Tissue-engineered lymphatic graft for the treatment of lymphedema

Kanapathy, Muholan; Patel, Nikhil; Kalaskar, Deepak M.; Mosahebi, Afshin; Mehrara, Babak J.; Seifalian, Alexander M.

doi:10.1016/j.jss.2014.07.059

Cited by 23 publications

(27 citation statements)

References 98 publications

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“…Non-surgical therapies are time-consuming, associated with loss of quality of life, and cannot stop the disease or achieve a complete cure. Surgical methods are associated with donor site morbidities and often lead to poor outcomes [50]. To bypass the problem of harvesting own tissue, such as a lymph nodes, a range of tissue engineering approaches have been developed during recent years, such as coculturing of lymphatic endothelial cells with stem cells, developing hydrogels, and using growth factors or stimulation with interstitial flow [51].…”

Section: The Av Loop As a Tool To Generate A Multitude Of Different Tmentioning

confidence: 99%

The Arteriovenous Loop: Engineering of Axially Vascularized Tissue

et al. 2018

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Background: Most of the current treatment options for large-scale tissue defects represent a serious burden for the patients, are often not satisfying, and can be associated with significant side effects. Although major achievements have already been made in the field of tissue engineering, the clinical translation in case of extensive tissue defects is only in its early stages. The main challenge and reason for the failure of most tissue engineering approaches is the missing vascularization within large-scale transplants. Summary: The arteriovenous (AV) loop model is an in vivo tissue engineering strategy for generating axially vascularized tissues using the own body as a bioreactor. A superficial artery and vein are anastomosed to create an AV loop. This AV loop is placed into an implantation chamber for prevascularization of the chamber inside, e.g., a scaffold, cells, and growth factors. Subsequently, the generated tissue can be transplanted with its vascular axis into the defect site and anastomosed to the local vasculature. Since the blood supply of the growing tissue is based on the AV loop, it will be immediately perfused with blood in the recipient site leading to optimal healing conditions even in the case of poorly vascularized defects. Using this tissue engineering approach, a multitude of different axially vascularized tissues could be generated, such as bone, skeletal or heart muscle, or lymphatic tissues. Upscaling from the small animal AV loop model into a preclinical large animal model could pave the way for the first successful attempt in clinical application. Key Messages: The AV loop model is a powerful tool for the generation of different axially vascularized replacement tissues. Due to minimal donor site morbidity and the possibility to generate patient-specific tissues variable in type and size, this in vivo tissue engineering approach can be considered as a promising alternative therapy to current treatment options of large-scale defects.

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Section: The Av Loop As a Tool To Generate A Multitude Of Different Tmentioning

confidence: 99%

The Arteriovenous Loop: Engineering of Axially Vascularized Tissue

et al. 2018

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“…Currently, a supermicrosurgical approach is applied in patients with secondary lymphatic disease [7], including lymphatic bypass surgery and lymph node transfer with implantation of both lymph nodes and surrounding vasculature. The long-term outcome of this complex procedure is improved compared to previous surgical and non-surgical interventions.…”

Section: Strategies To Enhance Vascular Lymphatic Regenerationmentioning

confidence: 99%

“…The long-term outcome of this complex procedure is improved compared to previous surgical and non-surgical interventions. However, since these techniques can only be employed for early stage lymphedema, new treatments for patients suffering from severe lymphedema are still desperately needed [7]. With current knowledge in the field of RM and bioengineering, new techniques may be designed to regenerate lymphatic structures as a treatment for lymphedema.…”

Section: Strategies To Enhance Vascular Lymphatic Regenerationmentioning

confidence: 99%

“…With current knowledge in the field of RM and bioengineering, new techniques may be designed to regenerate lymphatic structures as a treatment for lymphedema. All in all, regeneration of pre-existing lymphatic vessels by stimulating lympangiogenesis, ex vivo engineering of lymphatic grafts and lymph nodes (ex vivo assembly) and in vivo development of new lymphatic structures (in situ assembly) can be addressed by RM approaches [7], [95]. However, due to its multiple anatomical and functional differences, a single approach for lymphatic RM seems unfeasible.…”

Section: Strategies To Enhance Vascular Lymphatic Regenerationmentioning

confidence: 99%

“…For example, 15% -60% of the patients with early stage lymphedema in the upper limb region do not experience improvement in limb volume after surgery [6] whereas treatments for patients with advanced lymphedema are lacking altogether [7]. New methods to prevent lymphedema or to regenerate lymphatics in damaged tissue will thus improve quality of life.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Lymphatic Vascular Regeneration: The Next Step in Tissue Engineering

Huethorst

Krebber

Fledderus

et al. 2016

Tissue Engineering Part B: Reviews

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The lymphatic system plays a crucial role in interstitial fluid drainage, lipid absorption, and immunological defense. Lymphatic dysfunction results in lymphedema, fluid accumulation, and swelling of soft tissues, as well as a potentially impaired immune response. Lymphedema significantly reduces quality of life of patients on a physical, mental, social, and economic basis. Current therapeutic approaches in treatment of lymphatic disease are limited. Over the last decades, great progress has been made in the development of therapeutic strategies to enhance vascular regeneration. These solutions to treat vascular disease may also be applicable in the treatment of lymphatic diseases. Comparison of the organogenic process and biological organization of the vascular and lymphatic systems and studies in the regulatory mechanisms involved in lymphangiogenesis and angiogenesis show many common features. In this study, we address the similarities between both transport systems, and focus in depth on the biology of lymphatic development. Based on the current advances in vascular regeneration, we propose different strategies for lymphatic tissue engineering that may be used for treatment of primary and secondary lymphedema.

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Construction of tissue‐engineered lymphatic vessel using human adipose derived stem cells differentiated lymphatic endothelial like cells and decellularized arterial scaffold: A preliminary study

Yang

Chen

et al. 2017

Biotech and App Biochem

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We have previously demonstrated that human adipose-derived stem cells (hADSCs) can be differentiated into lymphatic endothelial like cells. The purpose of this study was to investigate the feasibility of utilizing the induced lymphatic endothelial like cells and decellularized arterial scaffold to construct the tissue-engineered lymphatic vessel. The hADSCs were isolated from adipose tissue in healthy adults and were characterized the multilineage differentiation potential. Decellularized arterial scaffold was prepared using the Triton x-100 method. ADSCs were differentiated into lymphatic-like endothelial cells, and the induced cells were then seeded onto the decellularized arterial scaffold to engineer the lymphatic vessel. The histological analyses were performed to examine the endothelialized construct. The decellularized arterial scaffold was successfully obtained and was able to maintain its vessel morphology. The isolated ADSCs can be differentiated into osteocytes and adipocytes. After seeding onto the scaffold, the seeded cells attached and grew well on the decellularized arterial scaffold. Our preliminary results demonstrated that the induced lymphatic endothelial like cells combined with decellularized arterial scaffold could be utilized to successfully engineer the lymphatic vessel. Our findings may be helpful for the development of tissue-engineering of the lymphatic graft.

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Tissue-engineered lymphatic graft for the treatment of lymphedema

Cited by 23 publications

References 98 publications

The Arteriovenous Loop: Engineering of Axially Vascularized Tissue

The Arteriovenous Loop: Engineering of Axially Vascularized Tissue

Lymphatic Vascular Regeneration: The Next Step in Tissue Engineering

Construction of tissue‐engineered lymphatic vessel using human adipose derived stem cells differentiated lymphatic endothelial like cells and decellularized arterial scaffold: A preliminary study

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