Gloria Sue, Dung Nguyen, Dimitris Dionysiou, Tatiana Zaitseva, Cristhian Montenegro, Peter Tabada, Peter Deptula, Derrick Wan, Nathan Katz, Michael Paukshto, Stanley Rockson.

Stanford University, Stanford, CA, US

Aristotle University of Thessaloniki, Greece

Fibralign Corp, Union City, CA, US 

Jointechlabs, San Francisco, CA, US

To address the current deficit of sustainable lymphedema treatment, we investigated lymphatic regeneration guided by thread-like aligned nanofibrillar collagen scaffolds (BioBridge), which facilitate cell attachment, alignment, and migration. In this study, we tested our hypothesis that implantation of BioBridge with seeded Adipose-Derived Stem Cells (ADSCs) can reduce lymphedema when used in animals with developed lymphedema.

The rat lymphedema model involved inguinal and popliteal lymphadenectomy followed by irradiation. Subjects that developed lymphedema one month after lymphadenectomy/irradiation either received implantation of BioBridge with allogeneic ADSCs (treatment group) or remain untreated (control group). All subjects were observed for 4 months after lymphadenectomy.  The change in affected to unaffected limb volume ratio was evaluated using CT-based volumetric analysis. Lymph flow and lymphangiogenesis were also assessed by ICG.

Subjects in the treatment group showed a reduction in affected limb volume (affected/non-affected limb volume ratio decreased from 113% to 97% (p <0.02)). ICG fluoroscopy demonstrated lymph flow and formation of lymphatics towards the contralateral groin in the direction of the implanted scaffolds. Conducted immunogistohistology supported the findings.

These data show that in the rat lymphedema model, the treatment of established lymphedema with BioBridge and ADSC substantially reduces lymphedema.

In preparation for a clinical application, we characterized human ADSC plated on BioBridge by FACS and compared manual ADSC isolation protocol with isolation using MiniStem system which is suitable for use in a clinical setting.