Adipose-derived regenerative cells and fat grafting for treating breast cancer-related lymphedema: Lymphoscintigraphic evaluation with 1 year of follow-up

Toyserkani, Navid Mohamadpour; Jensen, Charlotte Harken; Tabatabaeifar, Siavosh; Jørgensen, Mads Gustaf; Hvidsten, Svend; Simonsen, Jørn; Andersen, Ditte Caroline; Sheikh, Saifuddin; Sørensen, Jens Ahm

doi:10.1016/j.bjps.2018.09.007

Cited by 26 publications

(37 citation statements)

References 22 publications

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“…Interventions included lymph node or vessel transfer (3 of 5 articles) [3,6,9], complex decongestive therapy (CDT) (1 of 5) [10], and adipose-derived stem cell (ADSC) injection (1 of 5) [7]. In most studies, lymphoscintigraphy was performed before and after treatment [3,[6][7]9]. However, in one study, lymphoscintigraphy was performed only before treatment, with the aim of predicting clinical response to CDT [10].…”

Section: Resultsmentioning

confidence: 99%

“…Toyserkani et al conducted the first human pilot study of the use of ADSCs in lymphedema treatment [7]. They recruited 10 patients (median age, 55 years) with breast cancer-related lymphedema who received injections of ADSCs into the axillary region associated with a scarreleasing, fat-grafting procedure.…”

Section: Resultsmentioning

confidence: 99%

“…Still considered an incurable condition, lymphedema has challenged clinicians around the world to propose new treatment modalities [7]. In this scenario, imaging examinations that allow further assessment of lymphatic function, such as lymphoscintigraphy, could be useful to understand therapeutic responses [8].…”

Section: Introductionmentioning

confidence: 99%

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Lymphoscintigraphy for Evaluation of Lymphedema Treatment: A Systematic Review

Forte

Boczar

Huayllani

et al. 2019

Cureus

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Lymphoscintigraphy is a well-established radiologic examination to evaluate lymphatic function. We conducted a systematic review of the use of lymphoscintigraphy for evaluation of lymphedema treatment. We hypothesized that this radiologic examination could add relevant findings of treatment outcomes of lymphedema patients. We conducted a systematic review of articles in PubMed, without any time frame or language limitations, about the use of lymphoscintigraphy for the evaluation of lymphedema treatment. Articles were excluded if they investigated other uses of lymphoscintigraphy, such as diagnosis or prevention of lymphedema. Abstracts, presentations, reviews, and meta-analyses were also excluded. Of 101 potential articles found in the literature, 5 fulfilled our study eligibility criteria, and they were all case series. These articles included a total of 327 patients, most of whom had breast cancer-related lymphedema. Interventions included lymph node or vessel transfer (3 of 5 articles), complex decongestive therapy (1 of 5), and adipose-derived stem cell injection (1 of 5). The authors of these studies used lymphoscintigraphy to investigate the treatment functional outcomes, prognostic value, and complications. Lymphoscintigraphy detected lymphangiogenesis in transferred lymph nodes, and it was able to predict patient response to complex decongestive therapy. Studies that used lymphoscintigraphy to evaluate lymphedema treatment demonstrated its flexibility to provide various types of information. We hope this review will support future studies.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Lymphoscintigraphy for Evaluation of Lymphedema Treatment: A Systematic Review

Forte

Boczar

Huayllani

et al. 2019

Cureus

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“…MSC-Ex exert effects via delivering MSC-derived cargos (i.e., DNAs, mRNAs, miRNAs, and proteins) to host cells, which lead to changed behaviors of recipient cells to enhance tissue repair. (Liu, Lin et al, 2018, Mayourian, Ceholski et al, 2018, Valadi, Ekstrom et al, 2007 Thus, it will be necessary to determine the factors that control hucMSC-Ex mediated lymphangiogenesis and their antilymphedemic effects. So far antilymphedema studies have only used bone marrow MSC (BM-MSCs) and ADSCs.…”

Section: Introductionmentioning

confidence: 99%

“…So far antilymphedema studies have only used bone marrow MSC (BM-MSCs) and ADSCs. (Ackermann, Wettstein et al, 2015, Toyserkani, Jensen et al, 2018, Zhou et al, 2017 Human umbilical cord-derived MSCs (hucMSCs) are of interest in regenerative medicine because of their low cost, minimal invasiveness, and convenient isolation methods. (Bartolucci, Verdugo et al, 2017, Ding, Chang et al, 2015, Li, Xia et al, 2015 Thus, hucMSC-Ex may represent an ideal cell-free therapy for lymphedema.…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal stem cell derived exosomes enhance lymphangiogenesis via exosomal transfer of Ang-2/Tie2

Zhao

Zhang

Liu

et al. 2018

Preprint

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Mesenchymal stem cell derived exosomes (MSC-Ex) are nanosized membrane-bound extracellular vesicles found in MSC conditioned medium, that have yielded beneficial effects in several experimental models of organ injury. However, the therapeutic value and mechanism of MSC-Ex in lymphedema is poorly understood. Here we find that human umbilical cord MSCs derived exosomes (hucMSC-Ex) treatment contributed to the regeneration of LYVE-1 positive lymphatic vessels and reduction of lymphedema in a mouse model of tail lymphedema. Following uptake, exosomal lymphangiogenic factors (angiopoietin (Ang)-2 and Tie2) are taken up by HDLECs and promoted HDLECs proliferation, migration, and tube formation in vitro. We also find that exosomal Ang-2 and Tie2 exert a prolymphangiogenic effect on HDLECs through upregulating Prox1 and VEGFR3/p-Akt expression. In conclusion, our result unravel a previously unappreciated prolymphangiogenic role of hucMSC-Ex in lymphedema therapy and provide a new mechanism of Ang-2 in therapeutic lymphangiogenesis.

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Adipose-derived regenerative cells and lipotransfer in alleviating breast cancer-related lymphedema: An open-label phase I trial with 4 years of follow-up

Jørgensen

Toyserkani

Jensen

et al. 2021

Stem Cells Translational Medicine

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Patients with breast cancer-related lymphedema (BCRL) have reduced quality of life and arm function. Current treatments are palliative, and treatments improving lymphedema are lacking. Preclinical studies have suggested that adipose-derived regenerative cells (ADRCs) can alleviate lymphedema. We, therefore, aimed to assess whether ADRCs can alleviate lymphedema in clinical reality with long-term follow-up. We treated 10 patients with BCRL using ADRCs and a scar-releasing lipotransfer to the axillary region, and all patients were followed 1, 3, 6, 12, and 48 months after treatment. The primary endpoint was change in arm volume. Secondary endpoints were safety, change in lymphedema symptoms, quality of life, lymphedema-associated cellulitis, and conservative treatment use. There was no significant decrease in BCRL volume after treatment. However, self-reported upper extremity disability and arm heaviness and tension improved. Six patients reduced their use of conservative BCRL treatment. Five patients felt that their BCRL had improved substantially, and four of these would redo the treatment. We did not observe any cases of locoregional breast cancer recurrence. In this phase I study with 4 years of follow-up, axillary delivered ADRCs and lipotransfer were safe and feasible and improved BCRL symptoms and upper extremity function. Randomized controlled trials are needed to confirm the results of this study.

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Adipose-derived regenerative cells and fat grafting for treating breast cancer-related lymphedema: Lymphoscintigraphic evaluation with 1 year of follow-up

Cited by 26 publications

References 22 publications

Lymphoscintigraphy for Evaluation of Lymphedema Treatment: A Systematic Review

Lymphoscintigraphy for Evaluation of Lymphedema Treatment: A Systematic Review

Mesenchymal stem cell derived exosomes enhance lymphangiogenesis via exosomal transfer of Ang-2/Tie2

Adipose-derived regenerative cells and lipotransfer in alleviating breast cancer-related lymphedema: An open-label phase I trial with 4 years of follow-up

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