13. Autologous Adipocyte Cell Therapy For Secondary Lymphedema
Year: 2024
Type: article
Abstract: Purpose: Secondary lymphedema is a chronic edematous condition associated with the methods to treat cancer leading to progressive swelling in extremities and chronic inflammatory response. Lymphedema is currently managed using physical approaches for early-stage lymphedema and surgical interventions like lymphovenous anastomosis for late-stage lymphedema. We hypothesize that an autologous adipocyte cell therapy expressing peptides to inhibit the pathogenesis will reduce fibroadipose tissue deposition. Here, we treat mice with a peptide inhibitor of the Bone morphogenetic protein (BMP) signaling, which has been shown to play an important role in development of adipose tissue and adipogenic differentiation. Methods: Adipocytes were isolated from mouse inguinal fat tissue using a mechanical method followed by electroporation with plasmids encoding peptide inhibitors of BMP (CMV-BMPR1AFc) as previously demonstrated by our lab. The mouse hind limb lymphedema model was induced by excision of the ipsilateral superficial, inguinal, popliteal, deep inguinal lymph nodes and femoral lymphatic vessel. The experimental cohort was subdivided into three groups with no treatment (n=8), electroporated adipocytes with no plasmid (n=8) and electroporated adipocytes with CMV-BMPR1AFc (n=8) and received injections (50µl S.C) in the ipsilateral hindlimb on day 3 post-surgery. All mice were sacrificed on day 7 and the tissues were harvested and stained with H&E and Picrosirius Red. Results: The fibroadipose tissue thickness decreased in CMV-BMPR1AFc treated mice in comparison to the other two groups. The edema and the hind limb circumference was relatively reduced after treatment with CMV-BMPR1AFc. The CMV-BMPR1AFc reduced the fibrotic tissue thickness (control:157.8 ± 45.3μm; lymphedema: 878.4 ± 206.8μm; plasmid control: 515.5 ± 45.3μm; CMV-BMPR1AFc: 316.5 ± 109.6μm; p<0.05), adipocyte hyperplasia (control: 39.25 ± 9.9 npf; lymphedema: 99.0 ± 30.4 npf; plasmid control: 61.25 ± 27.8 npf; CMV-BMPR1AFc: 45.9 ± 13.0 npf; p<0.05) and hypertrophy (control: 368.0 ± 151.4μm2; lymphedema: 772.9 ± 183.2μm2; plasmid control: 708.1 ± 240.7μm2; CMV-BMPR1AFc: 442.7 ± 168.9μm2; p<0.05) and normalized fibrosed area (control: 0.03 ± 0.01; lymphedema: 0.45 ± 0.15; plasmid control: 0.35 ± 0.07; CMV-BMPR1AFc: 0.18 ± 0.06; p<0.05). Conclusion: Our findings demonstrate that the electroporated adipocytes with the BMP inhibitor plasmid (CMV-BMPR1AFc) was able to reduce fibroadipose tissue deposition. Future studies will aim to study the long-term impact of the transfected adipocytes and inflammatory cascades with long term models of lymphedema.
Institution: Brigham and Women's Hospital
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,195
OpenAlex ID: W4394953541