Short term treatment of secondary lymphedema with hyaluronidase injections reduces mouse hindlimb lymphedema

Farima Dalaei; Amar Bucan; Alexander Wiinholt; Mads Gustaf Jørgensen; Christian Rønn Hansen; Christina Baun; Svend Hvidsten; Eva Kildall  Hejbøl; Henrik Daa  Schrøder; Jens Ahm Sørensen

doi:10.2340/jphs.v58.7791

Authors

Farima Dalaei Research Unit of Plastic Surgery, Department of Plastic Surgery, Odense University Hospital, Odense, Denmark; Clinical Institute, University of Southern Denmark, Odense, Denmark https://orcid.org/0000-0003-2305-7758
Amar Bucan Research Unit of Plastic Surgery, Department of Plastic Surgery, Odense University Hospital, Odense, Denmark; Clinical Institute, University of Southern Denmark, Odense, Denmark https://orcid.org/0000-0003-2775-8463
Alexander Wiinholt Research Unit of Plastic Surgery, Department of Plastic Surgery, Odense University Hospital, Odense, Denmark; Clinical Institute, University of Southern Denmark, Odense, Denmark https://orcid.org/0000-0003-4760-3549
Mads Gustaf Jørgensen Research Unit of Plastic Surgery, Department of Plastic Surgery, Odense University Hospital, Odense, Denmark; Clinical Institute, University of Southern Denmark, Odense, Denmark https://orcid.org/0000-0002-8755-3446
Christian Rønn Hansen Laboratory of Radiation Physics, Odense University Hospital, Odense, Denmark; Institute of Clinical Research, University of Southern Denmark, Odense, Denmark https://orcid.org/0000-0001-5716-6069
Christina Baun Institute of Clinical Research, University of Southern Denmark, Odense, Denmark; Department of Nuclear Medicine, Odense University Hospital, Odense, Denmark https://orcid.org/0000-0002-5199-9200
Svend Hvidsten Institute of Clinical Research, University of Southern Denmark, Odense, Denmark; Department of Nuclear Medicine, Odense University Hospital, Odense, Denmark https://orcid.org/0000-0002-8857-4521
Eva Kildall Hejbøl Institute of Clinical Research, University of Southern Denmark, Odense, Denmark; Department of Pathology, Odense University Hospital, Odense, Denmark https://orcid.org/0000-0002-3462-321X
Henrik Daa Schrøder Institute of Clinical Research, University of Southern Denmark, Odense, Denmark; Department of Pathology, Odense University Hospital, Odense, Denmark https://orcid.org/0000-0001-7588-235X
Jens Ahm Sørensen Research Unit of Plastic Surgery, Department of Plastic Surgery, Odense University Hospital, Odense, Denmark; Clinical Institute, University of Southern Denmark, Odense, Denmark https://orcid.org/0000-0003-4903-0094

DOI:

https://doi.org/10.2340/jphs.v58.7791

Keywords:

Secondary Lymphedema, hyaluronidase, hyalase, HYAL, treatment of secondary lymphedema, treatment of lymphedema, animal model

Abstract

Lymphedema is a common complication following breast cancer treatment with axillary lymphadenectomy and radiotherapy. Currently, there is no curative treatment for this disease, hence there is a need for new therapeutic suggestions. The aim of this study was to investigate the effect of hyaluronidase (HYAL) injections after inducing hindlimb lymphedema in 36 female C57BL/6 mice. HYAL injections were administered every second day for 14 days in three groups: (1) HYAL for 1 week followed by saline for 1 week, (2) HYAL for 2 weeks, and (3) saline injections for 2 weeks. Volume of the lymphedema limb was weekly assessed with micro-computed tomography (μ-CT) scans for a total course of 6 weeks. Lymph vessel morphometry was assessed in the end of the study after staining cross-sections of the hindlimb for anti-LYVE-1 blindly. Lymphatic function was assessed by lymphoscintigraphy to assess lymphatic clearance. There was a significant reduction of the volume of lymphedema in mice treated with HYAL-7 compared with mice treated with HYAL-14 (p < 0.05) and saline (p < 0.05). No differences were detected in lymph vessel morphometry and the lymphoscintigraphy between groups. Short-term treatment with HYAL-7 might be a potential therapeutic suggestion for secondary lymphedema induced in mouse hindlimbs. In the future, clinical studies are needed to investigate the potential of HYAL treatment in human beings.

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