue growth factor
Granulation tissue
Injection therapy
Lymphedema
Vascular endothelial growth factor
Journal
Human cell
ISSN: 1749-0774
Titre abrégé: Hum Cell
Pays: Japan
ID NLM: 8912329
Informations de publication
Date de publication:
14 Jan 2024
14 Jan 2024
Historique:
received:
09
10
2023
accepted:
07
12
2023
medline:
14
1
2024
pubmed:
14
1
2024
entrez:
13
1
2024
Statut:
aheadofprint
Résumé
Lymphedema, resulting from impaired lymphatic drainage, causes inflammation, fibrosis and tissue damage leading to symptoms such as limb swelling and restricted mobility. Despite various treatments under exploration, no standard effective therapy exists. Here a novel technique using the pyro-drive jet injection (PJI) was used to create artificial clefts between collagen fibers, which facilitated the removal of excess interstitial fluid. The PJI was used to deliver a mixture of lactated Ringer's solution and air into the tail of animals with secondary skin edema. Edema levels were assessed using micro-CT scanning. Histopathological changes and neovascularization were evaluated on the injury-induced regenerative tissue. Regarding tissue remodeling, we focused on connective tissue growth factor (CTGF) and vascular endothelial growth factor (VEGF)-C. PJI markedly diminished soft tissue volume in the experimental lymphedema animals compared to the non-injected counterparts. The PJI groups exhibited a significantly reduced proportion of inflammatory granulation tissue and an enhanced density of lymphatic vessels and α-smooth muscle actin (αSMA)-positive small vessels in the fibrous granulation tissue compared to the controls. In addition, PJI curtailed the prevalence of CTGF- and VEGF-C-positive cells in regenerative tissue. In a lymphedema animal model, PJI notably ameliorated interstitial edema, promoted lymphatic vessel growth, and bolstered αSMA-positive capillaries in fibrous granulation tissue. PJI's minimal tissue impact post-lymph node dissection indicates significant potential as an early, standard preventative measure. Easily applied in general clinics without requiring specialized training, it offers a cost-effective and highly versatile solution to the management of lymphedema.
Identifiants
pubmed: 38218753
doi: 10.1007/s13577-023-01021-2
pii: 10.1007/s13577-023-01021-2
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024. The Author(s) under exclusive licence to Japan Human Cell Society.
Références
Kumar V, Abbas AK, Aster JC, Elsevier C. Robbins & Cotran pathologic basis of disease. Tenth edition ed. Robbins pathology. Amsterdam: Elsevier; 2020.
Grada AA, Phillips TJ. Lymphedema: pathophysiology and clinical manifestations. J Am Acad Dermatol. 2017;77(6):1009–20.
doi: 10.1016/j.jaad.2017.03.022
pubmed: 29132848
Mortimer PS. The pathophysiology of lymphedema. Cancer. 1998;83(S12B):2798–802.
doi: 10.1002/(SICI)1097-0142(19981215)83:12B+<2798::AID-CNCR28>3.0.CO;2-E
pubmed: 9874400
Maclellan RA, Couto RA, Sullivan JE, Grant FD, Slavin SA, Greene AK. Management of primary and secondary lymphedema: analysis of 225 referrals to a center. Ann Plast Surg. 2015;75(2):197–200.
doi: 10.1097/SAP.0000000000000022
pubmed: 24691335
Lasinski BB, Thrift KM, Squire D, Austin MK, Smith KM, Wanchai A, et al. A systematic review of the evidence for complete decongestive therapy in the treatment of lymphedema from 2004 to 2011. PM&R. 2012;4(8):580–601.
doi: 10.1016/j.pmrj.2012.05.003
Mondry TE, Riffenburgh RH, Johnstone PA. Prospective trial of complete decongestive therapy for upper extremity lymphedema after breast cancer therapy. Cancer J. 2004;10(1):42–8.
doi: 10.1097/00130404-200401000-00009
pubmed: 15000494
Nagase T, Gonda K, Inoue K, Higashino T, Fukuda N, Gorai K, et al. Treatment of lymphedema with lymphaticovenular anastomoses. Int J Clin Oncol. 2005;10:304–10.
doi: 10.1007/s10147-005-0518-5
pubmed: 16247656
Koshima I, Inagawa K, Urushibara K, Moriguchi T. Supermicrosurgical lymphaticovenular anastomosis for the treatment of lymphedema in the upper extremities. J Reconstr Microsurg. 2000;16(06):437–42.
doi: 10.1055/s-2006-947150
pubmed: 10993089
Saaristo AM, Niemi TS, Viitanen TP, Tervala TV, Hartiala P, Suominen EA. Microvascular breast reconstruction and lymph node transfer for postmastectomy lymphedema patients. Ann Surg. 2012;255(3):468–73.
doi: 10.1097/SLA.0b013e3182426757
pubmed: 22233832
Patel KM, Lin C-Y, Cheng M-H. A prospective evaluation of lymphedema-specific quality-of-life outcomes following vascularized lymph node transfer. Ann Surg Oncol. 2015;22:2424–30.
doi: 10.1245/s10434-014-4276-3
pubmed: 25515196
Miyazaki H, Atobe S, Suzuki T, Iga H, Terai K. Development of pyro-drive jet injector with controllable jet pressure. J Pharm Sci. 2019;108(7):2415–20. https://doi.org/10.1016/j.xphs.2019.02.021 .
doi: 10.1016/j.xphs.2019.02.021
pubmed: 30849461
Chang C, Sun J, Hayashi H, Suzuki A, Sakaguchi Y, Miyazaki H, et al. Stable immune response induced by intradermal DNA Vaccination by a novel needleless pyro-drive jet injector. AAPS PharmSciTech. 2019;21(1):19. https://doi.org/10.1208/s12249-019-1564-z .
doi: 10.1208/s12249-019-1564-z
pubmed: 31820256
Serizawa F, Ito K, Matsubara M, Sato A, Shimokawa H, Satomi S. Extracorporeal shock wave therapy induces therapeutic lymphangiogenesis in a rat model of secondary lymphoedema. Eur J Vasc Endovasc Surg. 2011;42(2):254–60. https://doi.org/10.1016/j.ejvs.2011.02.029 .
doi: 10.1016/j.ejvs.2011.02.029
pubmed: 21454105
Desmoulière A, Chaponnier C, Gabbiani G. Tissue repair, contraction, and the myofibroblast. Wound Repair Regen. 2005;13(1):7–12.
doi: 10.1111/j.1067-1927.2005.130102.x
pubmed: 15659031
Mescher AL, Junqueira LCU. Junqueira’s basic histology: text and atlas. Sixteenth. New York: McGraw-Hill; 2021.
Armulik A, Abramsson A, Betsholtz C. Endothelial/pericyte interactions. Circ Res. 2005;97(6):512–23.
doi: 10.1161/01.RES.0000182903.16652.d7
pubmed: 16166562
Pak KH, Park KC, Cheong J-H. VEGF-C induced by TGF-β1 signaling in gastric cancer enhances tumor-induced lymphangiogenesis. BMC Cancer. 2019;19:1–9.
doi: 10.1186/s12885-019-5972-y
Ihn H. Pathogenesis of fibrosis: role of TGF-β and CTGF. Curr Opin Rheumatol. 2002;14(6):681–5.
doi: 10.1097/00002281-200211000-00009
pubmed: 12410091
Leask A, Holmes A, Abraham DJ. Connective tissue growth factor: a new and important player in the pathogenesis of fibrosis. Curr Rheumatol Rep. 2002;4(2):136–42.
doi: 10.1007/s11926-002-0009-x
pubmed: 11890879
Shi-Wen X, Leask A, Abraham D. Regulation and function of connective tissue growth factor/CCN2 in tissue repair, scarring and fibrosis. Cytokine Growth Factor Rev. 2008;19(2):133–44.
doi: 10.1016/j.cytogfr.2008.01.002
pubmed: 18358427
Alitalo K, Tammela T, Petrova TV. Lymphangiogenesis in development and human disease. Nature. 2005;438(7070):946–53.
doi: 10.1038/nature04480
pubmed: 16355212
Cueni LN, Detmar M. New insights into the molecular control of the lymphatic vascular system and its role in disease. J Investig Dermatol. 2006;126(10):2167–77.
doi: 10.1038/sj.jid.5700464
pubmed: 16983326
Ramanujan S, Pluen A, McKee TD, Brown EB, Boucher Y, Jain RK. Diffusion and convection in collagen gels: implications for transport in the tumor interstitium. Biophys J. 2002;83(3):1650–60.
doi: 10.1016/S0006-3495(02)73933-7
pubmed: 12202388
pmcid: 1302261
Goldman J, Conley KA, Raehl A, Bondy DM, Pytowski B, Swartz MA, et al. Regulation of lymphatic capillary regeneration by interstitial flow in skin. Am J Physiol Heart Circ Physiol. 2007;292(5):H2176–83. https://doi.org/10.1152/ajpheart.01011.2006 .
doi: 10.1152/ajpheart.01011.2006
pubmed: 17189348
Ongstad EL, Bouta EM, Roberts JE, Uzarski JS, Gibbs SE, Sabel MS, et al. Lymphangiogenesis-independent resolution of experimental edema. Am J Physiol Heart Circ Physiol. 2010;299(1):H46-54. https://doi.org/10.1152/ajpheart.00008.2010 .
doi: 10.1152/ajpheart.00008.2010
pubmed: 20207821
pmcid: 2904140
Kim S, Chung M, Ahn J, Lee S, Jeon NL. Interstitial flow regulates the angiogenic response and phenotype of endothelial cells in a 3D culture model. Lab Chip. 2016;16(21):4189–99.
doi: 10.1039/C6LC00910G
pubmed: 27722679
Swartz MA, Fleury ME. Interstitial flow and its effects in soft tissues. Annu Rev Biomed Eng. 2007;9:229–56.
doi: 10.1146/annurev.bioeng.9.060906.151850
pubmed: 17459001
Avraham T, Daluvoy S, Zampell J, Yan A, Haviv YS, Rockson SG, Mehrara BJ. Blockade of transforming growth factor-β1 accelerates lymphatic regeneration during wound repair. Am J Pathol. 2010;177(6):3202–14. https://doi.org/10.2353/ajpath.2010.100594 .
doi: 10.2353/ajpath.2010.100594
pubmed: 21056998
pmcid: 2993295
Clavin NW, Avraham T, Fernandez J, Daluvoy SV, Soares MA, Chaudhry A, Mehrara BJ. TGF-β1 is a negative regulator of lymphatic regeneration during wound repair. Am J Physiol-Heart Circ Physiol. 2008;295(5):H2113–27.
doi: 10.1152/ajpheart.00879.2008
pubmed: 18849330
Kinashi H, Ito Y, Sun T, Katsuno T, Takei Y. Roles of the TGF-β–VEGF-C pathway in fibrosis-related lymphangiogenesis. Int J Mol Sci. 2018;19(9):2487.
doi: 10.3390/ijms19092487
pubmed: 30142879
pmcid: 6163754
Baik JE, Park HJ, Kataru RP, Savetsky IL, Ly CL, Shin J, et al. TGF-β1 mediates pathologic changes of secondary lymphedema by promoting fibrosis and inflammation. Clin Transl Med. 2022;12(6): e758.
doi: 10.1002/ctm2.758
pubmed: 35652284
pmcid: 9160979
Zimmermann A, Wozniewski M, Szklarska A, Lipowicz A, Szuba A. Efficacy of manual lymphatic drainage in preventing secondary lymphedema after breast cancer surgery. Lymphology. 2012;45(3):103–12.
pubmed: 23342930
Finnane A, Janda M, Hayes SC. Review of the evidence of lymphedema treatment effect. Am J Phys Med Rehabil. 2015;94(6):483–98.
doi: 10.1097/PHM.0000000000000246
pubmed: 25741621
Uzkeser H, Karatay S, Erdemci B, Koc M, Senel K. Efficacy of manual lymphatic drainage and intermittent pneumatic compression pump use in the treatment of lymphedema after mastectomy: a randomized controlled trial. Breast Cancer. 2015;22:300–7.
doi: 10.1007/s12282-013-0481-3
pubmed: 23925581
Boccardo F, Casabona F, De Cian F, Friedman D, Villa G, Bogliolo S, et al. Lymphedema microsurgical preventive healing approach: a new technique for primary prevention of arm lymphedema after mastectomy. Ann Surg Oncol. 2009;16:703–8.
doi: 10.1245/s10434-008-0270-y
pubmed: 19139964
Campisi C, Bellini C, Campisi C, Accogli S, Bonioli E, Boccardo F. Microsurgery for lymphedema: clinical research and long-term results. Microsurgery. 2010;30(4):256–60.
doi: 10.1002/micr.20737
pubmed: 20235160
Balzarini A, Pirovano C, Diazzi G, Olivieri R, Ferla F, Galperti G, et al. Ultrasound therapy of chronic arm lymphedema after surgical treatment of breast cancer. Lymphology. 1993;26(3):128–34.
pubmed: 8258986
Brorson H. Liposuction in arm lymphedema treatment. Scand J Surg. 2003;92(4):287–95.
doi: 10.1177/145749690309200409
pubmed: 14758919
Brorson H. Liposuction in lymphedema treatment. J Reconstr Microsurg. 2016;32(01):056–65.
Brorson H, Svensson H. Liposuction combined with controlled compression therapy reduces arm lymphedema more effectively than controlled compression therapy alone. Plast Reconstr Surg. 1998;102(4):1058–67.
doi: 10.1097/00006534-199809020-00021
pubmed: 9734424
Schaverien MV, Munnoch DA, Brorson H. Liposuction Treatment of Lymphedema. Semin Plast Surg. 2018;32(1):42–7. https://doi.org/10.1055/s-0038-1635116 .
doi: 10.1055/s-0038-1635116
pubmed: 29636653
pmcid: 5891650