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A new lymphedema treatment using pyro-drive jet injection

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Abstract

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.

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Data availability

The data that support the findings of this study are available from the corresponding authors, SA and MN, upon reasonable request.

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Acknowledgements

We thank M. Nishida, Y. Mine and S. Nishimura for excellent technical assistance. This work was supported by the Analytical Research Center for Experimental Sciences, Saga University.

Funding

This research was supported by Daicel Corporation.

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Authors and Affiliations

  1. Division of Pathology, Department of Pathology and Microbiology, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga, Saga, 849-8501, Japan

    Megumi Nishiyama, Sayuri Morito, Takehisa Sakumoto, Mariko Hashiguchi & Shigehisa Aoki

  2. Medical Device Division Life Sciences SBU, Daicel Corporation, Osaka, Japan

    Yuko Sakaguchi & Kunihiko Yamashita

  3. Department of Urology, Faculty of Medicine, Saga University, Saga, Japan

    Kei Nagase

  4. Division of Nephrology, Department of Internal Medicine, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan

    Makoto Fukuda

  5. Department of Pathology, Takagi Hospital, 141-11 Sakemi, Okawa, Fukuoka, 831-0016, Japan

    Shuji Toda

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  1. Megumi Nishiyama
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Correspondence to Shigehisa Aoki.

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Conflict of interest

Y. Sakaguchi and K. Yamashita are employees of Daicel Corporation.; S. Aoki received a research grant from Daicel Corporation. The sponsor had no control over the interpretation, writing, or publication of this work. Other authors have no competing interests to disclose. A patent application related to the content of this research has been filed in Japan.

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13577_2023_1021_MOESM1_ESM.pdf

Supplementary file1 Characteristics when the proportion of liquid components was increased relative to the proportion of air components. A Gross appearance of rat skin tissue after PJI (30). In this experimental group, larger bulges (arrowheads) appear compared to the group injected with 10 µL of lactated Ringer's solution and 40 µL of gas. B Arrows indicate the formation of representative clefts between collagen fibers in the dermis associated with PJI (30). In this experimental group, the number of spherical clefs decreases compared to the group injected with 10 µL of lactated Ringer's solution and 40 µL of gas. C Representative macroscopic temporal images of experimental lymphedema. D Relative reduction rate of soft tissue. In this study, we observed no significant differences among the three groups. This graph compares the data among the Control group (n = 6), PJI3 group (n = 5), and PJI5 group (n = 5) (PDF 3659 KB)

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Nishiyama, M., Sakaguchi, Y., Morito, S. et al. A new lymphedema treatment using pyro-drive jet injection. Human Cell 37, 465–477 (2024). https://doi.org/10.1007/s13577-023-01021-2

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